We had an IT failure on Nov 7 for this event so it was postponed to Nov 14.
Practical Training
There is no cost to register for this activity.
Moderator(s):
Joshua Hayden, PhD, DABCC, FACB Norton Healthcare
Advanced Quantitative Mass Spectrometry Principles for Clinical Diagnostics: Session 2 : Part 1 Everything you wanted to know about Internal standards but were too afraid to ask
Russell Grant, PhD
Labcorp
Dr. Grant earned a first-class honors degree in Industrial Chemistry from Cardiff University and a PhD in Chromatographic and Mass Spectrometric technologies from the University of Swansea, Wales, United Kingdom. He continued his scientific training in various industrial settings, which have included senior scientist at GSK, Principal scientist at Cohesive Technologies, Technical director at Eli Lilly, and Director of Mass Spectrometry at Esoterix Endocrinology. Dr Grant is currently the Vice President of Research and Development and co-discipline director for Mass spectrometry at Labcorp. Dr Grant has pioneered the use of direct injection technologies, chromatographic systems multiplexing, microsampling, utility of automation, and other new analytical platforms in direct patient care. His research goals are focused upon improvements in speed, sensitivity, and quality of liquid chromatography with tandem mass spectrometric (LC-MS/MS) analytical systems and assays. Dr Grant has been awarded 100 patents and received both the MSACL Distinguished contribution award and ASMS AL Yergey “Unsung Hero” Award in 2024 for his contributions to Clinical Diagnostics using Mass Spectrometry.
One of the true killer applications in mass spectrometry involves the appropriate use of stable labelled internal standard materials to correct for a multitude of analytical variances. With great power, comes great responsibility (credit, Ben Parker in Spiderman). The second session will be given as two 90-minute linked vignettes and will explore established and novel approaches to definitively select and appropriately use internal standards, both in development and also into clinical utility, with the end goal of improving assay imprecision and error detection. The first module will describe in detail the "What, Why and How" Internal standards should be used in isotope dilution LC-MS/MS assays. The second session "But what about when?" will describe situations where Internal Standards fail criterion for use and how to correct deficiencies for effective LC-MS/MS assays. The third session will describe the "Unique capabilities" afforded to analytical measurement when used as internal calibrators/pre-analytic correction tools and in method development (as surrogates for analytes).
Take Home Pearls:
- How to rationalize and employ an internal standard in quantitative mass spectrometry
- How to use an internal standard to aid in assay development and as a troubleshooting tool
- How to creatively use stable labelled materials for quantification and historical calibration
Jacqueline Hubbard, PhD, DABCC Beth Israel Deaconess Medical Center, Harvard Medical School
LDT & the FDA - Will You be Ready? First Steps for 6 May 2025 Compliance at LC-MSMS CLIA Laboratories
Judy Stone, MT (ASCP), PhD, DABCC
Clinical Chemist (retired)
Judy Stone, MT (ASCP), PhD, DABCC has worked with LC-MS in diagnostic laboratories since 1999. Her clinical practice involved small molecule method development, instrument to instrument and instrument to LIS interfacing, LC-MS automation, monitoring quality of LC-MS methods in production and staff training for clinical LC-MSMS. She served as faculty chair for the 2009 AACC online certificate program “Using Mass Spectrometry in the Clinical Laboratory”, as a scientific committee member for the MSACL Practical Training track, and was editor-in-chief for the AACC Clinical Laboratory News quarterly feature series on Clinical LC-MS. She enjoys documenting and presenting esoteric as well as absurdly common LC-MS problems in creative ways in order to help trainees learn troubleshooting (and avoid repeating her mistakes).
The U.S. FDA Final Rule (6 May 2024) on Laboratory Developed Tests (LDT) is a concern for all CLIA laboratories performing LC-MSMS testing for patient care. The ACLA and AMP lawsuits, and Supreme Court “Chevron” ruling, have added uncertainty to the future for the Final Rule. But the first compliance deadline of 6 May, 2025, required for all LDTs, is on the horizon. Expert overviews of the LDT Final Rule are now available (recorded webinars) and more are planned by the FDA, ADLM, CLSI, and CAP. After 6 May 2024, MSACL formed a Compliance and Accreditation Committee (CAC). A primary committee goal is to support clinical LC-MSMS users who are planning their compliance with the U.S. FDA LDT Final Rule.
MSACL Connect, with MSACL-CAC Co-chairs Jacqueline Hubbard and Judith Stone, will present a webinar focusing specifically on in depth review and translation of regulatory to clinical laboratory language for the Complaints, Medical Device Reporting (MDR), Corrections and Removals requirements of LDT Final Rule compliance. These are the sections of the FDA’s four-year enforcement discretion phaseout that are due by 6 May 2025. Recommendations for an action plan and templates of SOPs/Forms/Logs designed to help laboratories customize their compliance for these requirements will be discussed. The document templates will be available for download to webinar attendees.
Jacqueline Hubbard, PhD, DABCC Beth Israel Deaconess Medical Center, Harvard Medical School
Advanced Quantitative Mass Spectrometry Principles for Clinical Diagnostics Session 1 : Part 2 How to Achieve Lower Quantification Limits
Russell Grant, PhD
Labcorp
Dr. Grant earned a first-class honors degree in Industrial Chemistry from Cardiff University and a PhD in Chromatographic and Mass Spectrometric technologies from the University of Swansea, Wales, United Kingdom. He continued his scientific training in various industrial settings, which have included senior scientist at GSK, Principal scientist at Cohesive Technologies, Technical director at Eli Lilly, and Director of Mass Spectrometry at Esoterix Endocrinology. Dr Grant is currently the Vice President of Research and Development and co-discipline director for Mass spectrometry at Labcorp. Dr Grant has pioneered the use of direct injection technologies, chromatographic systems multiplexing, microsampling, utility of automation, and other new analytical platforms in direct patient care. His research goals are focused upon improvements in speed, sensitivity, and quality of liquid chromatography with tandem mass spectrometric (LC-MS/MS) analytical systems and assays. Dr Grant has been awarded 100 patents and received both the MSACL Distinguished contribution award and ASMS AL Yergey “Unsung Hero” Award in 2024 for his contributions to Clinical Diagnostics using Mass Spectrometry.
Note: This is Part 2 of a two part session.
The first session will be given as two 90-minute linked vignettes and will explore established and novel approaches to definitively improve analytical measurement performance - with the end goal of improving an assay LLOQ. The answer isn't necessarily buy a newer mass spectrometer, it is attention to details and maximizing each step of the process. This one-hour session will be presented in three modules. The first module, Foundations, will focus on assessment and improvements to pipetting techniques, control of adsorptive losses and use of surrogate IS studies to assess imprecision reduction during assay development. The second module, Formulation, will focus on system cleanliness, the fallacy of S:N, LC system dead-volume and flow rate implications, ionization efficiency enhancements, source and optics fouling, the value of signal summing + scheduled MRM and quadrupole resolution settings.
The third module, Finesse, will tie these concepts and practical solutions together to demonstrate their use for assays that have been developed, validated and deployed. Particular focus will be made to detailed establishment of “on-column” amount, controlling adsorptive losses throughout the assay, 2D-LC to decouple selectivity and sensitivity variables, selectivity and stoichiometry of reagents in worst case specimens, the consideration that while counter counter-intuitive, more degrees of selectivity (analyte losses) may be optimal for an assay
Take Home Pearls:
- How to practically improve an assay performance as defined by lower levels of quantification
- How to enhance the throughput of an LC-MS/MS assay by paying attention to the little details
- How to enhance signal responses in a mass spectrometer without sacrificing quality"
Grace van der Gugten, B.Sc. Chemistry Alberta Precision Laboratories
Advanced Quantitative MS Principles for Clinical Diagnostics Session 1 : Part 1 How to Achieve Lower Quantification Limits
Russell Grant, PhD
Labcorp
Dr. Grant earned a first-class honors degree in Industrial Chemistry from Cardiff University and a PhD in Chromatographic and Mass Spectrometric technologies from the University of Swansea, Wales, United Kingdom. He continued his scientific training in various industrial settings, which have included senior scientist at GSK, Principal scientist at Cohesive Technologies, Technical director at Eli Lilly, and Director of Mass Spectrometry at Esoterix Endocrinology. Dr Grant is currently the Vice President of Research and Development and co-discipline director for Mass spectrometry at Labcorp. Dr Grant has pioneered the use of direct injection technologies, chromatographic systems multiplexing, microsampling, utility of automation, and other new analytical platforms in direct patient care. His research goals are focused upon improvements in speed, sensitivity, and quality of liquid chromatography with tandem mass spectrometric (LC-MS/MS) analytical systems and assays. Dr Grant has been awarded 100 patents and received both the MSACL Distinguished contribution award and ASMS AL Yergey “Unsung Hero” Award in 2024 for his contributions to Clinical Diagnostics using Mass Spectrometry.
The first session will be given as two 90-minute linked vignettes and will explore established and novel approaches to definitively improve analytical measurement performance - with the end goal of improving an assay LLOQ. The answer isn't necessarily buy a newer mass spectrometer, it is attention to details and maximizing each step of the process. This one-hour session will be presented in three modules. The first module, Foundations, will focus on assessment and improvements to pipetting techniques, control of adsorptive losses and use of surrogate IS studies to assess imprecision reduction during assay development. The second module, Formulation, will focus on system cleanliness, the fallacy of S:N, LC system dead-volume and flow rate implications, ionization efficiency enhancements, source and optics fouling, the value of signal summing + scheduled MRM and quadrupole resolution settings.
The third module, Finesse, will tie these concepts and practical solutions together to demonstrate their use for assays that have been developed, validated and deployed. Particular focus will be made to detailed establishment of “on-column” amount, controlling adsorptive losses throughout the assay, 2D-LC to decouple selectivity and sensitivity variables, selectivity and stoichiometry of reagents in worst case specimens, the consideration that while counter counter-intuitive, more degrees of selectivity (analyte losses) may be optimal for an assay.
Take Home Pearls:
- How to practically improve an assay performance as defined by lower levels of quantification
- How to enhance the throughput of an LC-MS/MS assay by paying attention to the little details
- How to enhance signal responses in a mass spectrometer without sacrificing quality"
How Mass Spectrometry Revolutionized Newborn Screening
David Millington, PhD
Duke University
David S. Millington, PhD, is Emeritus Professor of Pediatrics, recently retired from Duke School of Medicine. He and his colleagues pioneered the application of tandem mass spectrometry for the targeted analysis of acylcarnitines that became a frontline diagnostic test for defects of fat oxidation and branched-chain amino acid catabolism. Subsequently, the method was modified to include several essential amino acids and applied to dried blood spots, paving the way for the expansion of newborn screening for from a handful to over 30 metabolic conditions. As the expanded newborn screening method has spread, Dr. Millington has developed educational material and taught many laboratorians and follow-up coordinators worldwide how to apply the technology and interpret results. Expanded newborn screening by MS/MS is now applied to tens of millions of neonates annually and has help save thousands of lives. More recently, he has collaborated with a North Carolina biotechnology company to bring digital microfluidics into biochemical diagnostics and newborn screening. He has also pioneered novel biomarker assays for numerous lysosomal storage conditions to facilitate patient diagnosis and monitoring. Dr Millington has published over 200 research articles and book chapters and has served on the North Carolina Newborn Screening Program Advisory Board since 1990. He was honored jointly with Dr Mohamed Rashed by the ISNS with the Robert Guthrie award for outstanding contributions to newborn screening in 1996. He was also honored by the MSACL in 2015 with their first Distinguished Contribution Award in recognition of achievements made in the field of clinical mass spectrometry.
Mari DeMarco, PhD, DABCC, FACB, FCACB University of British Columbia
Can pre-clinical proteomics support therapy selection in precision medicine? A proof of
concept.
Philipp Lange, PhD
BC Children's Hospital, University of British Columbia
Dr. Philipp Lange is Canada Research Chair in Translational Proteogenomics of Pediatric Malignancies and Associate Professor of Pathology at the University of British Columbia (UBC). He is also a Scientist in the Michael Cuccione Childhood Cancer Research Program at the BC Children’s Hospital and the BC Cancer Research Institute.
Dr. Lange’s research focuses on precision oncology and oncoproteoforms, proteins with cancer-specific post-translational modification, their altered function, role in cell-cell communication and drug resistance, and their potential use as drug targets and biomarkers. His team drives the development and translation of proteomics platforms to advance molecular pathology and guide precision treatment for kids with cancer.
Dr. Lange provides leadership for Cancer Biology in the Canadian Pediatric Cancer Consortium ACCESS and co-leads the multi-centre proteomics team in the Canadian Precision Oncology For Young People (PROFYLE) study. He has won several awards for his advances in cancer research including the CIHR Early Career Investigator in Cancer Award and the Great Canadian Innovation Award by the Canadian Cancer Society.
Dr. Philipp Lange received his PhD in Biochemistry from the Free University Berlin, Germany after earning an MSc in Molecular Biology, Microbiology and Computer Sciences from the University of Hamburg, Germany. During his PhD with Dr. Dr. Thomas Jentsch at the Max Delbruck Centre for Molecular Medicine, Berlin, Germany he studied the molecular causes of hereditary osteopetrosis in children and patented a new drug target for the treatment of osteoporosis in adults. He conducted his postdoctoral work with Dr. Christopher Overall at the Centre for Blood Research, UBC developing computational and proteomics approaches to study post-translational modification in cancer.
Molecularly targeted precision treatments have significant potential to improve therapy options for hard-to-treat cancers and reduce late effects in general. Genome sequencing has laid the foundation for precision medicine, yet, clinical success remains moderate. Identifying therapeutic targets at the protein and pathway level by mass spectrometry-based proteomics holds great promise.
I will discuss analytical and systems challenges and propose possible strategies to smooth the path to full clinical translation. I will then present a proof of principle study in which we identified a possible treatment target in an adolescent with a recurrent rare malignancy. Within two weeks from biopsy, we conducted comprehensive DIA proteomics on H&E stained FFPE sections and validated a putative target by IHC. Following additional validation and failed chemotherapy and second line treatment the patient initiated a proteome guided monotherapy trial. I will then present an outlook how we envision to make pre-clinical proteome analysis and other innovative molecular pathology tests available to all children with cancer across Canada.
Co-organized with the Canadian National Proteomics Network.
Info on CNPN 2024.
Clinical metabolomics use cases to improve diagnosis and monitoring of endocrine disorders
Antonin Lamazière
Sorbonne Université
Antonin Lamazière is a professor and hospital practitioner at Sorbonne University's Faculty of Medicine. He heads the Hospital Department of Clinical Metabolomics at Hôpital Saint Antoine (AP-HP.Sorbonne Université).
His research interests lie at the interface between metabolism, nutrition and endocrine and metabolic pathologies. Through his work, he proposes translational approaches based on more fundamental pathophysiological issues, leading to the development of new diagnostic tools for use in healthcare. Recently, he and his team have highlighted the benefits of combining targeted metabolomic approaches with mathematical modeling based on machine learning and AI. The aims are both to map and better understand certain major biochemical pathways, and to envisage new endocrine semiologies to improve patient management and therapeutic follow-up.
With the performance of new devices, mass spectrometry now offers real opportunities in terms of diagnosis and therapeutic follow-up, particularly in the neuro-endocrine field. Through examples of routine clinical developments carried out in our clinical department, this presentation will show how gains in sensitivity and robustness enable us to access new endocrine semiologies with simultaneous assays of endogenous/exogenous steroid profiles in serum or on DBS, assays of somatotropic axis peptides or the use of mathematical models to develop digital medical devices.
This webinar will cover the following:
• Circulating steroid profiling improves management of PCOS syndrome
• Clinical applications of metabolomics DBS signatures
• High sensitivity 7500Qtrap enhances performances of proteomic biomarkers quantitation
Magali Wolff is the Head of Global Reagent Marketing and Support at Tecan. She has been with the
company since 2001. Magali and her team of product managers are dedicated to providing
laboratories with the best service and quality products for their daily workflows in specialty testing.
Fabian Reijn
Diagnotix
Fabian Reijn graduated in Chemistry from the University of Amsterdam as a bioanalytical chemist and has been involved in chromatography consultancy for 15 years, specializing in diagnostic applications. At Diagnotix, he serves as the Head of Sales, where he is primarily responsible for commercial tasks. In addition to his role, he provides training in chromatography/LC-MS, prepares new products and innovations, establishes strategic collaborations, and maintains continuous contact with the market.
In Vitro Diagnostic Regulation (IVDR) is the European Union’s new set of rules aimed at improving the quality, safety and reliability of IVDs. The new regulation is impacting the in vitro diagnostic landscape, affecting laboratories using their own “Laboratory Developed Tests” (LDTs) and those compliant with certain accreditation e.g. standard EN ISO 15189.
In this webinar you will learn:
What is IVDR and what are the timelines
What are the requirements for in-house tests (LDTs)
What are the next steps for your lab
Enhancing high-resolution mass spectrometry performance for NPS analysis with improved sensitivity and characterization
Pierre Negri, B.S, Ph.D
SCIEX
Pierre Negri is the global market development and marketing manager for the clinical and forensics market at SCIEX. In his current role, Pierre is responsible for driving the strategic growth of the global clinical and forensics market by implementing go-to-market strategy and brand awareness for critical applications. He is also leading global marketing campaigns to showcase the benefits of the solutions offered by SCIEX products in those spaces. Pierre came from the global technical marketing team, where he was previously responsible for generating technical content to support the global positioning of SCIEX products. In that role, Pierre was working closely with global key opinion leaders on novel applications of clinical and forensic mass spectrometry and developing relevant workflows highlighting the benefits of SCIEX solutions for specific applications. Pierre holds a Ph.D in analytical chemistry from the University of Georgia and a B.S degree in chemistry from the University of South Carolina, Aiken.
This presentation will introduce the instrument features on the ZenoTOF 7600 system that provide qualitative flexibility combined with quantitative power for NPS detection and characterization. The depth of information extracted from EAD-based MS/MS spectra combined with the improved MS/MS sensitivity were leveraged for characterization of structurally related isomeric species while providing detection of low-level potent NSO and metabolites in authentic case samples. The presentation will demonstrate that these new technological advancements on the system can be leveraged to provide more confidence in the quantified amounts of drugs and metabolites detected in discarded authentic case samples which is critical when determining the cause of death following an accidental overdose.
The Regulatory Landscape of Laboratory Developed Tests (LDT): A Laboratorian Perspective
Carmen Wiley, PhD, DABCC, FADLM
Incyte Diagnostics
Dr. Carmen Wiley was the 2019 - 2020 President of AACC. Recently she returned to the clinical practice of laboratory medicine and serves as Clinical Medical Director at Incyte Diagnostics. In this role, she supports the new clinical lab facility located in Spokane Valley and acts as the Medical Director over the clinical labs at Providence Sacred Heart Medical Center, Holy Family, My Carmel, and St. Joseph’s.
Dr. Wiley holds a Bachelor’s degree in Chemistry from the University of Minnesota, a Master’s degree in Organic Chemistry from the University of Washington, a Doctoral degree in Organic Chemistry from the University of Washington, and was a COMACC Accredited Fellow at the Mayo School of Medicine. She is board certified by American Board of Clinical Chemistry (ABCC) and a Fellow of the Academy of the American Association of Clinical Chemistry (FAACC).
Most recently, she was the Chief Medical Officer of a start-up company based in Oakdale, MN. Previously, she was a Regional Manager of Scientific Affairs – Cardiac at Roche Diagnostics. In this role, she was responsible for leading and developing the Medical & Scientific Liaisons in their relationships with the medical/scientific community, with the objective of critical scientific exchange including medical/scientific education. Dr. Wiley played a key role in providing support to healthcare professionals as well as internal Roche scientific groups and local business teams. Dr. Wiley was the Scientific Director at PAML where she was responsible for the medical and scientific oversight of all laboratory testing and oversaw all aspects of PAML’s research and development program. Prior to that, Dr. Wiley was Co-Director of Chemistry, Immunology, and Point of Care at Providence Health and Services, Sacred Heart Hospital in Spokane, WA and the Head of Clinical Chemistry in the Division of Laboratory Medicine and Pathology at the Marshfield Clinic in Marshfield, WI.
Dr. Wiley, her husband of 21 years and two kids enjoy time spent with their three dogs. She loves hiking, camping, and knitting. She is a native to Minnesota, but now considers Spokane, WA her home.
Stephen Master, MD, PhD, FADLM
Children's Hospital of Philadelphia
Stephen Master received his undergraduate degree in Molecular Biology from Princeton University, and subsequently obtained his MD and PhD from the University of Pennsylvania School of Medicine. After residency in Clinical Pathology at Penn, he stayed on as a faculty member with a research focus in mass spectrometry-based proteomics as well as extensive course development experience in bioinformatics. After time as an Associate Professor of Pathology and Laboratory Medicine at Weill Cornell Medicine in New York City, where he served as Director of the Central Lab and Chief of Clinical Chemistry Laboratory Services, he took a position at the Children's Hospital of Philadelphia at Chief of Lab Medicine. One of his current interests is in the applications of bioinformatics and machine learning for the development of clinical laboratory assays. He would play with R for fun even if he weren't getting paid, but he would appreciate it if you didn't tell that to his department chair.
The FDA released a proposed LDT rule and stated it will “end its enforcement discretion” of LDTs. Previously, the FDA explored other avenues for regulating LDTs. We will discuss questions relevant to the draft rule and implications to laboratory medicine, including, but not limited to:
What are possible implications of FDA regulation of LDTs?
Is the FDA the appropriate mechanism for this LDT oversight?
A New Chapter for Mitochondrial Testing: LC-MS/MS based Ketone Body Panel
Robin Kemperman, PhD
Children’s Hospital of Philadelphia
Robin Kemperman received his Bachelor's in chemistry from the HAN University of Applied Sciences in The Netherlands. Thereafter, he fulfilled his MSc and PhD in analytical chemistry at the University of Florida under the direction of Dr. Richard Yost. Currently, he works at the Children's Hospital of Philadelphia as Sr. Mass Spectrometrist in the Metabolic and Advanced Diagnostics Lab. Dr. Kemperman's work has covered a variety of aspects in mass spectrometry, including targeted analysis of steroids and ketone bodies using LC-MS/MS, bile acid, opioid, and glycan isomer separations using ion mobility spectrometry, and metabolomics High-Resolution MS. Dr. Kemperman is experienced in clinical MS-based validations and has presented his work at a variety of national and international meetings. Focusing on the future, he is interested in working on novel innovations for biomedical and clinical applications.
Rebecca Ganetzky, MD
Children's Hospital of Philadelphia and Perelman School of Medicine
Dr. Ganetzky runs a research group focused on understanding the biochemical sequelae of mitochondrial complex V deficiency. She is highly involved in metabolic training and leads the biochemical fellowships. She also sees patients with mitochondrial disease and other inborn errors of metabolism, with particular clinical interest in primary lactic acidosis, mitochondrial hepatopathy and disorders of pyruvate metabolism.
Inherited mitochondrial diseases can lead to disruptions in energy metabolism and abnormalities in the mitochondrial redox state because of impaired oxidation of NADH, the main reducing equivalent in the cell. As a result, the NADH/NAD+ ratio becomes elevated, which causes widespread secondary metabolic abnormalities in NAD+ utilizing pathways. Measuring the NADH/NAD+ ratio directly can be challenging due to its instability. However, there is a direct proportionality between the intramitochondrial NADH/NAD+ ratio and the ratio of the physiologic ketone bodies beta-hydroxybutyrate (BHB) and acetoacetate (AcAc). Therefore, assessing the ketone body ratio offers a more stable approach to estimate the mitochondrial redox state.
Measurement of the ketone body ratio is analytically challenging due to the instability of AcAc and the presence of BHB structural isomers like alpha-hydroxybutyrate (AHB), gamma-hydroxybutyrate (GHB), and beta-hydroxyisobutyrate (BHIB). Therefore, there was no clinically validated assay available to measure BHB, AcAc, and their ratio as a single test. Existing assays typically quantify AcAc and BHB separately using methods such as spectrophotometry, enzymology, or indirect measurements through gas chromatography. However, these methods often result in reduced accuracy of the ratio and require larger specimen quantities.
To enhance clinical care, a new rapid LC-MS/MS-based multiplex ketone body panel has been developed and clinically validated. This innovative panel only requires 10
Dan Blake is currently Senior Manager, Global Market Development & Marketing, Clinical, in the Strategic Marketing Team at SCIEX, responsible for the global clinical market & business. He has been at SCIEX for 20 years, working in several positions in application support & marketing, primarily within the clinical business. His main focus is around the market development and promotion of SCIEX’s technologies for use in clinical laboratories worldwide, showcasing how these technologies and solutions can improve research and understanding of the mechanisms of disease and develop new methodologies to improve laboratory medicine across the globe.
This webinar will discuss novel approaches to quantitation of molecules made possible by the new technologies offered by the SCIEX ZenoTOF 7600 system, and what this could potentially mean for the analysis of steroids and other challenging analytes.
We will present:
- An introduction to the SCIEX ZenoTOF 7600 system and the technologies and capabilities it offers
- Examples of how this can assist with challenges related to the analysis of steroids
- Wider examples in the field of quantitation of other challenging molecules such as lipids
Mari DeMarco, PhD, DABCC, FACB, FCACB University of British Columbia
The Michael S. Bereman Award for Innovative Clinical Proteomics : Translating Multiplexed Proteomic Assays to the Clinic and Beyond: Lessons from a Road Less Traveled
Timothy Collier, PhD
Quest Diagnostics
Dr. Timothy Collier is Scientific Director of Research & Development for the Quest Cardiometabolic Center of Excellence at Cleveland HeartLab, where his responsibilities include overseeing the identification and development of assays for cardiovascular biomarkers.
The process of translating mass spectrometry (MS)-based proteomic assays from basic research to the clinical laboratory remains a significant challenge for many laboratorians. The road to using innovative assays to aid in patient treatment is often fraught with obstacles, be they technical, financial, or regulatory. Over the past several years, our laboratory has had success in the research and development, validation, and commercialization of a multi-marker assay of high-density lipoprotein (HDL)
Oleg Karaduta, MD University of Arkansas for Medical Sciences
Olgica Trenchevska, PhD Cowper Sciences
The Metaproteomics Initiative: The cornerstone of the comprehensive molecular analysis of microbiome ecosystem.
Tim Van Den Bossche, PhD, MBA
Ghent University
Dr. Tim Van Den Bossche is currently working as postdoctoral researcher in the CompOmics lab of Prof. Lennart Martens in the field of microbial community proteomics, commonly known as metaproteomics. Here, he led the first-ever, community-driven, multi-site experiment that compared the effects of different state-of-the-art metaproteomics analysis pipelines (wet-lab and computational), and also compared the results with the taxa obtained from metagenomic and metatranscriptomic experiments - commonly known as the CAMPI study. With this momentum, he co-founded the Metaproteomics Initiative (www.metaproteomics.org) to further help accelerate the metaproteomics field. Next to this benchmark study and his work in the Initiative, he develops bioinformatics tools to metaproteomics data analysis.
Through connecting genomic and metabolic information, metaproteomics is an essential approach for understanding how microbiomes function in space and time. The international metaproteomics community is delighted to announce the launch of the Metaproteomics Initiative (www.metaproteomics.org), the goal of which is to promote dissemination of metaproteomics fundamentals, advancements, and applications through collaborative networking in microbiome research.
We will discuss past, present and future of this project as well as possible clinical implementations.
FeMS Happy Hour: A stigma around mental health in academia: where does it come from and what can we do?
Olya Vvedenskaya, MD, PhD
Lipotype, Dragonfly Mental Health
Academics are more likely to suffer from mental health disorders yet are less likely to seek treatment. Stigma is one of the highest ranked barriers to help-seeking for mental health problems. Sharing faculty stories is a powerful mechanism to reduce stigma, promote more open communication, and foster cultural change around mental health issues. Olya did her MD, PhD, and postdoc in translational medicine and mass spec. Currently she works as a scientific communications officer and devotes her spare time to academic mental health advocacy.
Mass spectrometry imaging at a million pixels per second and future clinical translation
Ian Anthony, PhD
Maastricht University
My research focuses on developing multimodal chemical instrumentation from a chemometric perspective, improving high spatial resolution mass spectrometry imaging capabilities, and applying semi-targeted complex mixture analysis methodologies. I'm interested in the development of new chemical imaging instrumentation because I see an increasing need for imaging instruments that produce high quality data that can can be easily interpreted by clinicians and applied scientists. To that end, I am working to build multimodal instruments, develop experiment methodologies, and create data analysis pipelines that are able to produce higher-quality chemical information more rapidly and with fewer steps than existing imaging instruments and workflows.
Most mass spectrometry imaging (MSI) is performed one pixel at a time at a rate below 1,000 pixels per second. Recently, researchers at the M4i institute at Maastricht University developed an MSI technique called fast mass microscopy [1] which acquires many mass spectra in parallel and is capable of imaging at over 1 million pixels per second. This improvement of >1,000 times imaging speed opens new opportunities for MSI in clinical applications as experiments that would otherwise take months can now be done in less than an hour. This seminar will focus on fast mass microscopy and strategies for its future clinical translation.
Ólöf Gerður Ísberg, MSc, PhD Vanderbilt University, MSACL Early Career Network
Grant Writing for Beginners
Kristine Glunde, Ph.D., M.S.
The Johns Hopkins University School of Medicine
Dr. Glunde is Professor of Radiology, Oncology and Biological Chemistry at The Johns Hopkins University School of Medicine, and the founding Director of the Applied Imaging Mass Spectrometry (AIMS) Core. Her research program focuses on cancer biology and molecular imaging of cancer. Her lab combines molecular biology and cancer biology approaches with multi-scale molecular imaging to investigate and visualize molecular events that drive cancer growth, invasion, and metastasis. Imaging technologies used in Dr. Glunde's lab span magnetic resonance imaging, magnetic resonance spectroscopic imaging, mass spectrometry imaging, and optical and fluorescence imaging. Dr. Glunde has mentored more than 50 students, post- doctoral fellows, and junior faculty and has published over 100 publications in the field of cancer metabolism and molecular imaging of cancer. She has received many competitive grants from the National Institutes of Health (NIH) and frequently serves on NIH study sections and grant review panels of other funding agencies. Dr. Glunde founded the AIMS Core in 2019, making available highly multiplexed, high throughput mass spectrometry imaging technology to faculty at Johns Hopkins and outside institutions. She has built a quickly expanding mass spectrometry imaging program at Johns Hopkins, where her team interacts with a diverse group of over 55 users, spanning multiple departments at Johns Hopkins and several institutions nationwide.
Berta Cillero-Pastor, PhD
Maastricht University
Dr. Cillero-Pastor studied molecular biology and biochemistry at the Autonomous University of Madrid, Spain. In 2009 she obtained her PhD at the INIBIC Institute of La Coruna (cum laude) after having been awarded a fellowship from the Carlos III Health Institute (Spain) to study the effect of pro-inflammatory cytokines in diseased cartilage by proteomics. In 2010 and after having obtained an Angeles Alvarino fellowship, she moved to Amsterdam to work as postdoctoral researcher at Ron Heeren´s lab, AMOLF. In that period, she developed new mass spectrometry imaging approaches in the field of orthopaedics. In 2015 she joined Maastricht University as CORE lab leader at the division of Imaging Mass Spectrometry (M4i). Since then, she has established her own research line on the application of mass spectrometry imaging and proteomics for different biomedical applications with special focus on cardiovascular research and musculoskeletal diseases. She has received funding from NWO and Horizon 2020, including several European ITN grants.
She is principal investigator at the MERLN institute, Maastricht University, since March 2022. Her group develops new spatial omics approaches to understand cell-biomaterial interactions, local drug delivery, biofilm formation, and molecular mechanisms of cell differentiation.
If you are a new researcher, wondering how to be successful in receiving grants from sources such as National Institutes of Health (NIH) or Marie Curie- ITN , join us for this session with experienced panelists. It will be interesting to hear the grant writing stories
from two people working in two different parts of the world.
The session will provide resources and insights on finding grant applications, hot topics to write on, quantity v/s quality of grants, general advice and much more.
Translating global metabolomics into clinical applications
Liang Li, PhD
Metabolomics Innovation Centre of Canada & University of Alberta
Dr. Li obtained his B.Sc. degree in Chemistry from Zhejiang (Hangzhou) University, China, in 1983, and his Ph.D. degree in Chemistry from the University of Michigan, Ann Arbor, USA, in 1989, under the direction of Professor David M. Lubman. After graduation, he joined the Department of Chemistry at the University of Alberta, Edmonton, Alberta in July 1989. He was an Assistant Professor from 1989 to 1994 and an Associate Professor from 1994 to 1999. He has been a Full Professor since July 1999. He has also been an Adjunct Professor of Biochemistry Department, Faculty of Medicine, since January 2008. He holds a Visiting Professorship at Zhejiang University supported by K. P. Chao’s Hi-Tech Foundation for Scholars and Scientists since 2006. He is a co-PI of The Metabolomics Innovation Centre (TMIC) mainly supported by Genome Canada. He was a co-PI of the Human Metabolome Database (HMDB) Project; his laboratory generated the HMDB MS/MS spectral library of the endogenous human metabolites that has been widely used by the metabolomics community for unknown metabolite identification based on spectral matches. Dr. Li was a visiting scientist at Hewlett Packard Research Lab (now Agilent), Palo Alto, CA (on sabbatical leave) from July 1998 to June 1999. He served as Director, Alberta Cancer Board Proteomics Resource Lab from February 2000 to December 2005. He served as Chair, Analytical Chemistry Division of Chemistry Department from July 2007 to June 2019. He serves as a Co-Director of TMIC since July 2019. He is a founder of Nova Medical Testing, Inc., a university spin-off company focusing on developing mass spectrometry based analytical solutions for medical and health diagnostic applications, including targeted diagnostic-panel analysis and global biomarker analysis.
Dr. Li is an elected fellow of the Royal Society of Canada (Academy of Science) (2019) (watch this video on Youtube). He is a Canada Research Chair in Analytical Chemistry (Tier 1, 2005-2012; renewed for 2012-2019). He has won several awards including McBryde Medal (2001) from the Canadian Society for Chemistry, Faculty of Science Outstanding Research Award (2002), McCalla Professorship (2002-2003), and Killam Annual Professorship (2004-2005) from the University of Alberta. He received the Young Explorers Prize from the Canadian Institute for Advanced Research (CIAR), which was given to Canada’s top twenty researchers aged forty or under in science and engineering (2002) as chosen by a panel of international judges. He was the recipient of the Rutherford Memorial Medal in Chemistry from the Royal Society of Canada (2003). He received The F.P. Lossing Award from the Canadian Society for Mass Spectrometry in 2006, The Maxxam Award from the Canadian Society for Chemistry in 2009 and Gerhard Herzberg Award from the Canadian Society for Analytical Sciences and Spectroscopy in 2010. He was one of the seven researchers selected as Brightest Minds 2016 by Canadian Institutes of Health Research. He is a fellow of the Chemical Institute of Canada since 2001.
Dr. Li has published more than 300 research papers mainly in the area of analytical mass spectrometry. He has given many invited talks including Hong Kong Polytechic University Distinguished Lecture in 2011, Distinguished Lectureship on Cerebrating the 50th Anniversary of Hong Kong Baptist University Faculty of Science in 2011, and Thermo Fisher Scientific Distinguished Scientist Lecture at the University of Montreal in 2013.
Dr. Li is currently an editor of Analytica Chimica Acta, an international journal on analytical chemistry with an Impact Factor of 6.558 in 2020 (2005-present). He is a member of the editorial advisory boards for Current Analytical Chemistry (2004-present), Journal of Advanced Research (Elsevier) (2014-), Biophysics Reports (Springer) (2015-), and Chemical Data Collections (Elsevier) (2015-). Dr. Li was a member of the editorial advisory boards for Journal of the American Society for Mass Spectrometry (2001-2006), Canadian Journal of Chemistry (2004-2006), Clinical Proteomics (2011-2016), and Analytical Chemistry Insights (2006-2018). He was a member of Analytical Chemistry’s A-Page Advisory Panel (2006-2008).
Metabolomics is a relatively newcomer of the Omics family for large-scale characterization of small molecules of biological systems. A key step in metabolomics is to determine metabolic differences among different samples. We want to detect and quantify as many metabolites as possible, ideally covering the entire chemical space of the metabolome. High-coverage metabolome analysis will benefit many research areas, including disease biomarker discovery, population-based health analytics and clinical applications. This presentation will focus on the discussion of current challenges and potential solutions for translating global metabolomics into clinical applications.
Ólöf Gerður Ísberg, MSc, PhD Vanderbilt University, MSACL Early Career Network
Effective use of PowerPoint for scientific presentations
Ian Anthony, PhD
Maastricht University
My research focuses on developing multimodal chemical instrumentation from a chemometric perspective, improving high spatial resolution mass spectrometry imaging capabilities, and applying semi-targeted complex mixture analysis methodologies. I'm interested in the development of new chemical imaging instrumentation because I see an increasing need for imaging instruments that produce high quality data that can can be easily interpreted by clinicians and applied scientists. To that end, I am working to build multimodal instruments, develop experiment methodologies, and create data analysis pipelines that are able to produce higher-quality chemical information more rapidly and with fewer steps than existing imaging instruments and workflows.
Even the most impactful research such as curing cancer and solving nuclear fusion is useless unless it is communicated. At some point, most science is communicated through presentations and, for better or worse, Microsoft PowerPoint is the gold-standard for slide-based presentations. Knowing how to make effective, high-quality PowerPoint presentations quickly will increase your ability to transfer knowledge, free up your time, and increase your impact. In this interactive MSACL event, you will learn theories of slide design, effective use of visual aids, and assorted
Josh Learns Billing: how to bill urine toxicology so you actually get paid
Joshua Hayden, PhD, DABCC, FACB
Norton Healthcare
Joshua is currently the Chief of Chemistry at NortonHealthcare. He earned his PhD in chemistry from Carnegie Mellon University. He conducted postdoctoral research at Massachusetts Institute of Technology before completing a two-year clinical chemistry fellowship at University of Washington and 4 years as Assistant Professor at Weill Medical College. Joshua has special expertise developing and overseeing mass spectrometry assays in the clinical laboratory.
Setting up a clinical mass spectrometry lab presents a host of challenges with a great deal of attention understandably paid to developing and validating high quality assays. Rarely do laboratorians consider the reimbursement aspect of the testing they are setting up. This is unfortunate given the importance financial success has in determining whether or not an organization will invest in such testing. Reimbursement and appropriate billing is especially important to consider when it comes to more complex testing such as urine toxicology; appropriate billing of this testing is essential to ensure labs get adequately reimbursed and stay in compliance with applicable laws and regulations. This CONNECT webinar will focus on lessons learned establishing urine toxicology testing from the billing aspect. It will include an overview of how such testing should be billed, mistakes that are often made when establishing such testing, and the tools available to labs to help ensure testing is properly billed (and more likely reimbursed). Ample time will be given to ensure the audience can share their own struggles in this area and can ask questions about the topics raised.
View recordings of Josh's series on Getting going with Mass Spectrometry - his real time journey of setting up Mass Spec testing in a Clinical Lab.
Archived FFPE tissues for MS based disease biomarker discovery? Not as incompatible as one may think.
Prof Peter Verhaert, PhD
ProteoFormiX
Peter VERHAERT was full professor Analytical Biotechnology and Innovative Peptide Biology at Delft University of Technology [Netherlands; 2005 – 2016] before founding his company ProteoFormiX (www.proteoformix.com). His Flemish research startup is alumnus of JLABS, the J&J Innovation Center, and was born at JLABS@BE on the Campus of Janssen Pharmaceuticals in Beerse [Belgium; 2017].
Peter is recognized worldwide as one of the pioneers in Peptidomics, Peptides in Biology being the common theme in his >35 years of research.
Prior to taking up his academic position in Delft and ultimately starting his own research company in Beerse, Peter's international career already combined academic and industrial positions:
He obtained an MSc in Biology (Zoology Group) and a PhD in Comparative Neurobiology at the University of Leuven, where he held a position as assistant professor [Belgium; 1983-1987].
He then took on a postdoc position at the Laboratory of Toxicology and Biochemistry in the Biology Department of the University of Waterloo [Canada; 1988].
Upon returning to the University of Leuven, he became an associate professor in Histology and Biological Mass Spectrometry [Belgium; 1988-1999].
After an industrial sabbat year at the Flemish Biotech Innogenetics in Ghent [Belgium; 1998-1999], Peter was appointed group leader Proteomics at the Dutch Pharma company Organon (now MSD) in Oss [Netherlands; 2000-2004].
His other professional activities include:
• Co-founder and president of the European Pharmaceutical Proteomics Laboratories (EPPL) [2000-2004];
• Proteomics expert at the Flemish Institute of Biotechnology (VIB) [2000-2004];
• Visiting professor Biomedical Proteomics at the Biomedical Research Institute at the Faculty of Medicine of Hasselt University [Belgium; 2004-2014];
• Editor-in-chief of the Elsevier Open Access Journal EuPA Open Proteomics [2013-2016]
• Co-director of the Center of Excellence in Biomedical Mass Spectrometry (CEBMMS) at the Faculty of Medicine (Clinical Sciences Department) of Lund University [Sweden; 2016];
• Honorary professor Mass Spectrometry Histochemistry at the Maastricht Multimodal Molecular Imaging Institute (M4i) of Maastricht University [Netherlands; 2017-].
The lack of biomarkers still prevents the discovery and development of therapeutics and diagnostics for several serious diseases. Some of the latter can only be correctly diagnosed under the microscope by scrutinizing tissue sections of biopsy or even autopsy material.
Histopathologists all over the globe archive precisely annotated samples preferably in FFPE (formaldehyde-fixed paraffin-embedded) tissue banks. These represent a virtually unlimited resource of accurately diagnosed and stratified patients of all (stages of) diseases, which unfortunately today remains largely underexplored in biomarker research.
What if there would be a molecular discovery technology that could detect and identify biomarker candidates from the very same FFPE tissue sections?
What if this would be a label-free multiplex technology?
What if this technology would work on material stored for decades?
What if this technology could be spatially resolved?
What if this technology could generate molecule specific images that can be overlaid with other imaging modalities?
What if this technology would have single cell resolution in combination with single cell sensitivity?
What if this technology could localize molecules which are specifically produced and released from cells?
What if this technology would be multi-omics?
In this webinar I will argue that a technology already exists today that appears to combine all of the above.
Mass spectrometry histochemistry (MSHC), which combines atmospheric pressure MALDI with high resolution top-down MS, deserves this extra attention, as it may be(come) a welcome complement (or even alternative) to current LC-MS/MS biomarker discovery strategies that analyze extracts of tissues and body fluids.
Supported by an Open Unrestricted Educational Grant
provided by
There is no cost to register for this activity.
Should I report that?? Dealing with Unexpected Results in Clinical LC-MS/MS Testing
Joshua Hayden, PhD, DABCC, FACB
Norton Healthcare
Joshua is currently the Chief of Chemistry at NortonHealthcare. He earned his PhD in chemistry from Carnegie Mellon University. He conducted postdoctoral research at Massachusetts Institute of Technology before completing a two-year clinical chemistry fellowship at University of Washington and 4 years as Assistant Professor at Weill Medical College. Joshua has special expertise developing and overseeing mass spectrometry assays in the clinical laboratory.
Hsuan-Chieh (Joyce) Liao, PhD, DABCC, FADLM
University of Washington
Dr. Joyce Liao has more than ten years of clinical and management experience in laboratory medicine. She was a medical laboratory scientist in the newborn screening lab and obtained her Ph.D. degree in Clinical Medicine. She completed postdoctoral fellowship training in Clinical Chemistry at the University of Washington and Seattle Children’s Hospital. She is a board-certified Clinical Chemist and now serves as an Associate Director at Harborview Medical Center, focusing on toxicology and mass spectrometry testing. She continues to focus on the translation of the analytical power of mass spectrometry to real clinical applications. Her interests include toxicology, mass spectrometry, and laboratory utilization.
Heather Stieglitz, PhD, DABCC
The Ohio State University Wexner Medical Center
Dr. Stieglitz is currently an Assistant Professor at The Ohio State University Wexner Medical center and Co-Director of Clinical Chemistry and Toxicology. She received her PhD from Emory University and completed a postdoctoral fellowship in Clinical Chemistry at the University of North Carolina before joining Ohio State. She is board certified in Clinical Chemistry by the American Board of Clinical Chemistry. Her interests are in mass spectrometry-based clinical toxicology testing in adults and newborns.
Once live with mass spectrometry-based testing, clinical laboratories face the challenge of ensuring adequate data review and accurate resulting. Inevitably, labs will encounter patient results that raise the question - should I report this? This interactive discussion will attempt to address issues related to questionable patient results including those with (i) unknown interferences that might impact the accuracy of the results, (ii) low internal standard recovery, and (iii) potential carryover. The discussion will be led by three individuals currently overseeing clinical toxicology mass spectrometry testing. Examples of challenges they have faced and (occasionally) approaches they have found useful will be presented as a starting point for discussion.
Supported by an Open Unrestricted Educational Grant
provided by
There is no cost to register for this activity.
The Application of LC-MS Fueling the Next Phase of Precision Medicine
Jennifer Van Eyk, PhD
Cedars-Sinai Heart Institute
Jennifer Van Eyk, PhD, is an international leader in the area of clinical proteomics and her lab has focused on developing technical pipelines for de novo discovery and larger scale quantitative mass spectrometry methods. This includes multiple reaction monitoring (MRM, also known as SRM) and most recently data independent acquisition. Dr. Van Eyk's laboratory is well known for the extreme technical quality of the data generated, rigorous quality control with tight %CV while applying these to key clinical questions. The aim is to maximize throughput and reproducibility in order to move targeted and robust discovery methods into large population healthy continuous assessment and clinical grade assays focusing on brain and cardiovascular diseases.
The throughput and reproducibility of LC-MS has facilitated the development of biologically important protein assays that are facilitating precision medicine adoption.
The Michael S. Bereman Award for Innovative Clinical Proteomics : Seeing the Forest for the Trees: Taking a Step Back to Move Proteomics Forward in the Clinical Lab
Mari DeMarco, PhD, DABCC, FACB, FCACB
University of British Columbia
Mari DeMarco, PhD, DABCC, FCACB, is a Clinical Chemist at Providence Health Care, the Research Director of Providence Research, and a Clinical Associate Professor in Pathology and Laboratory Medicine at the University of British Columbia in Vancouver Canada. Dr. DeMarco completed her PhD in the Biomolecular Structure and Design program at the University of Washington, and a clinical chemistry fellowship at Washington University School of Medicine.
With a strong interest in bridging basic biomedical science, analytical chemistry and laboratory medicine, Dr. DeMarco’s research group focuses on building new biofluid tests for direct translation into patient care. A particular area of interest is advancing protein-based clinical diagnostics for neurodegenerative disorders, such as Alzheimer’s disease. The goal of this program of research is to ensure that these new tools make the challenging jump from research into healthcare.
Originally Presented at MSACL 2022.
Want to run a new test in your clinical lab that takes multiple days to prep, has a complicated (and costly) calibration scheme, and a detection approach so selective it could miss the analyte of interest? If that doesn
Beyond the Human Genome: A Million Person Precision Population Health Project
Leroy Hood, MD, PhD
Institute for Systems Biology
Leroy "Lee" Edward Hood is an American biologist who has served on the faculties at the California Institute of Technology (Caltech) and the University of Washington. He is currently Professor and Chrief Strategy OFficer at the Institute for Systems Biology. Dr Hood has developed ground-breaking scientific instruments which made possible major advances in the biological sciences and the medical sciences. These include the first gas phase protein sequencer (1982), for determining the sequence of amino acids in a given protein; a DNA synthesizer (1983), to synthesize short sections of DNA; a peptide synthesizer (1984), to combine amino acids into longer peptides and short proteins; the first automated DNA sequencer (1986), to identify the order of nucleotides in DNA; ink-jet oligonucleotide technology for synthesizing DNA and nanostring technology for analyzing single molecules of DNA and RNA.
Dr Hood believes that a combination of big data and systems biology has the potential to revolutionize healthcare and create a proactive medical approach focused on maximizing the wellness of the individual. He coined the term "P4 medicine" in 2003.
The vision of this project is that we will develop the infrastructure to employ a data-driven approach to optimizing the health trajectory of individuals for body and brain. We have two large populations (5,000 and 10,000) that have validated this approach for body and brain health, respectively. These studies have led to us pioneering the science of wellness and prevention. This project will require the acquisition of key partners for execution, which will be delineated. We are approaching the Federal Government for funding, as we did for the first Human Genome Project. This project will lead to striking new knowledge about medicine, it will catalyze the initiation of start-up companies and it will catalyze a paradigm shift in healthcare from a disease orientation to a wellness and prevention orientation. This will catalyze the largest paradigm shift in medicine, ever.
Supervised Machine Learning for Mass Spectrometry Data Analysis: Experts' Opinion
Edward Lee, MD, PhD
Yale
Dr. Lee is a clinical pathology resident in the Department of Laboratory Medicine at Yale School of Medicine. He received his MD from the Albert Einstein College of Medicine and his PhD in Immunology from the University of Glasgow, where he conducted research in T cell receptor sequencing and mathematical modeling of T cell dynamics. His current research interests include developing computational approaches for analyzing high-throughput single-cell B cell and T cell repertoire profiling data and understanding the immunological mechanisms of alloimmunization to red blood cell antigens. He also involved in projects applying machine learning techniques to clinical laboratory data. He will be staying at Yale for his transfusion medicine fellowship and postdoctoral research fellowship.
Thomas Durant, MD
Yale
Dr. Durant is an Assistant Professor of Laboratory Medicine and informatics researcher at the Yale School of Medicine. He is the medical Director of Chemical Pathology and Laboratory Information Technology (IT) at Yale-New Haven Hospital, and the Associate Director for the ACGME Chemical Pathology Fellowship. He conducts applied laboratory medicine research with a pragmatic focus on quality care initiatives, laboratory outcomes, statistics, machine learning, and artificial intelligence applications in the context of pathology and clinical medicine. His primary research interests are in clinical informatics and using novel data management technology to better derive insight into the quality and overall operations for laboratories and patient care. Ongoing projects involve the investigation of stream processing of interface data for the purposes of automated sample identification for subsequent biobanking. Machine learning related projects include the use of 'very deep' convolutional neural networks for automated classification of digital images acquired in the clinical laboratory.
We will be talking with Thomas Durant and Edward Lee about recent advances in machine learning (ML) for mass spectrometry (MS) data analysis. The primary focus will be the alignment of these two fields (ML and MS) and how this offers a promising synergy that can be used to optimize workflows, improve result quality, and enhance our understanding of high-dimensional datasets, as well as their inherent relationship with disease biology. We will also dig deeper to understand a basic overview of ML and an ML-based experiment. Overall, we will have a opportunity go through the fundamental principles of supervised ML, outline the steps that are classically involved in an ML-based experiment, and discuss the purpose of good ML practice in the context of a binary MS classification problem.
Making Scientific Graphics with Open Source Software
Ian Anthony, PhD
Maastricht University
My research focuses on developing multimodal chemical instrumentation from a chemometric perspective, improving high spatial resolution mass spectrometry imaging capabilities, and applying semi-targeted complex mixture analysis methodologies. I'm interested in the development of new chemical imaging instrumentation because I see an increasing need for imaging instruments that produce high quality data that can can be easily interpreted by clinicians and applied scientists. To that end, I am working to build multimodal instruments, develop experiment methodologies, and create data analysis pipelines that are able to produce higher-quality chemical information more rapidly and with fewer steps than existing imaging instruments and workflows.
Graphics are what grab attention at your poster, what people see when they skim your paper, and what they remember from your presentation. Although it is possible to create professional quality graphics using a variety of approaches and software, there are only a few that provide flexibility to be useful across all scientific disciplines. Many of these are expensive, are not available on all popular operating systems, or use proprietary file formats. In this interactive MSACL Early Career Network event, you will learn how to use free and open source graphics software, specifically Inkscape and GIMP, to produce high quality scientific graphics that meet scientific journal requirements. We will cover (1) importing and saving different graphic file formats; (2) recoloring, cropping, and layering raster graphics; (3) editing and annotating plots; (4) creation of simple scientific workflow diagrams and schematics, and (5) assorted software
MS Proteotyping of Human Cancers in Oncology Therapeutic Development
Daniel C. Liebler, Ph.D.
Protypia, Inc.
Daniel C. Liebler, Ph.D. is an internationally-recognized research leader in the fields of proteomics, cancer proteogenomics, chemical biology and toxicology. With over 30 years experience at the interface of analytical technology, chemical biology and disease research, Dr. Liebler led multidisciplinary programs at the University of Arizona and Vanderbilt University School of Medicine funded by the National Institutes of Health, industry and private philanthropy. At Vanderbilt, Dr. Liebler's team laid the groundwork for the integration of proteomic technologies into cancer therapeutics and diagnostics. Dr. Liebler left Vanderbilt in 2016 to launch Protypia, which provides drug target and system analysis to leading pharmaceutical and biotechnology companies in therapeutic development.
In this discussion, Dr. Dan Liebler, President of Protypia, Inc., will highlight his research on MS proteotyping of human cancers in oncology therapeutic development using mass spectrometry.
Quantitative Analysis of the TIGIT/DNAM1 and PD-1/PD-L1 Axes in Primary Non-Small Cell Lung Cancers (NSCLC) and Lymph Node Metastases
Matt Westfall1, Salisha Hill1, Ryan D. Morrison1, Daniel C. Liebler1*, and Alexander Haragan2*
1 Protypia, Inc, Nashville, TN, USA
2 Royal Liverpool University Hospital, Department of Pathology, Liverpool, UK
New therapies targeting immune checkpoint (IC) proteins have revolutionized oncology therapeutics, but heterogeneous expression of IC proteins between individuals and tumor types complicates development of cancer immunotherapies. Although typically framed in the context of companion diagnostics, the need to reliably quantify drug targets is critical in the preclinical and clinical development of new drugs, especially for the design and interpretation of clinical trials. Quantification of drug target status can inform interpretation of target abundance and outcomes. Targeted mass spectrometry (MS) uniquely enables sensitive and precise measurement of IC proteins, coregulators and immune cell markers. MS measurements can be performed in formalin-fixed, paraffin-embedded (FFPE) samples and are multiplexed, thereby enabling simultaneous analysis of multiple IC proteins, immune cell markers, and related pathway markers in the same sample.
New immunotherapeutics targeting the IC protein TIGIT are in clinical development with PD-1/PD-L1 inhibitors for solid tumor indications, but without reliable TIGIT protein biomarkers to guide trial design and interpretation. We used targeted mass spectrometry (MS) to precisely quantify TIGIT, DNAM1, PVR, PVRL2, PD-1, PD-L1, and PD-L2 in 97 primary non-small cell lung cancers (NSCLC) and matched tumor draining lymph node metastases (TDLN). Only 56% of NSCLC cases expressed TIGIT, which was quantifiable almost exclusively in TDLN. TIGIT, DNAM1 and PVR abundance varied over approximately 25-fold and they were co-expressed only in some tumors. PD-1/PD-L1 axis proteins were quantified in virtually all samples over an even broader abundance range than TIGIT/DNAM1 axis proteins. Combined quantitation of TIGIT/DNAM1 and PD-1/PD-L1 axis proteins may indicate the sufficiency of the target system to respond to combined anti-TIGIT anti-PD-1/PD-L1 therapeutics.
Amanda Hummon earned her A.B. in chemistry at Cornell University in 1999 with honors. She completed her graduate studies in analytical chemistry at the University of Illinois, Urbana-Champaign, in the laboratory of Prof. Jonathan V. Sweedler. Her thesis work focused on the development of mass spectrometric and bioinformatic strategies to predict and identify neuropeptides. She received her Ph.D. in 2004. Amanda participated in the annotation of the newly sequenced honey bee genome as a post-doctoral fellow in the laboratories of Prof. Gene E. Robinson and Prof. Sandra L. Rodriguez-Zas at the University of Illinois from 2004-2005. The focus of her research was constructing a methodology to utilize detected gene products to decipher an unannotated genome.
From 2005-2009, Amanda was a Sallie Rosen Kaplen Post-Doctoral Fellow at the National Cancer Institute in the laboratory of Dr. Thomas Ried. During her time in the Ried lab, she utilized RNA interference screening techniques followed by microarray analysis to elucidate genes that regulate the viability of colorectal cancer cells.
In 2009, she began her independent career as the Walther Cancer Assistant Professor in the Department of Chemistry and Biochemistry at the University of Notre Dame and was promoted to the Charles L. Huisking Associate Professor in 2015. She has been recognized with a NSF CAREER award (2014), a Society for Analytical Chemists of Pittsburgh Starter Grant Award (2011), and a Rising Star Award from the American Chemical Society (2016). Amanda moved her research program to the Department of Chemistry and Biochemistry at The Ohio State University in January 2018 and was awarded the Presidential Early Career Award for Scientists and Engineers (PECASE) in 2019. In 2020, she was awarded a Fulbright Scholar Award and will spend a semester as a Visiting Professor at the Maastricht MultiModal Molecular Imaging Institute at Maastricht University in the Netherlands.
Emily Sekera, PhD
The Ohio State University
Emily Sekera earned her B.S. in chemistry at Rochester Institute of Technology in 2015. She then completed her graduate studies in analytical chemistry at University at Buffalo, in the laboratory of Prof. Troy D. Wood studying disease states using -omics based techniques and high resolution mass spectrometry. She is currently a postdoctoral researcher working under Dr. Amanda B. Hummon investigating at the intersection of cancer biology and analytical chemistry.
Fernando (Ralph) Tobias, PhD
The Ohio State University
Fernando Tobias is currently a postdoctoral scholar in the Hummon Research Group. His current research focuses on several projects involving lipidomic, proteomic, glycomic, and MS imaging studies on the effects of chemotherapeutic in colorectal cancer. He obtained his Ph.D. degree working in the Cologna Research Group at the University of Illinois at Chicago conducting. He conducted lipidomic studies by LC-MS and MS imaging to elucidate biochemical changes in several neurodegenerative diseases.
Nicole Beller, MS
The Ohio State University
Nicole Beller received her B.S. in Biochemistry from Wayne State University in 2018. That same year she joined the Ohio State University where she earned her M.S. in Chemistry. Nicole is currently a fourth year graduate student working under the guidance of Dr. Amanda Hummon. Nicole's current research focuses on bottom-up proteomic analysis of pulse-chase SILAC labeled three-dimensional multicellular spheroids.
Yijia Wang
the Ohio State University
The Hummon lab studies colorectal cancer by mass spectrometry. In this session, they will describe on going work in the lab to examine molecular distributions in primary colon tumors and 3D cell culture models by mass spectrometry.
The Michael S. Bereman Award for Innovative Clinical Proteomics : Breakthrough or Bust? Thyroglobulin Measurement by LC-MS/MS
Christopher Shuford, PhD
Labcorp
Chris Shuford, Ph.D., is Associate Vice President and Technical Director for research and development at Laboratory Corporation of America in Burlington, North Carolina. Chris received his B.S. in Chemistry & Physics at Longwood University and obtained his Ph.D. in Bioanalytical Chemistry from North Carolina State University under the tutelage of Professor David Muddiman, where his research focused on applications of nano-flow chromatography for multiplexed peptide quantification using protein cleavage coupled with isotope dilution mass spectrometry (PC-IDMS). In 2012, Chris joined LabCorp’s research and development team where his efforts have focused on development of high-flow chromatographic methods (>1 mL/min) for multiplexed and single protein assays for clinical diagnostics.
The Michael S. Bereman Award for Innovative Clinical Proteomics recognizes recent innovations in clinical proteomics from early- and mid-career scientists. The awardee is honored at the annual meeting of MSACL, where they will be invited to give a lecture. Nominees will be reviewed annually by a rolling award committee.
The 2021 Awardee of the Michael S. Bereman Award for Innovative Clinical Proteomics is Christopher Shuford, Ph.D. for groundbreaking work on calibration and sensitivity.
Dr. Shuford will accept this award with a presentation : Breakthrough or Bust? Thyroglobulin Measurement by LC-MS/MS.
Proteolysis-aided workflows can effectively eliminate autoantibody complexes and allow for interference-free protein quantification by mass spectrometry with surrogate peptides. Owing to the prevalence of autoantibodies in thyroid cancer patients and associated interference among immunoassay platforms, the purported poster child for mass spectrometry-based protein measurements has been Thyroglobulin (Tg). However, many other factors contribute to the utility of measurement procedures for tumor makers such as Tg, including throughput, ruggedness, trueness, and sensitivity. This presentation will focus on these limitations
Vitamin D metabolites and the gut microbiome in older men
Robert Thomas, MD PhD
University of California, San Diego
I grew up in San Diego, CA and Arlington, VA. I attended Santa Clara University where I received a B.S. in chemistry. I joined the MD PhD program at UCSD in 2007 and completed a PhD in Biomedical Sciences with a specialization in Anthropogeny. I continued at UCSD for residency training in internal medicine and completed a year as chief resident in 2019-2020. In June of 2020, I started my Endocrinology Fellowship. I plan to pursue a career in academic medicine that combines clinical endocrinology with outcomes research in Vitamin D metabolism.
Using the MrOS database and mass spectrometry, we demonstrate that 1,25(OH)2 Vitamin D, 24,25(OH)2 Vitamin D, and their associated metabolite ratios are associated with gut microbial diversity in older community dwelling men. Notably, 25(OH) Vitamin D levels did not show this association. We also demonstrate that firmicutes which frequently produce butyrate are associated with higher levels of activated Vitamin D. Overall, the project demonstrates that quantifying Vitamin D metabolites may provide more clinically relevant measures of Vitamin D metabolism.
Dr. Stefani Thomas is an Assistant Professor in the Department of Laboratory Medicine and Pathology at the University of Minnesota, and the Associate Medical Director of the M Health Fairview University of Minnesota Medical Center West Bank Laboratory. She earned a BA in Biological Sciences from Dartmouth College, a PhD in Pharmaceutical Sciences from the University of Southern California, and she completed a Clinical Chemistry postdoctoral fellowship at Johns Hopkins. Her research program at the University of Minnesota utilizes mass spectrometry-based clinical proteomics for therapeutic and diagnostic biomarker development.
Carly Twigg, BS
University of Minnesota
I am a researcher in the Thomas lab working on identifying PARP inhibitor-induced autophagosome-associated proteins to determine the means of resistance during PARPi treatment in high-grade serous ovarian cancers.
Jesenia Perez, B.S
University of Minnesota
I am a PhD student in the Microbiology, Immunology, and Cancer Biology (MICaB) program at the University of Minnesota. The goal of my research is to study the molecular mechanisms of PARP inhibition in HGSOCs containing BRCA1/2 mutations and comparing these responses to wild-type BRCA1/2 ovarian cancers. By studying the differential responses that HGSOCs have on PARP inhibition at the level of the proteome, we can ascertain which type of HGSOCs would benefit most with PARP inhibition with minimal risk of relapse. Finally, studying changes in the proteome upon PARP inhibition will reveal other sets of genes besides BRCA1/2 that are involved in homologous recombination dysfunction.
Joohyun Ryu, PhD
University of Minnesota
I received my Ph.D. in Biology from Kongju National University in South Korea. During my Ph.D. program, I studied in the Medical Proteomic Research Center at the Korea Research Institute of Bioscience and Biotechnology (KRIBB). In Medical Proteomics Research Center, KRIBB, I performed proteome-based approaches for mining the molecular targets and susceptibility markers of various diseases such as cancers, senescence, neurodegenerative disorder, leukemia, psoriasis and rheumatism and investigated the molecular mechanisms for deeper understanding of diseases. After I received my Ph.D., I obtained as position of a Postdoctoral Researcher in the Division of Molecular and Cellular Biology at the Hormel Institute, University of Minnesota. At the Hormel Institute, I was a proteomics and mass spectrometry specialist, and I have worked on studying the analysis of protein modification and proteome quantification for drug discovery and molecular targeting in a variety of cancers for medical research as well as on structural analysis of protein complexes with cross-linking mass spectrometry. In addition, I have studied the epigenetic modifications to understand the regulatory mechanism of epigenetic marks in the chromatin and cancer biology fields. Currently, I am a Researcher 5 in Dr. Stefani Thomas Lab at University of Minnesota. My research is focused on ovarian cancer biology using discovery and targeted mass spectrometry-based proteomics.
Jolene Duda, BS
University of Minnesota
I am a graduate student at the University of Minnesota in the department of Biochemistry, Molecular Biology, and Biophysics under the mentorship of Dr. Stefani Thomas. My initial project is focused on a mass-spectrometry based approach to evaluate the utility of HDAC and PARP inhibitors in ovarian cancer treatment with an emphasis on determining how epigenetic modifications confer treatment sensitivity in the context of homologous recombination proficiency or deficiency. Overall, I believe my current research plan will support the development of biomedical breakthroughs improving treatment opportunities for patients with this lethal gynecological malignancy.
Lab Showcase meetings are opportunities for lab PIs and Directors to share their scientific goals and ambitions, and introduce the labs' current projects and scientists to our community.
The Thomas lab applies discovery and targeted mass spectrometry-based proteomics methods to elucidate the biology of ovarian cancer. The common theme among the current research projects in the lab is the determination of protein-based signatures of sensitivity to ovarian cancer treatment. We are excited to share summaries of the following research projects during the Lab Showcase: "Proteome-level determinants of response to PARP inhibitor treatment in ovarian cancer," "HDAC inhibitor sensitization of high-grade serous ovarian cancer cells to PARP inhibitor treatment," "Development and validation of targeted mass spectrometry assays to detect ovarian cancer protein biomarkers," and "Longitudinal proteome alterations in high-grade serous ovarian cancer patient-derived xenografts."
Center of Membrane Biochemistry and Lipid Research
University Hospital and Faculty of Medicine Carl Gustav Carus of TU Dresden
Maria Fedorova studied Biochemistry at Saint-Petersburg State University, Russia and obtained her PhD at Faculty of Chemistry and Mineralogy, Leipzig University, Germany. She worked as a group leader at the Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, at the University of Leipzig. In August 2021 Maria group moved to the Center for Membrane Biochemistry and Lipid Research, University Hospital and Faculty of Medicine Carl Gustav Carus at TU Dresden.
Her research is focused on development and implementation of lipidomics and bioinformatics solutions to address complexity and plasticity of lipid metabolism in variety of biological systems. In particular, Maria aims for a deeper understanding of pathophysiology of metabolic and inflammatory disorders, including obesity, insulin resistance, type II diabetes and cardiovascular disorders. Another focus of Maria’s research is the development and application of mass spectrometry-based methods for the analysis of the epilipidome, which is a subset of the lipidome formed by lipid modifications aiming to increase the regulatory capacity of biological systems. Her group examines the role of modified lipids specifically in signalling processes, regulating physiological and pathological events at the cellular and organismal levels.
Michele Wölk, PhD
Center of Membrane Biochemistry and Lipid Research University Hospital and Faculty of Medicine Carl Gustav Carus of TU Dresden
During her PhD at the University of Leipzig, Michele characterized alterations in milk proteome and lipidome upon processing and seasonal changes by mass spectrometry. Now she is starting her PostDoc in Fedorova group. Using various analytical techniques including mass spectrometry, she wants to understand the role of lipid metabolisms in ferroptotic cell death.
Palina Nepachalovich, Diploma in Chemistry
Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, University of Leipzig, Germany
I started my research career as a chemist in the lab of Prof Oleg Shadyro at the Belarusian State University in Minsk, where I have been working on investigating new routes of free-radical degradation of biomolecules, paying special attention to lipids. Being now a Master's student in the Dr Maria Fedorova group, I pursue my path in lipid research and focus on the in-depth characterization of the lipid peroxidation process in obesity and in vivo models of ferroptosis by means of LC-MS/MS-based lipidomics and epilipidomics.
Zhixu Ni, PhD
Center of Membrane Biochemistry and Lipid Research, University Hospital and Faculty of Medicine Carl Gustav Carus of the Technical University Dresden
Zhixu Ni is a postdoc researcher at the Fedorova research group. Originally coming from analytical chemistry background (MSc, Leipzig University, Germany), Zhixu Ni transitioned to data analysis and software development during his PhD study on MS based lipidomics. Zhixu Ni’s main research interest is the dysregulation of enzymatically and non-enzymatically modified lipidome and metabolome in metabolic disorders with a strong focus on the high throughput LC-MS lipidomics data analysis and integration of multi-omics data. He is the main developer of several open source lipidomics tools including LipidHunter2, LPPtiger, LipidCircos, and LipidLynxX.
Lab Showcase meetings are opportunities for lab PIs and Directors to share their scientific goals and ambitions, and introduce the labs' current projects and scientists to our community.
Oleg Karaduta, MD University of Arkansas for Medical Sciences
Fireside chat with Chris Rose on Single Cell Proteomics
Christopher Rose, PhD
Genentech
Chris received his PhD in Analytical Chemistry from the University of Wisconsin Madison where he developed novel quantitative proteomics approaches in the lab of Joshua Coon. Chris continued his post-doctoral studies in the lab of Steve Gygi at Harvard Medical School where he co-developed TOMAHAQ - a targeted mass spectrometry method that combines sample and peptide multiplexing - and developed the proof-of-principle implementation of real-time search for isobaric label based quantitation. Following his post-doc, Chris joined the Microchemistry, Proteomics & Lipidomics department at Genentech where his group develops and applies leading edge quantitative proteomics methods to explore biological pathways related to potential therapeutic targets. Chris' group also focuses on analysis of low-level proteomes with a special focus on understanding technical challenges of current approaches to single cell proteomics and proposing new methods to analyze such samples.
High chemical resolution lipid imaging mass spectrometry using gas-phase ion/ion reactions
Boone Prentice, BS, PhD
University of Florida
Boone M. Prentice received his B.S. degree in Chemistry with Honors and Distinction from Longwood University (Farmville, VA) in 2008 with minors in Biology and Mathematics. At Longwood, he conducted electroanalytical research focused on developing biosensors under the supervision of Professor Melissa C. Rhoten. He attended graduate school at Purdue University (West Lafayette, IN) under the mentorship of Professor Scott A. McLuckey and received a Ph.D. in Chemistry in 2013. His Ph.D. research focused on ion trap mass spectrometry (MS) instrumentation development as well as gas-phase ion/ion and ion/molecule reactions involving biopolymers. Boone then worked as a postdoctoral research fellow in Professor Richard Caprioli’s laboratory at Vanderbilt University (Nashville, TN) where he studied matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) instrumentation and applications. Specifically, he worked on Fourier transform ion cyclotron resonance (FT-ICR) and time-of-flight (TOF) MS systems and applied IMS to the study of diabetes, cancer, drug delivery, and infectious disease. Boone joined the Department of Chemistry at the University of Florida as an Assistant Professor in the fall of 2018. His research focuses on developing next-generation bioanalytical mass spectrometry to better understand the molecular basis of health and disease.
Imaging mass spectrometry is a powerful technology that enables the visualization of biochemical processes directly in tissues by combining the molecular specificity of mass spectrometry with the spatial fidelity of microscopic imaging. Especially when studying lipids, there are many isobaric and isomeric molecules that complicate spectral analysis, with each isoform having a potentially unique cellular function. While traditional tandem mass spectrometry (MS/MS) approaches can distinguish amongst these compounds in select instances, this is often not the case. Our group is developing gas-phase reactions that afford the ability to provide improved molecular specificity without manipulating the sample. These gas-phase transformations are fast, efficient, and specific, making them ideally suited for implementation into imaging mass spectrometry workflows to enable novel structural identification and separation based on chemical reactivity. While traditional analytical analyses oftentimes simply use the mass spectrometer as a detector of molecular mass, we instead use the mass spectrometer as a reaction vessel to perform unique gas-phase transformations to provide unparalleled levels of chemical resolution.
Adam Rosebrock, PhD Stony Brook School of Medicine
Developing Advanced Protein Biomarker Tests to Address Key Unmet Clinical Needs
Stephen Pennington, PhD
University College Dublin, School of Medicine
Steve graduated from Imperial College of Science and Technology (Imperial College London) with a joint honours degree in Chemistry and Biochemistry before completing a PhD in Biochemistry at the University of Cambridge. Subsequently, he was an Elmore Medical Research Fellow in the Department of Biochemistry in Cambridge University.
His research team in University College Dublin (UCD; www.ucd.ie) is currently developing multiplexed protein biomarker measurements using multiple reaction monitoring mass spectrometry to support the translation of novel multiplexed blood protein biomarkers to clinical diagnostic tests.
Steve is currently co-leading HIPPOCRATES with a rheumatologist colleague. HIPPOCRATES is an Innovative Medicines Initiative public-private partnership; it is a 22.5Million Euro project with 27 partners and seeks to address key unmet met needs in psoriatic disease. Patients and patient representative organisations are involved in all aspects of the project.
In 2017 he was the lead organiser of the 16th Human Proteome Organisation (HUPO) World Congress, which was held in Dublin and included a Gala Dinner at which former US Vice-President Joe Biden was guest speaker.
Steve is currently Professor of Proteomics and Senior Fellow, UCD Conway Institute and past President of HUPO (www.hupo.org)
The challenges of developing new protein biomarker tests and delivering them to use for patient benefit will be presented. In the context of a recently initiated EU IMI consortium, particular emphasis will be placed on analytical validation of new multiplexed protein biomarker assays and their use in multi-centre evaluation and validation studies to support the development of new tests in psoriatic disease. Patient engagement and use of patient centric sampling devices for effective test delivery will be introduced.
Laura Owen Salford Royal NHS Foundation Trust & University of Manchester
Grace van der Gugten, B.Sc. Chemistry Alberta Precision Laboratories
Practical Training : Taking Aim at Interference (Without Shooting Yourself in the Foot)
Zlata Clark, PhD
B.S. in Analytical Chemistry, Masaryk University, Brno, Czech Republic.
Ph.D. in Bioanalytical Chemistry, Brigham Young University, Provo, Utah.
Nearly three decades of HPLC, CE, CE-MS, and LC-MSMS method development and validation experience in academic, pharmaceutical, and clinical laboratory environments.
The popularity of LC-MS/MS-based methods for clinical testing continues to rise. However, despite their superior analytical specificity, these methods may still suffer from interference affecting method accuracy and precision, and hence negatively impacting patient care.
The following topics and issues will be addressed:
Novel Proteomics Strategies to Identify Biomarkers for Dementias
Prof.Dr.Ir. Charlotte Teunissen
Amsterdam UMC
Charlotte Teunissen’s drive is to improve care of patients with neurological diseases by developing body fluid biomarkers for diagnosis, stratification, prognosis and monitoring treatment responses. Studies of her research group span the entire spectrum of biomarker development, starting with biomarker identification, often by –omics methods, followed by biomarker assay development and analytical validation, and lastly, extensive clinical validation and implementation of novel biomarkers in clinical practice.
She has extensive expertise with assay development on state of the art technologies, such as mass spectrometry and antibody-based arrays for biomarker discovery, ultrasensitive immunoassays, and in in implementation of vitro diagnostic technologies for clinical routine lab analysis. She is responsible for the large well-characterised biobank of the Amsterdam Dementia cohort, containing >5200 paired CSF and serum samples of individuals visiting the memory clinical of the Alzheimer Center Amsterdam (a.o. controls, patients with Alzheimer, Frontotemporal, Lewy Bodies).To ensure the quality of the biosamples, the group studies pre-analytical effects, which are key to implementation. Charlotte is leading several collaborative international biomarker networks, such as the Society for Neurochemistry and routine CSF analysis and the Alzheimer Association-Global Biomarker Standardization and Blood Based Biomarkers consortia. She is the coordinator of the Marie Curie MIRIADE project, aiming to train 15 novel researchers into innovative strategies to develop dementia biomarkers (10 academic centers + 10 non-academic centers), and the JPND bPRIDE project, that aims to develop targeted blood based biomarker panels for early differential diagnoses of specific dementias and is a collaborative project between 7 European and 1 Australian centers.
The development of disease-modifying therapies against neurological diseases such as Alzheimer
Coral Munday, BSc (Hons) Pharmaceutical and Forensic Analysis Pharmaron
Andrew Davison, PhD Royal Liverpool University Hospitals
Practical Training
The Use of Derivatization for Enhanced LC-MS/MS Methods
Catarina Horro Pita, PhD, BSc
A4P Consulting
Dr Catarina Horro Pita possesses a BSc in Chemistry and Environmental Chemistry and a PhD in Synthetic Organic Chemistry. After concluding her PhD, she initiated her professional career as a Synthetic Chemist, prior to moving into Analytical Chemistry and Bioanalysis. She has been working in the field of Bioanalysis for 15 years, holding both scientific and managerial positions. Catarina currently works as a PK Project Manager at A4P Consulting. During her career, she has gained significant experience in the development, validation and management of LC-MS/MS assays for the analysis of both xenobiotic compounds and small molecule biomarkers. In addition, due to her expertise in Organic Chemistry, she also has an extensive knowledge of derivatization techniques for the improvement of LC-MS/MS methods.
Derivatization is a simple chemical reaction, often used in Bioanalysis to transform a “not so ideal” candidate for LC-MS/MS analysis into a molecule with enhanced phys-chem properties, which leads to improved detectability of the compound.
The objective of this presentation is to describe some of the most commonly used derivatization procedures and explain the benefits and drawbacks of these techniques.
When performing analysis by LC-MS/MS, the ideal analyte should be chemically stable and have moderate retention on the LC column. The molecule should also be ionisable under ESI or APCI conditions and have an efficient fragmentation upon collision. In addition, the target compound should be selectively separated from other xenobiotics or endogenous products present in the extracted matrix. When the analyte does not meet all of the above criteria, derivatisation can be used to modify its chemical structure and address these issues.
A range of derivatization processes will be reviewed, indicating their bioanalytical applications and type of chemical reactions involved. In addition, examples of derivatization reagents and reaction conditions will be described.
Although the application of derivatization procedures can lead to an improved bioanalytical performance, these techniques also present a range of disadvantages, such as extended method development times, lengthy extraction procedures and increased method variability.
Despite all the recent technological improvements in the field of Bioanalysis, derivatization remains a very powerful tool to overcome problems associated with analyte instability, poor chromatographic performance, inadequate analyte ionization or unacceptable method selectivity. However, the application of derivatization procedures can often lead to an increase in assay complexity and may reduce method robustness. Therefore, both the advantages and disadvantages of these procedures should always be considered before their application to a bioanalytical method.
Untargeted Metabolomics of COVID-19 Patient Serum Reveals Potential Prognostic Markers of Both Severity and Outcome
Ivayla Roberts, MSc, MRes
University of Liverpool
Ivayla Roberts is a doctoral researcher at the University of Liverpool in Prof. Kell system biology group. Originally coming from computer science background (MSc, Montpellier France) Iva transitioned to molecular biology research via a Translational Molecular Medicine MRes (Manchester, UK).
Iva’s research interests are metabolomics, mass-spectrometry, and the application of statistical and machine learning computational approaches to metabolomics.
Iva’s PhD is focused on metabolomics in COVID-19.
The diagnosis of COVID-19 is normally based on the qualitative detection of viral nucleic acid sequences. Properties of the host response are not measured but are key in determining outcome. Although metabolic profiles are well suited to capture host state, most metabolomics studies are either underpowered, measure only a restricted subset of metabolites (‘targeted metabolomics’), compare infected individuals against uninfected control cohorts that are not suitably matched, or do not provide a compact predictive model.
We here provide a well-powered, untargeted metabolomics assessment of 120 COVID-19 patient samples acquired at hospital admission. The study aims to predict patient’s infection severity (i.e. mild or severe) and potential outcome (i.e. discharged or deceased).
High resolution untargeted LC-MS/MS analysis was performed on patient serum using both positive and negative ionization. A subset of 20 intermediary metabolites predictive of severity or outcome were selected based on univariate statistical significance and a multiple predictor Bayesian logistic regression model. The predictors were selected for their relevant biological function and include cytosine and ureidopropionic acid (reflecting viral load), kynurenine (reflecting host inflammatory response), and multiple short chain acylcarnitines (energy metabolism) among others.
Currently, this approach predicts outcome and severity with a Monte Carlo cross validated area under the ROC curve of 0.792 (SD 0.09) and 0.793 (SD 0.08), respectively. A blind validation study on additional 90 patients predicted outcome and severity at ROC_AUC of 0.83 (CI 0.74 – 0.91) and 0.76 (CI 0.67 – 0.86). Prognostic tests based on the markers discussed in this paper could allow improvement in the planning of COVID-19 patient treatment.
Thermo Fisher Scientific : Automated Mass Spectrometry in the high-throughput centralized diagnostic laboratory. Field integration experience, new routine diagnostics and research perspectives at CDI Milan, Italy
Part 1: Importance of automated LC-MS/MS in a high robotized Central Laboratory: our opinion and experience at CDI, Milan, IT Dr. Fulvio Ferrara, CDI Milan, IT
Part 2: Highway to automated mass spectrometry: from traditional LC-MS/MS to high troughput diagnostic solution Prof. Gardana, Milan University, IT
Part 3: New method development in Mass Spec and expansion in Dx routine Dr Giacomo Visconti, CDI Milan, IT
Part 4: MS Spectrometry and genetics/epigenetics synergic perspective: a new challenge to discover the passage to the
Flaminia Fanelli, PhD Dept. of Medical and Surgical Science, University of Bologna
Challenges and opportunities for an extended steroid profiling (steroidomics) in biological fluids
Serge Rudaz, PhD
School of Pharmaceutical Sciences
University of Geneva – Switzerland
Serge Rudaz is Associate Professor at the University of Geneva where he leads the biomedical and metabolomics analysis (BMA) group. He's President of the Swiss Metabolomics Society (SMS), vice-president of the Competence Center in Chemical and Toxicological Analysis (ccCTA) and member of the management Board of the Swiss Centre for Applied Human Toxicology (SCAHT) Foundation. Serge Rudaz contributed to the field of analytical sciences with diverse activities, including invited lectures and invited/visiting professorships at various Universities; Lyon (France), Pavia (Italy), Guanzhou (China).
He is interested in steroids analysis, metabolomics, (UHP)LC and CE coupled to MS, advances in sample preparation, analysis of pharmaceuticals and counterfeits medicines, biological matrices, clinical and preclinical studies, including metabolism and toxicological analysis. He is a (co)author of over 10 book chapters and more than 320 peer-reviewed papers, with an H-index (Scopus) of 57. He was chair/co-chair of several national or international congress, such as Chimiométrie 2015, SEP 2017 and MSB 2020.
Historical compounds of interest are pharmaceutical substances, chiral products, and exogenous analytes. For several years, a major focus has been placed on the implementation of various strategy allowing the investigation of endogenous metabolites, including an extended steroid profiles (i.e.
Laura Owen Salford Royal NHS Foundation Trust & University of Manchester
Coral Munday, BSc (Hons) Pharmaceutical and Forensic Analysis Pharmaron
Practical Training
Getting Started with New MS Systems
Jo Adaway, BSc, MSc, PhD
Manchester University NHS Foundation Trust
Jo Adaway is a Consultant Clinical Scientist at Manchester University NHS Foundation Trust. She is interested in developing LC-MS/MS assays for small molecules for endocrinology and neuroendocrine tumour applications and has recently branched out into protein quantification. She was awarded her PhD on Proteomic analysis of stem cell commitment in 2005 from the University of Manchester. She is Associate Editor for Annals of Clinical Biochemistry and honorary senior lecturer at the University of Manchester, where she lectures on chromatography, mass spectrometry and endocrinology.
You’ve successfully purchased a mass spectrometer for your clinical lab – what on earth do you do now? In this session, we will discuss the practicalities of what to do next, from training your staff and developing your first method, to integrating the technology into your lab. We will focus on basics that are really important to successfully running a mass spec service but which may not be included in other training programmes, including how to choose solvents, useful peripheral equipment and sources of information and support.
Interconversion: When Your Prince Charming Turns into a Frog… Can You Turn Him Back?
Stephanie Keane, BSc (Hons) Forensic Science
LGC
Steph graduated from the University of Lincoln, UK with a BSc (Hons) Forensic Science. She has worked at the LGC Fordham site since 2013 and is working as a Senior Scientist, in a Technical Specialist role. Her role includes method development of LC-MS/MS methods, training and mentoring others through method development, and instrument troubleshooting/maintenance. Steph is also a member of the Chromatographic Society. Outside of work Steph’s main passions are guinea-pigs and mountain biking.
When analysing patient samples the concentration of the analyte measured should mirror the concentration during sample collection; therefore consideration should be given to the pre analytical conditions of the samples. One such consideration in multi-analyte studies is the potential for interconversion between analytes, which can compromise this quantification, leading to potential overestimation of one analyte and underestimation of another. In this session the root causes of interconversion shall be discussed, from the reversible hydrolysis of lactones e.g. statin drugs to cleavage of ester bonds by esterases. We will be examining the entire life-cycle of a patient sample to allow identification of problem areas in a methodology. We shall examine how to create a robust and accurate method with particular focus on stabilisation protocols and practicalities for the clinical laboratory. How to calculate levels of interconversion shall be demonstrated and the ability to assess impact upon data discussed.
Shimadzu : Blood test for neurodegenerative diseases : Are we ready? Implementation of high-performance amyloid-beta quantification diagnostic on the Clinical Proteomics Platform of Montpellier Hospital (France)
Oleg Mayboroda, PhD Leiden University Medical Center
Harnessing the Exposome, Cheminformatics and Mass Spectrometry for Clinical Metabolomics
Emma Schymanski, Dr. rer. nat.
LCSB, University of Luxembourg
Associate Professor Emma Schymanski is head of the Environmental Cheminformatics (ECI) group at the Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg. In 2018 she received a Luxembourg National Research Fund (FNR) ATTRACT Fellowship to establish her group in Luxembourg, following a 6 year postdoc at Eawag, the Swiss Federal Institute of Aquatic Science and Technology and a PhD at the Helmholtz Centre for Environmental Research (UFZ) in Leipzig, Germany. Before undertaking her PhD, she worked as a consulting environmental engineer in Perth, Australia. She has over 80 publications and a book, and is involved in many collaborative software efforts. Her research combines cheminformatics and computational (high resolution) mass spectrometry approaches to elucidate the unknowns in complex samples, primarily with non-target screening, and relating these to environmental causes of disease. An advocate for open science, she is involved in and organizes several European and worldwide activities to improve the exchange of data, information and ideas between scientists to push progress in this field, including NORMAN Network activities (e.g. NORMAN-SLE https://www.norman-network.com/nds/SLE/), MassBank (https://massbank.eu/MassBank/), MetFrag (https://msbi.ipb-halle.de/MetFrag/) and PubChemLite for Exposomics (https://doi.org/10.5281/zenodo.4432123).
The multitude of chemicals to which we are exposed is ever increasing, with over 110 million chemicals in the largest open chemical databases, over 350,000 in global use inventories, and over 70,000 estimated to be in household use alone. Detectable molecules in exposomics can be captured using non-target high resolution mass spectrometry (HRMS), which provides a
The Study of Metastasis into Signaling Lymph Nodes Upon Breast Cancer: From Molecular Mechanisms to Express Diagnostics
Vladimir Frankevich, PhD
FSBI «National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I.Kulakov» Ministry of Healthcare of the Russian Federation
Introduction.
Breast cancer is a very serious problem worldwide. Breast cancer is accompanied by the metastatic lesion of the lymph nodes in 40-50% of cases. Currently, histology analysis is used during the surgery in order to verify the occurrence of metastasis in lymph nodes. Faster and more specific methods are urgently required for the identification of metastatic lesion in lymph nodes directly during the surgery.
Methods.
We present the new method based on the internal extractive electrospray ionization (iEESI) combined with high-resolution mass spectrometry analysis. It allows us to perform rapid (less than 5 minutes) molecular profiling of breast tissue and signal lymph nodes tissue with regard to presence of metastatic lesion. The distinctive feature of proposed ionization method allows the direct extraction of whole-volume biopsy tissue samples rather than just their surface. It makes it possible to substantially increase the sensitivity, accuracy and reproducibility of analysis compared with existing analogues. New analytical advancements were implemented which allow the sequential ionization of lipids, metabolites and proteins from the same single biopsy tissue sample.
Results.
Rapid diagnosis of the metastatic lesion of the signal lymph nodes upon invasive breast cancer on the biopsy tissue samples was performed in 50 patients. The signals of differential metabolites associated with the occurrence of lymphatic lesion were identified using high-resolution tandem MS analysis and reference LC-MS analysis. Bioinformatics approaches were developed in order to study the complex relationships between the identified metabolites. This led us to create of a molecular model of metastasis process.
Conclusions.
A minimally invasive method has been developed for the diagnosis of metastatic lesions of signal lymph nodes in invasive breast cancer based on direct mass spectrometric analysis. A mechanism for metastasis to the signal lymph nodes in breast cancer was proposed.
Novel Aspect.
A new method for mass spectrometric analysis of biopsy samples based on internal extractive electrospray ionization has been developed.
Acknowledgments.
The work was supported by Russian Foundation for Basic Research (Agreement ? 19-515-5502119).
Laura Owen Salford Royal NHS Foundation Trust & University of Manchester
Jo Adaway, BSc, MSc, PhD Manchester University NHS Foundation Trust
Practical Training
Translation of Urinary Steroid Metabolomics from a Research Test into Routine Clinical Biochemistry
Angela Taylor, PhD
University of Birmingham
Angela is interested in the development of highly sensitivity, high throughput, well validated mass spectrometry assays for steroid analysis. Application of these assays to answer important clinical questions is critical to her research. She feels the truly translational aspect of the work conducted at the Steroid Metabolome Analysis Core (SMAC) means the work is both analytically enjoyable and socially beneficial.
Angela has an analytical chemistry master’s degree from Swansea University (2005). In 2009 she received her PhD from Swansea University investigating steroid metabolism in the human endometrium using mass spectrometry. This was followed by post-doctoral work at the University of Birmingham working for Prof Wiebke Arlt, which cumulated in setting up the SMAC facility in 2016. The SMAC lab now conducts steroid research from wet lab based projects to clinical trials.
Translation of a test from the initial hypothesis to routine clinical use is a long and challenging journey. In this session I will discuss my experiences in the research laboratory focusing on the development of ‘urinary steroids metabolomics’ a combination of mass spectrometry and machine learning for diagnosis of adrenocortical carcinoma (ACC).
The journey starts with the hypothesis developed by Wiebke Arlt and Cedric Shackleton that urinary steroid excretion in patients with adrenal cancers would differ from those with benign adrenal adenomas (ACA). Initial studies were undertaken investigating 32 steroid metabolites using gas chromatography mass spectrometry (GC-MS). Through collaboration with computer scientists Michael Biehl and statisticians Alice Sitch and John Deeks, we were able to identify a malignant steroid fingerprint that differentiated ACC from ACA. When compared to current available imaging technologies, this urine steroid metabolomic assay demonstrated improved diagnostic sensitivity and specificity.
GC-MS is technically challenging and time consuming making it an expensive assay unsuitable for routine clinical use. Therefore, we selected the most relevant steroids when distinguishing between ACC and ACA and developed and validated a liquid chromatography tandem mass spectrometry (LC-MS/MS) assay for a subset of 15 steroids. Firstly, this was cross-validated to GC-MS to compare quantitation and diagnostic performance. Secondly, we prospectively validated the assay in a cohort of approximately 2000 unbiasedly recruited patients with adrenal tumours. Finally, we were able to determine the optimal stage in the patient pathway to place our assay to aid the diagnosis of ACC.
We are currently working towards the implementation of this assay into routine clinical biochemistry. It has taken us 10 years from the initial concept to its implementation, only possible through the work of a multi-disciplinary team. There have been many challenges on this pathway, I will discuss how we overcame these in this session.
Urine steroid metabolomics as a biomarker tool for detecting malignancy in adrenal tumors. Arlt W, et al. J Clin Endocrinol Metab. 2011 96(12):3775-84.
Urine steroid metabolomics for the differential diagnosis of adrenal incidentalomas in the EURINE-ACT study: a prospective test validation study. Bancos I Taylor AE, et al. Lancet Diabetes Endocrinol. 2020 8(9):773-781.
Peptide Analysis by LC-MS/MS
Gwen Wark, BSc, PhD, MSc, FRCPath
Berkshire and Surrey Pathology Services
Gwen Wark is a consultant clinical biochemist employed within the Blood Sciences department of Berkshire and Surrey Pathology Services. She has worked at the Royal Surrey County Hospital in Guildford for over 22 years where she is now Director of the Supraregional Assay Service (SAS) Peptide Hormones Laboratory which specialises in the investigation of hypoglycaemia (includes a forensic case load) and the role of insulin-like growth factors and their binding proteins. Since 2002, she has also been the Scheme Director of the UK National External Quality Assessment Service (UK NEQAS) Guildford Peptide Hormones Scheme which covers the analytes insulin, C-peptide, gastrin, insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3). Since 2019, she has also been Director of the UK NEQAS Trace Elements schemes. She is involved in developing accuracy-based proficiency testing for all scheme analytes.
Gwen is also involved in promoting the development of reference methods/measurement systems. She is a member of the British Standards Institution (BSI) CH/212 committee which is responsible for standardisation in the field of in vitro diagnostics and reviewing/developing ISO standards. She is a member of the IFCC working group (collaboration with ADA and EASD) for the standardisation of insulin assays and a guest member of the NIDDK led C-peptide standardisation committee. In collaboration with the National Institute for Biological Standards and Control (NIBSC), she has been involved in the development of the WHO International Standards for IGF-I, insulin, C-peptide and proinsulin. She collaborated in the workshop that culminated in the ‘Consensus Statement on the Standardisation and Evaluation of Growth Hormone and Insulin-like Growth Factor Assays’ and also development of mass spectrometric assays for the measurement of IGF-I. Current LC-MS/MS assay development is focussed on developing further LC-MS/MS peptide assays for implementation into the routine laboratory e.g. insulin and C-peptide.
In the routine laboratory, the use of LC-MS/MS is becoming more widespread and is often used to overcome issues encountered with immunoassays. In this presentation, issues with peptide hormone analyses by LC-MS/MS and consensus statement recommendations will be discussed. Insulin and IGF-I will be used to highlight analytical approaches that be adopted to enable implementation of LC-MS/MS into the routine laboratory.
Anna Nicolaou, BSc PhD CChem FRSC The University of Manchester
Erika Dorado, MSc, PhD Imperial College London
Bringing Clinical Mass Spectrometry to Patient Care - 20 Years of Experience from Research to Clinical Application
Uta Ceglarek, PhD, Prof. Dr. rer. nat.
Leipzig University
Dr. Uta Ceglarek, PhD, EuSpLM is senior scientist at the University Hospital Leipzig, Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics (ILM). She is board certified in Clinical Chemistry and Laboratory medicine (EuSpLM), in Toxicology and passed her postdoctoral lecture qualification in Clinical Chemistry and Laboratory Medicine.
Her research efforts are focused on the development of new mass spectrometric concepts for metabolome and proteome analysis in human body fluids and the investigations of metabolic alterations and lipid-modification in dyslipidemia, metabolic syndrome and cardiovascular diseases.
Over the past two decades clinical mass spectrometry becomes increasingly importance as analytical tool in routine diagnostics. LC-MS/MS offers a rapid, effective and economical way to analyze metabolic alterations of pre-defined target metabolites in biological samples. Recent developments open the way to implement quantification of proteins into clinical routine, too. Until now, access to clinical applications of LC-MS/MS have been restricted to specialist centers. The increasing availability of commercial assays, certified instruments, and a growing number of commercial solutions for mass spec lab automation will help to overcome this limitation.
However, for implementation into 24/7 patient care special requirements to laboratory diagnostic approaches have to be addressed. This presentation will give an overview to the current status aof LC-MS/MS applications like newborn screening, therapeutic drug monitoring, steroid analysis and quantitative protein analysis. Experiences from more than 20 years of implementation and maintenance of LC-MS/MS in our 24/7 diagnostic laboratory will be discussed. Perspectives for future developments in laboratory medicine directing to the clinical aim of predictive, preventive and personalized medicine by metabolomic and proteomic approaches will be depicted.
Lucia Grenga is a researcher in the laboratory of Innovative Technologies for Detection and Diagnostics at the French Alternative Energies and Atomic Energy Commission (CEA). She is interested in the development of tandem mass spectrometry‐based methodologies and their integration with other omics approaches for the characterization of clinically relevant microbiomes.
Proteomics offers a wide collection of methodologies to study biological systems at the finest granularity. Faced with COVID-19, the most worrying pandemic in a century, a collective mass spectrometry effort was launched to study COVID-19 and propose alternative solutions for the detection of SARS-CoV-2. Since then, proteomics researchers have made significant progress in understanding how its causative virus SARS-CoV-2 hijacks the host's cellular machinery and multiplies exponentially, how the disease can be diagnosed, and how it develops, as well as its severity predicted. Numerous cellular targets of potential interest for the development of new antiviral drugs have been documented. The main findings gathered by our group and other proteomists will be discussed while pointing out how they could represent game-changers in the COVID-19 battlefield and in deciphering the long-term consequences of the infection.
Alcohol Biomarkers : Which ones (not) to use, and in what context?
Liesl Heughebaert, Master in Pharmaceutical Care
Ghent University
After successfully completing my Master in Pharmaceutical Care, I graduated as pharmacist in 2020. Mainly due to the interesting research performed during my Master’s thesis in the laboratory of Toxicology of prof. Christophe Stove, I decided to further pursue a career in science and research and started my PhD a few months after graduating. Currently, my work is mainly focusing on automation of microsampling-based analysis, including hematocrit prediction of dried blood microsamples (conventional dried blood spots and samples collected via volumetric absorptive microsampling) and the development of automated microsampling-based LC-MS/MS methods for the analysis of vitamins. Apart from research, I have also been involved in the organization of the last two Young Scientist Symposia of the European Bioanalysis Forum (EBF). I am (co-)author of 6 peer-reviewed publications.
Katleen Van Uytfanghe, Dr.
Laboratory of Toxicology, Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium
I graduated in 2001 as a Master of Sciences in Chemistry at Ghent University. From 2001 to 2007 I did my PhD in the Laboratory of Analytical Chemistry at the Faculty of Pharmaceutical Sciences at Ghent University, followed by a post-doc in the same laboratory. Since October 2014 I'm a postdoctoral fellow at the Laboratory of Toxicology at Ghent University, where I am the quality manager and technical supervisor of the ISO17025 and ISO15195 accredited reference laboratory (Ref4U) section and the forensic service section of the lab. Besides this, I am the scientific secretary of the International Federation of Clinical Chemistry and Laboratory Medicine Committee for Standardization of Thyroid Function Tests.
I have expertise in development and validation of targeted GC or LC/MS (higher order reference) measurement procedures and their applications, with profound experience with method comparisons. Within the reference laboratory, the focus of the research activities is standardization and harmonization of thyroid function tests. Within the forensic applications, the focus is on determination of alcohol markers and new psychoactive substances. In 2020, I also participated in the development of a Sars-COV-2 LC/MS method.
Several biomarkers for alcohol (ab)use have been used throughout the years, including direct and indirect biomarkers. As indirect biomarkers show a low specificity and sensitivity for the detection of alcohol abuse, attention has shifted towards direct biomarkers such as ethanol itself and products derived thereof (ethyl glucuronide, ethyl sulfphate, etc.). Within the group of direct biomarkers, phosphatidylethanol (PEth) has been valued more and more since it increases the sensitivity of uncovering alcohol consumption and monitoring abstinence. With a half-life of 7-8 days, PEth provides a long detection window meaning it can take weeks for positive PEth values to drop below the decision limit for monitoring abstinence (20 ng/mL). Consequently, the question arises whether abstinence can be confirmed based on two consecutive PEth positive results.
In the first part of this session a detailed overview will be given of the abovementioned alcohol biomarkers. In the second part, the results of a large-scale PEth monitoring study will be discussed.
Methods
A large scale PEth monitoring study was set up in which over 500 participants agreed to stay sober for one month. During this period, they took 3 finger prick samples via self-sampling at home using volumetric absorptive micro sampling devices (VAMS, Mitra
Microsampling in Therapeutic Drug Monitoring and Toxicology: Where are we heading?
Christophe Stove, PhD
University of Ghent
Christophe Stove graduated in 1999 as a Pharmacist at Ghent University. From 1999 to 2003 he did his PhD in the Laboratory of Experimental Cancerology in the Faculty of Medicine at Ghent University, followed by a post-doc in the Department for Molecular Biomedical Research in the Faculty of Sciences at Ghent University-VIB and -from Oct 2007 on- a Doctor-Assistant position in the Laboratory of Toxicology.
In February 2013 he became tenure-track assistant professor in the Faculty of Pharmaceutical Sciences and since October 2014 he is in charge of the Laboratory of Toxicology.
His activities include education, service (forensic toxicology and reference measurement services) and research. Research fields of special interest are alternative sampling strategies, the deployment of bio-analytical strategies for steering vitamin research and various aspects of G-protein-coupled receptors (GPCR’s).
Ólöf Gerður Ísberg, MSc, PhD Vanderbilt University, MSACL Early Career Network
Dr Tiffany Porta, PhD (T.) Boehringer Ingelheim
Mass Spectrometry Imaging and its Role in Transforming Digital Pathology Beyond Morphological to Molecular Mapping of Tissues
Richard Goodwin, PhD
AstraZeneca, The University of Glasgow
Dr Richard Goodwin started research with MS imaging as postdoc in 2006 before moving to Uppsala University to work as an AstraZeneca post doc for Prof. Per Andrén. Richard now leads a global team of passionate imaging scientists that deliver expertise across AstraZeneca cutting-edge multidimensional imaging modalities. Deriving project insight and impact by connecting safety and efficacy endpoints using advanced tissue histology, molecular imaging, in vivo PET, MRI and much more. All connected by an integrated image analysis, digitization and AI. Passionate about collaboration and embedding new technologies and data analysis into the drug discovery process. Published over 75 publications while at AstraZeneca on the development and deployment of new technology in support of the portfolio. Honorary Professor at University of Glasgow.
Drug discovery and development constantly asks scientists to unlock more from every patient biopsy or preclinical study. Questions around drug biodistribution and metabolism merge with studies examining efficacy and safety. Therefore, researchers as AstraZeneca are collaborating extensively with researchers do develop, deploy and integrate new imaging technologies that provide a holistic view of the hidden molecular landscape in tissues. This provides data volumes and complexity ripe for AI exploration. The presentation will cover the opportunities and challenges in utilizing molecular imaging endpoints to better understand complex disease and investigate therapeutic efficacy across the portfolio of a large pharmaceutical organization.
Jörg Hanrieder, PhD Sahlgrenska Hospital - University of Gothenburg
Ólöf Gerður Ísberg, MSc, PhD Vanderbilt University, MSACL Early Career Network
Robot-assisted Spidermass for in vivo Real-time Topographical Molecular Imaging
Nina Ogrinc, PhD
Laboratoire PRISM, Université De Lille
Nina Ogrinc finished her PhD at the University of Ljubljana, and the Department of Low and Medium energy Physics, at Jozef Stefan Institute, Slovenia.
In 2014, she joined the group of Prof. Ron Heeren (M4I) in Maastricht, Netherlands as a postdoctoral researcher. During this time, she was involved in the Marie Curie BRAINPATH consortium and actively engaged in a variety of projects developing and applying new mass spectrometry imaging tools for biomarker discovery (lipids, metabolites, peptides) in neurodegenerative diseases
Since October 2018 she is working at laboratory PRISM (Inserm U1192, University of Lille), under the direction of Prof Michel Salzet and Prof. Isabelle Fournier, on a highly innovative SpiderMass project, an instrument designed for guided surgery and real-time diagnosis in the surgical operating room. She is currently developing a multimodal platform for mass spectrometry and imaging techniques which will enable complex, low cost, rapid, molecular profiling for faster cancer diagnostics and biomarker discovery.
Introduction
Surgery of solid tumors is a difficult process and the quality of surgery is central for patient outcome. Despite important improvements in surgical practices, the completeness of tumor removal remains scarce and surgeons are still struggling in the decision making. The gold standard currently remains the collection of biopsies and examination by expert pathologist. This process is long and laborious while showing an important rate of wrong assessment. We recently introduced SpiderMass technology based on water-assisted laser desorption-ionization (WALDI) which enables to retrieve the necessary molecular information directly in-vivo and in real-time. Yet, the device was demonstrated for manual profiling of tissues. However, for intraoperative diagnostics and excision margins evaluation, the device must be integrated onto a robotic device to provide precise imaging of the defined area within the body.
Methods
The SpiderMass system is composed of a remote laser microprobe, a transfer line and the MS instrument. The laser microprobe is fibered and equipped with a handpiece and tuned to 2.94
Dr. Michael Vogeser, MD, is specialist in Laboratory Medicine and senior physician at the Hospital of the University of the Ludwig-Maximilians-University Munich, Germany (LMU; Institute of Laboratory Medicine). As an Associate Professor he is teaching Clinical Chemistry and Laboratory Medicine. The main scope of his scientific work is the application of mass spectrometric technologies in routine clinical laboratory testing as translational diagnostics. Besides method development in therapeutic drug monitoring and endocrinology a further particular field of his work is quality and risk management in mass spectrometry and in clinical testing in general. Michael has published >240 articles in peer reviewed medical journals. Michael heads the Commission for In Vitro Diagnostics in the German Association of Scientific Medical Societies (AWMF).)
In vitro diagnostics in the European Union (EU) is facing fundamental change with the implementation of Regulation (EU) 2017/746 on in vitro diagnostic medical devices, known as IVDR. With its full entry into force from May 2022, the IVDR will affect a population of 447 million people in 27 countries. The regulation addresses - beyond commercially distributed products - devices manufactured in healthcare facilities. In many ways, it is not yet clear how the IVDR will actually impact in-house MS-based measurement procedures. This presentation will discuss recent documents and guidance and provide an update on the implementation process - which is the responsibility of member states. An IVDR-compliance checklist will also be presented.
Guinevere Lageveen-Kammeijer, PhD University of Groningen
Tamas Pongracz, PhD Leiden University Medical Center
Clinical Implementation of Glycan Mass Spectrometry for Genetic Glycosylation Disorders
Dirk Lefeber, PhD
Radboudumc
Dirk Lefeber, Ph.D., is Professor at the Radboud University Medical Center, Translational Metabolic Laboratory, Department of Neurology. After a PhD in chemical and analytical glycosciences at Utrecht University, followed by a post-doctoral training in polysaccharide infectiology at Utrecht UMC, he took a position as staff member Glycosylation Disorders at the Radboud UMC to establish an independent research group. He completed a training to Laboratory specialist clinical genetics in 2008, founded the Radboudumc Expertise Center for Disorders of Glycosylation, formally recognized by the Dutch government, and received several awards, including the SSIEM award (2010&2016) and prestigious personal VIDI and VICI grants from the Netherlands Scientific Organisation. He has established the world-wide quality control scheme for CDG diagnostics within ERNDIM.
Congenital Disorders of Glycosylation (CDG) form a fast growing group of genetic defects, that are characterized by abnormal glycosylation of proteins and lipids. With already more than 140 different genetic diseases discovered in all glycosylation pathways, the need for better biomarkers is increasing. This includes diagnostic biomarkers with increased specificity and sensitivity, as well as biomarkers that can predict disease progression and therapy response.
This presentation will mainly focus on CDGs due to defects in protein N-glycosylation. Screening for defects in protein N-glycosylation is occurring broadly via analysis of plasma transferrin by isofocusing, HPLC or capillary electrophoresis. Increased specificity and sensitivity is obtained by high-resolution QTOF mass spectrometry of intact plasma transferrin, which allows for screening and CDG subtyping in a single diagnostic test. For example, diagnostic glycan profiles are obtained for intellectual disability due to MAN1B1-CDG and exercise intolerance due to PGM1-CDG.
More sophisticated glycomics and glycoproteomics techniques are being applied and developed for CDG gene discovery, by stratification of patient groups. Moreover, these technologies are applied to diagnose CDG defects that don
Ilaria is currently a postdoc scientist at Imperial College London. Her main research interest is the discovery and validation of volatile biomarkers in human breath using mass spectrometry, for the development of non-invasive diagnostic techniques for early cancer detection. She obtained her PhD in analytical chemistry, working between Italy and France as part of a European PhD program.
Elizabeth Baranowski, MD
NHS
Liz is a senior clinical trainee in Paediatric Endocrinology at Birmingham Children’s Hospital and an MRC clinical research training fellow working with Professor Wiebke Arlt at the Institute of Metabolism and Systems Research, University of Birmingham, UK. She is interested in translational interdisciplinary research; combining medical, biostatistics, mass spectrometry and machine learning domains for the eventual direct benefit of patients. Her research to date focuses on non-invasive testing for patients with inherited disorders of adrenal steroid biosynthesis.
Guinevere Lageveen-Kammeijer, PhD
University of Groningen
Guinevere received her PhD on exploring prostate-specific antigen (PSA), the well-known biomarker for prostate cancer, and its glycosylation by capillary electrophoresis and mass spectrometry. Since 2022, Guinevere is appointed as an Assistant Professor (tenure track) in the Analytical Biochemistry group at the Univeristy of Groningen She currently works on further expanding a mass spectrometry-based PSA glycosylation assay which she developed during her PhD. In addition, she explores the possibilities for the in-depth analysis of glycans and intact glycoproteins for biomarker discovery for other diseases as well as for the characterization of biopharmaceuticals. In 2017, Guinevere joined the organization committee of the Netherlands Area Biotech (NLab) Discussion group of CASSS. In 2019, she became a member of the scientific committee of the glycomics session, and a member of the early career committee, of MSACL EU. Her research interests are focused on bringing together researchers from the field of biomarker discovery with clinical laboratory professionals, ensuring a better translation of potential biomarkers to the clinic. Moreover, she is dedicated to convincing her fellow colleagues that glycosylation is an important subject and should not be neglected just because it is rather complicated.
Anna Nicolaou, BSc PhD CChem FRSC
The University of Manchester
Julien Boccard, PhD
University of Geneva
Simon Cameron, BSc PhD
Queen's University Belfast
I currently hold an appointment at Queen’s University Belfast as a Vice-Chancellor’s Fellow (lecturer-equivalent position) where my group applies mass spectrometry and microbiology techniques to the direct-from-specimen diagnosis of pathogens and in the analysis of host-microbiome and early-life nutrition-microbiome interactions. I received my BSc (2011) and PhD (2015) from Aberystwyth University, Wales, UK in the area of molecular microbiology and metabolomics. I previously coordinated the work of the MicrobeID team within Professor Zoltan Takats’s research group at Imperial College London, which developed rapid evaporative ionisation mass spectrometry (REIMS) as a high-throughput platform to assign taxonomic and functional classifications to microbial isolates and to the direct-from-sample profiling of mixed microbial communities.
Renee Ruhaak, PhD
LUMC
Renee Ruhaak holds a PhD from the Leiden University Medical Center (LUMC, supervisor Prof. M. Wuhrer) and did a post-doc at UC Davis in the lab of Prof. C.B. Lebrilla prior to joining the department of Clinical Chemistry and Laboratory Medicine at the LUMC. She is currently an associate professor with a research focus on the application of mass spectrometry within the clinical setting. This entails both development and implementation of quantitative protein mass spectrometry, as well as the role of mass spectrometry in metrology and test standardization.
Christophe Stove, PhD
University of Ghent
Christophe Stove graduated in 1999 as a Pharmacist at Ghent University. From 1999 to 2003 he did his PhD in the Laboratory of Experimental Cancerology in the Faculty of Medicine at Ghent University, followed by a post-doc in the Department for Molecular Biomedical Research in the Faculty of Sciences at Ghent University-VIB and -from Oct 2007 on- a Doctor-Assistant position in the Laboratory of Toxicology.
In February 2013 he became tenure-track assistant professor in the Faculty of Pharmaceutical Sciences and since October 2014 he is in charge of the Laboratory of Toxicology.
His activities include education, service (forensic toxicology and reference measurement services) and research. Research fields of special interest are alternative sampling strategies, the deployment of bio-analytical strategies for steering vitamin research and various aspects of G-protein-coupled receptors (GPCR’s).
Ólöf Gerður Ísberg, MSc, PhD
Vanderbilt University, MSACL Early Career Network
Ólöf Gerður Ísbert is a postdoctoral researcher at Vanderbilt University where she works on mapping the whole molecular atlas of the kidneys using IMS and microscopy.. She earned a PhD in Pharmaceutical Science from the University of Iceland in 2021, with work on the project being conducted in London as a collaboration with Imperial College London. The thesis topic was metabolic identification in FFPE breast cancer using DESI-MSI.
Ólöf obtained her B.Sc. at University of Iceland in Biochemistry with focus on molecular biology. She achieved her M.Sc. at University of Copenhagen (Denmark) in Human Biology, with focus on cellular and molecular biology. She has 3 years experience working as a research assistant for both University of Iceland and University of Copenhagen as well as she did a short-term internship at the Danish pharmaceutical company, Lundbeck.
Ólöf is one of the leads of the MSACL Early Career Network (MSACL ECN).
Andrew Davison, PhD
Royal Liverpool University Hospitals
Presented by MSACL EU Scientific Committee members, this address will provide an overview of the applications and technologies currently being used in Clinical Labs, and a clear view of the development pipeline. It will highlight applications expected to be available in the near-future, as well as emerging applications, and key contributors. Relevant talks, posters, and people present at the congress will be identified, enabling you to optimize your learning path and more effectively target potential network connections. Whether you are new to Clinical Mass Spectrometry, or a seasoned veteran, the State of the Science address should be on your agenda.
MALDI-TOF Mass Spectrometry in Clinical Microbiology
Markus Kostrzewa, PhD
Bruker
Dr. Markus Kostrzewa is currently the Senior Vice President of Microbiology & Diagnostics R&D, Regulatory Affairs and Scientific Affairs at Bruker. He completed his PhD in 1993 at the Justus-Liebig-University in Giessen Germany, and his post-doc at the institute of Human Genetics in 1997. He joined Bruker in 1998, where he developed DNA analysis by MALDI-TOF mass spectrometry, Clinical Proteomics methods, consumables and software for mass spectrometry profiling of body fluids and tissues, and microorganism identification by MALDI-TOF mass spectrometry, which is produced and marketed by Bruker under the brand name, MALDI Biotyper.
Already at the end of the last century, MALDI-TOF mass spectrometry protein profiles were proposed as specific fingerprints for microorganisms which can be used for their unequivocal identification by comparison of dedicated reference databases. Nevertheless, it took a further decade until the technology entered routine diagnostic laboratories, suddenly considered as a revolution in microbiology diagnostics. After introduction into the first routine laboratories, it took only a few. years until it became the new microbial identification standard.
A prerequisite of success was the offering of a comprehensive system, a package consisting of the mass spectrometer including user friendly software for data acquisition, interpretation and report, reference databases, standard procedures, and consumables. Reliable service for the instrument and software, but also application support had to be offered to gain confidence of microbiologists and lab technicians in the novel technology. Regulatory approvals are prerequisite for diagnostic in most countries. This could only be achieved by companies who took over the central responsibility for the new diagnostic system.
Three main arguments made MALDI-TOF MS successful, being faster, better and more cost-effective than the previously applied techniques, i.e. biochemical and other phenotypical tests. Superior quality of MALDI-TOF based identification was demonstrated already with early versions of reference databases. Over the years, the libraries for different organism groups have been significantly expanded, today covering thousands of species from different microorganism groups. Species previously not considered to be pathogenic for humans have been detected as causative for infections, and even new microbial species have been discovered. Time to identification has been shortened by at least one day, and even more for slow-growing organisms and for microbes isolated directly from positive blood cultures. Although the initial investment for a MALDI-TOF instrument is considerably higher than for former standard identification systems, the very low running costs make it more cost-effective at least for medium and high throughput laboratories.
While MALDI-TOF is undisputed as the standard routine identification tool for microbiology laboratories, further applications have been proposed which might increase the value of MALDI-TOF MS for clinical microbiology. The considerable diversity in mass spectra that can be observed for many species was proposed for subtyping and epidemiology purposes. Several different approaches have been published for antibiotic resistance or even susceptibility testing. A first IVD-CE marked test for detection of a resistance mechanism has been introduced. Simple detection of specific marker peaks in the mass spectra enables detection of particular strains exhibiting antibiotic resistance. Other procedures comprise the observation of incorporation of isotope-labelled nutrients or the semi-quantitative determination of microbial biomass for susceptibility testing. Recently, besides proteins also lipids get into the focus of MALDI-TOF MS analysis as specific markers, for resistance detection as well as for identification or typing purposes.
My talk will describe the evolution of MALDI-TOF mass spectrometry in the microbiology lab, the conditions for its success and status of today, and I will give an outlook for its future potential.
Dr. Ginsberg is an Assistant Professor of Medicine at the University of California, San Diego. He is a nephrologist with funding from the NIDDK to study the relationship fo vitamin D metabolites and vitamin D binding protein with clinical outcomes. Additionally, he is the PI on a phase-1 trial evaluating advanced imaging techniques for diabetic nephropathy. He also directs the bone biopsy for histomorphometry program at UCSD.
Breakout Room*: KURA biotech
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Seminar
There is no cost to register for this activity.
Exploring host-microbiota co-metabolism
Daniel Globisch, PhD
Uppsala University
Daniel Globisch studied Chemistry at the Technical University of Kaiserslautern (Germany) and the University of Southern Denmark, Odense (Denmark). He received his Ph.D. from the Ludwig-Maximilians-University Munich (Germany) with Professor Thomas Carell in 2011 and joined the laboratory of Professor Kim D. Janda at The Scripps Research Institute (CA, USA) for his postdoctoral studies. He started his independent career in 2015 at Uppsala University (Sweden) as a Science For Life Laboratory Fellow and was appointed as Associate Professor in 2017. He received tenure in December 2020 and was promoted to Full Professor in November 2023. Daniel has been elected as a board member of the Nordic Metabolomics Society and is an Editorial Board Member for the metabolomics society journal Metabolites. The interdisciplinary nature of the research projects is focused on the elucidation of the metabolic interaction between the gut microbiota and their human host. His laboratory develops new Chemical Biology tools to extend the scope of metabolomics research for discovery of unknown biomarkers and bioactive metabolites.
One of the most exciting scientific developments in the past decade has been the understanding that gut microbiota profoundly impact human physiology. The complex consortium of trillions of microbes possesses a wide range of metabolic activity. This metabolic interspecies communication represents a tremendous opportunity for the discovery of unknown bioactive molecules as only limited information on this co-metabolism has been elucidated on a molecular level. Mass spectrometry-based metabolomics analysis is the method of choice for the analysis of known and discovery of unknown metabolites. Chemical Biology tools are still limited in metabolomics compared to other
A native of Florida, Kelly completed her undergraduate studies in Chemistry at the University of Florida. After graduating with honors in 2009, Kelly joined the Department of Chemistry at Vanderbilt University as a graduate student. Her research in the lab of John A. McLean focused on the development of ion mobility-mass spectrometry (IM-MS) methods for the identification of metabolite, lipid, and peptide biomolecular signatures of disease from complex biological samples. After receiving her Ph.D. in 2014, Dr. Hines completed a one-year postdoctoral fellowship in the Mayo Clinic Regional Metabolomics Core where she established quantitative MS methods for lipidomics and protein metabolism using isotope labeling. In 2015, Dr. Hines joined the lab of Libin Xu at the University of Washington. Her work in the Xu Lab focused on the development of IM-MS methods for lipidomics, high-throughput IM-MS measurements of drugs and small molecules, and the significance of lipids in human diseases, environmental exposure and antibiotic resistance. Kelly has authored research publications in top-tier analytical chemistry and molecular sciences journals such as Analytical Chemistry, Journal of Lipid Research, and Molecular Cell. Kelly has been the recipient of several noteworthy awards, including a U.S. Pharmacopoeia Fellowship, the ACS Dan Su Travel Award, and several Young Investigator travel awards. She is most proud of being selected as a Finalist for the University of Washington Graduate School Postdoc Mentoring Award during her time at UW. Outside the lab, Kelly is an avid reader of fiction, a college football enthusiast and enjoys being outdoors.
Christian Freeman, B.S. in Chemistry
University of Georgia
I'm currently a second-year graduate student in the Hines lab at the University of Georgia. My focus now is looking into lipid composition variability caused by external growth factors or gene mutation using reversed-phase liquid chromatography mass spectrometry.
Hannah Hynds, B.S. in Chemistry
University of Georgia
I graduated from Samford University in Birmingham, Alabama in spring 2020 with a bachelor’s degree in chemistry and biochemistry and joined UGA’s Chemistry Ph.D. program in the fall of 2020. As an undergraduate, I worked on organometallic research involving transition metal catalyzed synthesis reactions. Now as a member of the Hines lab, my research focuses on high-throughput flow-injection mass spectrometry and lipid isomer identification through determining carbon-carbon double bond location via ion-mobility.
Our goal is to better understand the ways in which lipids and small molecules contribute to diseases affecting human health and use this knowledge to develop diagnostic and prognostic tools based on molecular signatures of the disease. To achieve this, the Hines Lab develops and applies bioanalytical methods using ion mobility-mass spectrometry (IM-MS) to enhance the throughput and dimensionality of lipidomics and metabolomics experiments. One focus of the group is antibiotic resistance, where we are characterizing the metabolic alterations in antibiotic resistant pathogens and developing IM-MS methods for antibiotic susceptibility testing and small molecule screening.
Resolving diagnostic isomeric lipids with Liquid Chromatography, Ion Mobility Spectrometry and
Tandem Mass Spectrometry
Ahmed Hamid, PhD
Auburn University
Dr. Hamid's PhD studies in Prof. M. Samy El-Shall’s research laboratory in Virginia Commonwealth University were focused on studying ion-molecule kinetics, thermochemistry, and structures using drift tube ion mobility spectrometer measurements associated with quantum mechanics calculations. Then, Ahmed joined Purdue University to work under the supervision of Prof. R. Graham Cooks where he focused on the applications of mass spectrometry to various biological systems, in particular on differentiation of microorganisms using various ambient ionization techniques coupled to mass spectrometry which resulted in novel approaches in the ionization and the identification of bacteria and fungi with high prediction rates without sample preparation. To learn new skills, Dr. Hamid joined the team of Dr. Richard D. Smith in Pacific Northwest National Laboratory to work on the development of novel Structures for Lossless Ion Manipulations (SLIM) which allows previously unattainable ion mobility resolution and remarkable ion manipulations. Moreover, as a senior scientist in MOBILion Systems, Ahmed transferred and further developed the SLIM technology. In summary, Dr. Hamid has more than 14 years of experience researching in the fields of technology development and the applications of mass spectrometry and ion mobility spectrometry which resulted in more than 29 peer-reviewed publications in high impact journals and 7 patents.
CDC estimates that each year 48 million people get sick from a foodborne illness where 128,000 are hospitalized leading to 3,000 deaths. They are caused by pathogenic bacteria, parasites, or viruses that enter the body through the consumption of contaminated food or beverages followed by growth inside the host body. Therefore, rapid methods are crucial for the effective detection of foodborne pathogens in food products to provide safe food supply and to prevent outbreaks of foodborne diseases and the spread of foodborne pathogens. In addition, developing fast robust diagnosis techniques will increase the recovery rates of patients suffering from foodborne infections and will lead to reduced antibiotic resistance.
The membrane of these bacteria contains varying lipid composition that can be utilized as diagnostic biomarker for foodborne disease diagnosis. However, their full characterization remains analytically challenging due to their enormous structural diversity and complexity (e.g., varying acyl chain positions and/or double bond geometries). This presentation will demonstrate the advantages of interfacing liquid chromatography and structurally-based ion mobility with tandem mass spectrometry in the resolution of isomeric lipids. Moreover, this presentation will demonstrate the developments of ambient ionization techniques when coupled to high-resolution ion mobility spectrometry. We expect these developments to enable portable diagnosis devices that can be used for sensitive detection and superior separation power in the analysis of contaminated food samples and foodborne clinical samples without any prior sample preparation. This will enable high throughput analyses that is affordable and can be performed by less-skilled users, such as nurses and farmers.
Fireside Chat on Networking and Career choices with Dr Vera Ignjatovic
Vera Ignjatovic, PhD
Murdoch Children's Research Institute
Professor Vera Ignjatovic is a medical researcher focused on improving outcomes for children. She leads the Haematology Research team at the Murdoch Children’s Research Institute and is a pioneer in the field of paediatric thrombosis and haemostasis and specifically Developmental Haemostasis, the concept describing age-specific development of the haemostatic system. Her research highlights include: First to describe differences in fibrin clot structure in children compared to adults; and first to demonstrate age-specific differences in response to heparin. Vera is an international expert in plasma proteomics, an approach that she uses widely in her research.
In this session, we will discuss:
1. The role of networking for scientists,
2. What are the dos and donts of networking?,
3. Career paths and making the choice,
4. Leadership role and building collaborations,
5. Beyond science and community participation.
Oleg Karaduta, MD University of Arkansas for Medical Sciences
Pankaj Dwivedi, PhD Genentech
Understanding X-Chromosome Deletion Disorder using metabolomics and lipidomics
Hoda Safari Yazd
University of Florida, MSACL Early Career Network
Hoda Safari Yazd is a Ph.D. candidate in analytical chemistry at the University of Florida and working under the supervision of Prof. Richard Yost and Dr. Timothy Garrett. She received her B.Sc. in chemistry from Sharif University of Technology in 2015 and her M.Sc. in computational chemistry from the same school in 2017. Hoda's research at UF primarily focuses on combining analytical chemistry tools and scientific programming for the metabolomic discovery of rare disorders. She is currently working on two projects; the first project concentrates on the detection of new biomarkers in meningiomas to improve early detection of this disease by employing machine learning as a tool on mass spectrometry-based metabolomics data. The second project is focused on the characterization of rare X-chromosome deletion disorders using metabolomics and lipidomics workflows by UHPLC-HRMS on neural progenitor cells. Hoda is one of the founding members and main organizers of the MSACL Early Career Network (MSACL-ECN).
Tim Garrett, PhD
University of Florida College of Medicine
Dr. Garrett has over 20 years of experience in the field of mass spectrometry spanning both instrument and application development. He received his PhD from the University of Florida, under Dr. Richard A. Yost, working on the first imaging mass spectrometry-based ion trap instrument. He has also developed MALDI-based approaches to analyze proteins in bacteria and small molecules in tissue specimens. His current interests include the translation of LC-HRMS, MALDI, DESI and LMJSSP in metabolomics to clinical diagnostics. He is an Associate Professor in the Department of Pathology at the University of Florida, and an Associate Director for the Southeast Center for Integrated Metabolomics (SECIM).
Hoda Safari Yadz and Tim Garrett, from the Garrett lab in Florida, join us today for a presentation and discussion of their work on the metabolomic and lipidomic characterization of an X-chromosome deletion disorder in neural progenitor cells, hosted by the JMSACL podcast group.
X linked disorders are considerably rare and research analysing human samples is under-
represented. Research undertaken in this study used neural progenitor cells from an afflicted patient to begin exploring this rare disorder. While most experimental work focuses on the
neurodevelopmental impacts of X-chromosome associated diseases, this work demonstrates that
they should also be considered metabolic disorders owing to their perturbations on metabolite and
lipid biochemistry. This work aims to use mass spectrometry to improve our understanding of these
conditions and guide novel interventions by characterizing disease associated metabolic alterations.
The Detection of Ethyl Glucuronide in Human Umbilical Cord Tissue using Laser Diode Thermal Desorption-Tandem Mass Spectrometry (LDTD-MSMS)
Joseph Jones, PhD
USDTL
Joseph Jones has worked in the clinical forensic toxicology field for over 30 years for large workplace drug testing laboratories and boutique forensic laboratories that specialize in testing alternative specimen types and is currently the Chief Operating Officer and Executive Vice President of United States Drug Testing Laboratories. He has contributed to over 25 peer-reviewed scientific papers in the field of forensic toxicology and facilitated numerous workshops and presentations. Jones has provided drug testing expert testimony on behalf of LabCorp and USDTL in a number of venues including union arbitration, unemployment hearings, family court child custody, child abuse/neglect and capital murder cases. Jones has been certified by the National Registry of Certified Chemists at a Toxicological Chemist.
Andre Sukta, MSFS
USDTL
Andre Sukta joined USDTL in early 2013 as our Laboratory Supervisor, bringing more than a decade of forensic toxicology expertise with him.
Andre received his Bachelor of Science degree in Chemistry (Forensics concentration) in 2002 from Benedictine University, Lisle, IL. In 2009, he received his Masters of Science degree in Forensic Science from University of Illinois at Chicago. He has co-authored several peer-reviewed research articles, including papers in the Journal of Analytical Toxicology and Forensic Science International.
In 2002, Andre began his career in toxicology as a Forensic Scientist with the Illinois Racing Board Laboratory. Since then, he has worked with various toxicology groups, including University of Illinois at Chicago - College of Pharmacy, Indiana University - College of Medicine, and the Indiana State Department of Toxicology.
Andre Sukta is a member of the Society of Forensic Toxicologists (SOFT), where he serves as a director of the organization, and serves on the professional mentoring program committee. He is also a member of the National Safety Councils Alcohol, Drugs and Impairment Division, where he serves as the Cannabis and Health and Safety subcommittee chair. He is also a full member of the American Academy of Forensic Sciences (AAFS), Chicago Chromatography Discussion Group (CCDG), and Midwest Association of Toxicology and Therapeutic Drug Monitoring (MATT).
Prenatal exposure to ethanol has long been associated with several long-term negative health consequences for the newborn including physical, cognitive, social, and behavioral impairments. The prevalence of FASD in North America may be as high as 5% of the population which represents an enormous public health concern (Flannigan, Coons-Harding, Anderson, Wolfson, Campbell, Mela, & Pei, 2020). Early identification of those affected is critical to address the special needs of these children to improve their outcomes. Outside of maternal self-report, there are limited strategies to objectively identify PAE at or near the time of birth.
Current testing strategies to detect prenatal exposure to ethanol is limited in scope and utility Unfortunately, a rapid immunoassay test does not exist leaving us with a very expensive and time-consuming liquid chromatography tandem mass spectrometry screening method. The objective of this presentation is to demonstrate a newly developed and validated a method for the detection of ethyl glucuronide in umbilical cord tissue using Laser Diode Thermal Desorption-Tandem Mass Spectrometry. The Laser Diode Thermal Desorption (LDTD), allows for a significant decrease in time and expense when compared to the current methodology.
The method was developed and validated according to the guidelines of the Scientific Working Group on Forensic Toxicology. Briefly, Umbilical Cord Tissue was weighed out (0.5 g), deuterated internal standard is added and homogenized in 3 mL of deionized water. Following centrifugation, the supernatant was purified using a solid phase extraction technique. The final reconstituted extract (8
Dr Cristina Legido-Quigley is the Head of Systems Medicine at Steno Diabetes Center Copenhagen and an Associate Professor at King’s College London.
Her main area of interest is neurometabolism and how the brain copes with disease, as well as finding clinical tests for healthy aging, Alzheimer's, cognition, diabetes and metabolic diseases. Her discoveries span fatty molecules that are important for cognition, small molecules that in liver alert to tissue damage, together with modulating molecular pathways for improving the treatment of diabetes. She is also researching algorithms for better personalised diagnoses in the clinic.
She has been a group leader at King's College London since 2006. In 2018 she moved to Steno a hospital and research center in Denmark to pursue her interests in Systems Medicine. She shares her findings in scientific publications in the biotechnology and medical fields
Naba Al-Sari, Ph.D. Candidate
Scientist passionate to improve patient care via novel biomarkers & precision medicine
Karolina Sulek, PhD, MSE
Steno Diabetes Center Copenhagen
I had the pleasure to learn from the best in the field in metabolomics, lipidomics and proteomics. My primary interest is translating these technologies into the clinical setting for improved, more personalized disease treatment.
My education is a combination of various experiences within technology, mass spectrometry and clinical applications:
MSE from the Technical University of Warsaw (Poland)
PhD from the Technical University of Denmark (Denmark)
Postdoctoral research at the University of Auckland (New Zealand) and University of Copenhagen (Denamrk)
Short-term visits at the University of Campinas (Brazil), University of Alberta (Canada), Max Planck Institute of Biochemistry (Germany)
Asger Wretlind, M.Sc.
Steno Diabetes Center Copenhagen
University of Copenhagen
His PhD project looks into individual metabolic response to diabetes treatments and investigate biomarkers that can be used to direct personalized treatment.
Jin Xu, PhD
King's College London
Dr Jin Xu is a Research Associate at King's College London. Her research focuses on the application of metabolomics and lipidomics to understand the underlying biology in Alzheimer's disease, together with the integration of multi-omics and clinical data to test early diagnostic panels.
Tommi Suvitaival
Steno Diabetes Center Copenhagen
I am a data scientist with a background in machine learning and computational sciences, and a specific focus in digital human health.
I am affiliated with the Systems Medicine research group at Steno Diabetes Center Copenhagen, where I work as a bioinformatics and biostatistics specialist to process, analyze, visualize and understand complex omics data from the small molecule profiling platforms managed by the team.
Andressa de Zawadzki, PhD
Steno Diabetes Center Copenhagen
Postdoctoral researcher at Steno Diabetes Center. Currently working with the use of state-of-the -art mass spectrometry-based metabolomics to investigate gut-and-liver axis in alcoholic liver fibrosis, in collaboration with SDU through GALAXY project. Andressa did a PhD in the field of metabolomics at the University of São Paulo and University of Copenhagen. She worked 2 years as a postdoc in the department of Food Science at the University of Copenhagen.
Our research goal is to discover clinical tests for diagnostics and new disease treatments. We work on neuro and metabolic diseases and particulalrly in disease that affects the brain and the liver, like Alzheimer's Disease and Diabetes.
Our science is at the interface between chemistry and medicine and we are experts in biotechnology and the use of data science to allow the detection of thousands of small molecules / lipids in order to understand the underlying biology in disease.
We can get molecular data with mass spectrometry instruments and perform data analytics, including machine learning, to understand this biology. In order to translate results into the clinic we also work with clinical trials and evidence portfolios for EMA approval. This field of research can be called systems medicine, because it integrates -omic data and clinical data together to understand health.
Lab Showcase meetings are opportunities for lab PIs and Directors to share their scientific goals and ambitions, and introduce the labs' current projects and scientists to our community. This provides opportunities for
(1) identifying potential points of collaboration, and
(2) engaging with early career and underrepresented scientists.
Interactive career development fireside chat with Dr. Anne Bendt
Anne K. Bendt, PhD
Singapore Lipidomics Incubator (SLING), National University of Singapore
Anne K Bendt studied Biology focusing on marine biotechnology (Greifswald University, Germany), followed by a PhD in Biochemistry (Cologne University, Germany) employing proteomics and transcriptomics. Driven by her fascination for infectious diseases, she joined the National University of Singapore (NUS) in 2004 to develop lipidomics tools for tuberculosis studies. She is now a Principal Investigator at the Life Sciences Institute, NUS, focussing on translation of mass spec technologies into clinical applications, and serving as the Deputy Director of the Singapore Lipidomics Incubator (SLING) taking care of operations and commercialization.
Are you thinking about the next step in your career? About an international career move? Publishing your exciting scientific findings in an Open Access journal? Don
Department of Urology, Graduate School of Medicine,
Kyoto University, Japan
Dr. Xin Li is a research fellow at the Department of Urology, Graduate School of Medicine, Kyoto University where he got his Ph.D. degree. He is going to start to work at Peking University Third Hospital as a urologist in August 2021. Dr. Li is also proud to win the Young Investigator Grant in MSACL EU 2019 and to have a podium presentation of his research there. Recently, he has become a member of the Japanese Society for Biomedical Mass Spectrometry (JSBMS). While studying at Kyoto University he became interested in the clinical application of MALDI-TOF/MS, especially when using it in the urinary lipid analysis. Dr. Li and his supervisors, especially Dr. Kenji Nakayama who is an Asia Outreach Committee of MSACL and also one of the JSBMS council members, developed a simple relative-quantitative MALDI-TOF/MS system for urinary lipidomics, and they are applying it in the screening of urinary biomarkers for genitourinary disorders. Now, they are aiming at promoting the "qShot MALDI” system as a simple application for the MALDI analysis.
Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) has been used for lipid analysis since the 2000s. However, the poor reproducibility and quantitative ability hinder its application in clinical biomarker screenings. To improve the clinical usage of MALDI-TOF/MS, especially for quantitative detection of the urinary phospholipids (PLs) and lysophospholipids (LPLs), we have adopted three main strategies including the selection of a proper matrix, a specially designed plate, and a spike of ionization standards. This system, named
Lab Showcase: Kari Basso, her Science, and her Lab
Kari Basso, PhD
University of Florida
I have extensive (26 years) experience in advanced mass spectrometry and advanced biological/lipidomic/metabolomics/proteomic applications. As Director of the UF Mass Spectrometry Research and Education Center (MSREC), I administer the day-to-day activities, analyze more complex data sets, supervise the complex mass spectrometry experiments, generate proposals for additional new instruments and upgrades, and interact with faculty to ensure that analytical needs are met in the most efficient way possible. I have a very broad experience in mass spectrometry (Orbitrap, QTOFs, Ion Traps, Triple quadrupoles, GC-MS, FT-ICR, ESI, MALDI, and various bioinformatics platforms). I also have a very broad expertise in applications including biological, environmental, polymer, lipidomic, glycomic and proteomic applications with over 90 publications to date. I completed my graduate work at Louisiana State University under the direction of Dr. Patrick A. Limbach (currently at the University of Cincinnati). I served as The Ohio State University Mass Spectrometry and Proteomics Facility Director (OSU MS&P) for 15 years where I had considerable experience in identifying proteins and protein modifications, lipids, metabolites, and carbohydrates for quantitative analysis and identification of biomolecules. I have previously published under K.B. Green-Church and K.B. Green before transitioning to K.B.Basso.
Laura Bailey, PhD
University of Florida, Department of Chemistry
I received my BS in Chemistry in 2013 working in gas phase kinetics with Dr. David Dolson at Wright State University in Dayton, Ohio. Working with Dr. Nicolas Polfer at the University of Florida in Gainesville, Florida, I earned my PhD in Analytical Chemistry in 2019. I was part of the team developing the first mass selective cryogenic linear ion trap for performing ion spectroscopy. Additionally, my dissertation research focused on characterizing phosphopeptides using several mass spectrometric methodologies, including low energy collisional activation and laser induced activation schemes as well as ion spectroscopy. Upon completion of my graduate studies, I working collaboratively with Dr. Guo and Dr. Basso in the Mass Spectrometry Research and Education Center as a post doctoral associate to develop their lipidomic analytical methods. I have developed and optimized LC-MS(MS) methodologies for untargeted lipidomic analysis, including developing a quantitative assay for improved unlabeled lipid quantitation and creating a methodology to characterize glycolipids using in vitro MSMS pattern matching. In 2021, I was hired as a Chemist to continue in the Mass Spectrometry Research and Education Center under the direction of Dr. Kari Basso to continue working on lipidomic systems and to manage the Polymer Chemical Characterization Laboratory in collaboration with Dr. Brent Sumerlin.
Manasi Kamat
UNIVERSITY OF FLORIDA
I earned my PhD in Chemistry in 2015 at University of Florida under Dr. Richard Yost and Dr. Kevin Wang. My research focused on identifying protein biomarkers for traumatic brain injury (TBI). While working on my research, I had a great opportunity to be a teaching assistant in MSREC lab. This gave me an exposure to work on different types of mass spectrometers. After my defense, I was hired as a post doc in this facility under Dr. Kari Basso. During this time, I have worked on number of projects that includes label free proteomics, LC-MS/MS method development, lipidomics, small molecules, etc. In 2018, I was offered a Chemist position in MSREC lab. I currently look over majority of the projects that includes proteomics, targeted analysis, metabolites, lipids, etc. Being in the service lab, I also assist in training clients in sample prep, data analysis and also on using the instruments. I am also responsible for maintenance and troubleshooting of all the mass spectrometers in the lab.
Subhradeep Bhar, MS
University of Florida
I am a fifth year PhD student at the Department of Chemistry, University of Florida. I have received my Master’s Degree in Pharmaceutical Chemistry from Birla Institute of Technology, India. My current research is focused on discovering novel natural products produced by roundworm Caenorhabditis elegans using mass spectrometry and comparative metabolomics techniques.
Alexandra Wolfer, Bachelor of Science in Chemistry
University of Florida
Lab Showcase meetings are opportunities for lab PIs and Directors to share their scientific goals and ambitions, and introduce the labs' current projects and scientists to our community. This provides opportunities for
(1) identifying potential points of collaboration, and
(2) engaging with early career and underrepresented scientists.
Supported by an Open Unrestricted Educational Grant
provided by
There is no cost to register for this activity.
Get the Basics: Toxicology Primer
Paul Jannetto, Ph.D., DABCC, FAACC, M.T.(ASCP)
Mayo Clinic
Paul J. Jannetto, Ph.D., DABCC, FAACC, M.T.(ASCP), is an Associate Professor in the Department of Laboratory Medicine and Pathology and a Consultant at the Mayo Clinic (Rochester, MN), where he serves as the Co-Director for the Clinical Mass Spectrometry Laboratory, Clinical and Forensic Toxicology Laboratory and the Metals Laboratory. Previously, he was an Associate Professor of Pathology at the Medical College of Wisconsin (Milwaukee, WI) where he functioned as the Director of Clinical Chemistry/Toxicology at Dynacare Laboratories (Milwaukee, WI). He earned his BS in Clinical Laboratory Science from the University of Wisconsin-Milwaukee and worked five years as a Medical Technologist for Medical Science Laboratories before entering graduate school. He then earned a Ph.D. in Pharmacology and Toxicology at the Medical College of Wisconsin. He is board-certified by the American Board of Clinical Chemistry and American Society for Clinical Pathology. His clinical and scientific interests are centered on Clinical & Forensic Toxicology, Therapeutic Drug Monitoring, and Elemental Analysis.
Dr. Jannetto has been actively involved in the American Association for Clinical Chemistry (AACC) where he has participated in the TDM/Toxicology, Mass Spectrometry and Separation Sciences, Molecular Pathology, Management Sciences and Patient Safety, Personalized Medicine, and Critical and POCT divisions. In the past, he has served on numerous positions at the local level in both the Chicago and Midwest sections (e.g. Chair of the Chicago Section, Secretary of the Chicago Section, and Treasurer of the Midwest Section of AACC), and at the national level as a member of the Governance Review Advisory Taskforce, NACB Board of Directors, AACC Board of Directors, and Chair of the House of Delegates. Dr. Jannetto is also a member of the American Academy of Pain Medicine, International Association of Therapeutic Drug Monitoring and Clinical Toxicology, and was the President of the Midwest Association for Toxicology and Therapeutic Drug Monitoring. He has over 50 peer-reviewed publications, 14 book chapters, and over 75 abstracts/presentations at various national meetings.
An overview of the fundamentals that are driving research and development in the field of Toxicology.
This is part of a series of Primers on topics relevant to Clinical Mass Spectrometry.
Learning objectives include:
1. Be able to define what Toxicology is, why it matters, and why you personally should care. What is the clinical relevance?
2. Understand what role mass spectrometry plays in this field. Where does mass spec fit in to the big picture of the field?
3. Define any terminology that is specific to this field.
4. Describe how it works, what are the methods and workflows used when studying this field and/or how is it implemented in clinical labs.
5. Identify any challenges to implementation/adoption, where do the opportunities lie?
Alan Rockwood, PhD, DABCC University of Utah, School of Medicine
How to Write a Great Research Paper, and Get it Accepted by a Good Journal
Anthony Newman
Elsevier
Anthony Newman, who is making the presentation today, is a Senior Publisher with Elsevier, and is based in Amsterdam. Currently responsible for sixteen laboratory medicine and biochemistry journals, he joined Elsevier over 30 years ago and has been Publisher for the last 20+ years. Before then he was the marketing communications manager for the biochemistry journals of Elsevier. By training he is a polymer chemist and was active in industry before leaving London and moving to Amsterdam in 1987 to join Elsevier.
Tamas Pongracz, PhD Leiden University Medical Center
The Role of Mass Spectrometry in the Study of Respiratory Diseases: Fireside Chat with Prof. Craig Wheelock about his research and career development.
Craig Wheelock, PhD
Karolinska Institute
Craig E. Wheelock is an Associate Professor in the Department of Medical Biochemistry and Biophysics at the Karolinska Institute, Sweden, where he serves as director of the Integrative Molecular Phenotyping Laboratory (www.metabolomics.se). He is also a Distinguished Visiting Professor of Metabolomics at Gunma University, Japan. Following post-doctoral work on lipid mediators at the University of California Davis, he conducted additional post-doctoral studies at the KEGG laboratory in Kyoto University, Japan. In 2006, he was awarded a Marie Curie Fellowship to relocate to the Karolinska Institute. Research in his group focuses on molecular sub-phenotyping of respiratory disease, with a particular area of interest in investigating the role of eicosanoids and other lipid mediators. The overall aim is to develop personalized molecular profiles that can be associated with an individual’s lifestyle, environmental exposure and susceptibility to disease onset. He has been a founding Board Member of the Nordic Metabolomics Society since 2017, a Board Member of the International Metabolomics Society from 2016-2020, and serves on the European Respiratory Society (ERS) Advocacy Council as the Director of Scientific Relations with the EU. When not balancing his time between Sweden and Japan, he enjoys teaching his kids to kayak and play nicely with others.
"Mass Spectrometry has demonstrated to be a powerful analytical tool for the study of multiple diseases! This month, we will talk with Prof. Craig Wheelock about the application of MS-based approaches in the understanding of the pathophysiology of inflammatory respiratory diseases. His group is focused on the targeted analysis of lipid mediators (e.g., eicosanoids, sphingolipids) and investigating their role in the etiology of inflammatory disease.
Join our Career Fireside chat to learn from Prof. Craig Wheelock about his projects as well as his stories, lessons and advice on career paths in mass spectrometry. This is an interactive event and there will be an opportunity to chat and network with Craig and other attendees."
Novel In-Sample Calibration Curve (ISCC) with Multiple Isotopologue Reaction Monitoring (MIRM) for Quantitative LC-MS/MS Bioanalysis
Huidong Gu, MS
Bristol-Myers Squibb
Mr. Huidong Gu is a Principal Scientist in the Clinical Biomarker Immunoassays and Mass Spec Department at Bristol-Myers Squibb Company. For the past 17 years, Huidong has been working in the area of LC-MS/MS bioanalysis of small molecules, biologics and biomarkers with over 30 peer-reviewed publications. Huidong developed a novel approach for calculating and mitigating isotopic interferences in LC-MS/MS quantitative analysis. This approach has a significant impact in the area of microdosing absolute bioavailability studies using LC-MS/MS analysis of both the oral dosed non-labeled drug and the IV microdosed stable labeled drug. His recent work of in-sample calibration curve (ISCC) with multiple isotopologue reaction monitoring (MIRM) technique allows the instant and accurate measurement of biomarkers, biotherapeutics and small-molecule drugs in biological samples without using external calibration curves. This methodology can bring unique values of eliminated external calibration curves, simplified the workflows and improved throughput in the areas where absolute quantitation and overall sample turnaround still remain great challenges.
External calibration curves are commonly used in LC-MS/MS quantitative bioanalysis. In this presentation, a novel methodology of In-Sample Calibration Curves (ISCC) using Multiple Isotopologue Reaction Monitoring (MIRM) of a SIL-analyte for instant LC-MS/MS bioanalysis will be discussed. The theoretical isotopic abundances of a SIL-analyte in its MIRM channels can be accurately calculated based on the isotopic distributions of its daughter ion and neutral loss. The isotopic abundances in these MIRM channels can also be accurately measured with a triple quadrupole mass spectrometer. By spiking a known amount of the SIL-analyte into each sample, an ISCC can be established based on the relationship between the calculated isotopic abundances and the measured LC-MS/MS peak areas in each sample for the quantitative bioanalysis. With this novel MIRM-ISCC-LC-MS/MS methodology, instant, accurate and reliable LC-MS/MS bioanalysis of biomarkers, biotherapeutics and small molecule drugs can be achieved without using external calibration curves. Moreover, this methodology can bring unique values of eliminated external calibration curves, simplified workflows and improved throughput in the areas where absolute quantitation and overall sample turnaround still remain great challenges. The potential applications in quantitative proteomics, clinical laboratories and other areas will also be discussed.
Novel Techniques using Silicon (in silico) and Gold to Improve Imaging Results
Untargeted small molecule machine learning for MSI
Cameron Shedlock
University of Scranton
Cam has recently discovered mass spectrometry imaging and found a home with data analysis. He hopes to continue MSI development and exploration through the completion of his undergraduate degree and pursue analytical chemistry in graduate school. Cam enjoys time in the outdoors when not camping out behind a computer screen.
Mass spectrometry imaging returns large dimensionally complex datasets. Traditional analysis in imaging utilizes a mindset focused on target molecule identification that parses data with a narrow view of molecular exploration. These data analysis methods are specifically focused on exploring differences between a traditional organic acid matrix when compared to using nanoparticles for MSI, which results in very different ionization of small molecules. Analysis methods have taken a shotgun approach using both supervised and unsupervised machine learning to reveal critical trends in MSI datasets. A workflow is being prepared which enables select regions of interest to be compared using powerful machine learning algorithms to offer a holistic approach to data analysis and class comparison.
Mass spectrometry imaging using gold nanoparticles
Kate Stumpo, PhD
University of Scranton
Kate's primary job is as an educator at a Primarily Undergraduate Institution (PUI). In her spare time, she works with students on mass spectrometry imaging projects.
Mass spectrometry imaging (MSI) is a powerful analytical method for the simultaneous analysis of hundreds of compounds within a biological sample. Despite the broad applicability of this technique, there is a critical need for advancements in methods for small molecule detection. Some molecular classes of small molecules are more difficult than others to ionize, e.g., neurotransmitters (NTs). The chemical structure of NTs (i.e., primary, secondary, and tertiary amines) affects ionization and has been a noted difficulty in the literature. In order to achieve detection of NTs using MSI, strategies must focus on either changing the chemistry of target molecules to aid in detection or focus on new methods of ionization. This presentation will introduce a new method of ionization, using gold nanoparticles (AuNPs), and the bigger picture of NPs for MSI.
Oleg Karaduta, MD University of Arkansas for Medical Sciences
JMSACL Journal Club with Benjamin Owusu : Development and validation of a novel LC-MS/MS assay for C-peptide in human serum
Benjamin Owusu, PhD
Labcorp
Dr. Benjamin Owusu is the Technical Director, Clinical Chemistry at Laboratory Corporation of America (Labcorp), Burlington, NC. He did his postdoctoral clinical fellowship at the University of Washington School of Medicine. Dr. Owusu earned his PhD degree in Biochemistry and Molecular Genetics at the University of Alabama at Birmingham (UAB). He obtained his Bachelor of Science degree in Biochemistry (first class honors) at the University of Ghana, where he also served as a Teaching Assistant. He later moved to Emory University School of Medicine in Atlanta, GA on a visiting research scholarship prior to starting his doctoral training at UAB. Dr. Owusu is a recipient of multiple academic/research awards and honors. His research over the years span across cancer, cardiovascular, hematological, and endocrinological diseases. In addition to clinical service in diagnostics and research, Dr. Owusu is also passionate about teaching and mentoring, particularly in STEM education.
Electrochemical Strategies in ESI-MS for Lipid Analysis
Xin Yan, PhD
University of Texas A&M
Dr. Xin Yan received her Ph.D. in Chemistry from Purdue University in 2015 under the supervision of Professor R. Graham Cooks. After graduation, she did her postdoctoral research with Professor Richard N. Zare at Stanford University.
Dr. Xin Yan joined the chemistry department, Texas A&M University as an assistant professor in the summer of 2018. Her research centers around the development and application of droplet chemistry in lipid/metabolite analysis, reaction acceleration, and new synthetic methods.
Lipids play a vital role in maintaining cellular functions. Altered lipid metabolism is currently considered a hallmark of many diseases, which highlights the importance of the characterization of lipid composition in understanding, diagnosing, and treating pathologies. Discrimination of isomeric species is challenging in lipidomics. In this talk, I will introduce the microdroplet electrochemical methods capable of resolving different types of isomers commonly encountered in lipid samples using electrospray ionization mass spectrometry. The methods take advantage of the voltage-controlled and dramatically accelerated electrochemical derivatization of lipid isomers in microdroplets to achieve structural elucidation. Applications of the electrochemical mass spectrometry methods in real sample analysis will also be included.
Mapping complex lipid biochemistry in tissues using advanced mass spectrometry imaging technologies
Shane Ellis, PhD
University of Wollongong
Shane Ellis completed his Undergraduate studies (B.Nanotechnology) and PhD in the field of ambient ionisation mass spectrometry and lipidomics the University of Wollongong, Australia. In 2012 he began a post-doctoral positional at the FOM-Institute AMOLF where he worked on the development of innovative active-pixel detectors for charged particle detection with applications in imaging mass spectrometry and ion mobility spectrometry. From 2014-2019 he was an Assistant Professor within the M4I Institute (Maastricht University, The Netherlands) where he led the Instrumentation and Application Development Group. His research develops and applies state-of-the-art mass spectrometry imaging methods to reveal localised biochemical processes within complex tissues and how they altered with disease. His group has developed a variety of innovative methods that significantly enhance the sensitivity and spatial resolution of MSI experiments and enabled precise and comprehensive structural identification of the many molecules detected by MSI. This research was supported by numerous Dutch and European grants. In 2020 he returned to Australia as an ARC Future Fellow and started a new mass spectrometry imaging group within the new Molecular Horizons Institute where he continues to further develop and apply mass spectrometry imaging technologies and apply them to challenging biological and chemical problems.
Dr Shane Ellis's group develops and applies mass spectrometry imaging (MSI) technologies to study the distributions of various molecular species throughout tissues and cells. His research covers both the development of new instrumentation to improve the performance of MSI (e.g., sensitivity, spatial resolution and molecular coverage) as well as the application of MSI to studying altered molecular processes occurring in diseased tissues and the spatially-resolved classification of such tissues. A particular focus is in the field of lipidomics, where he applies state-of-the-art MSI technologies to visualize and understand altered lipid biochemistry occurring in diseased tissues and cells.
Reference data-driven metabolomics and application to nutrition research
Pieter Dorrestein, PhD
UCSD
Pieter Dorrestein uses mass spectrometry to eavesdrop on the molecular conversations between microbes and their world. To produce the image, researchers swabbed every surface in the room, including the people, several hundred times, then analysed the swabs with mass spectrometry to identify the chemicals present.
Kiana West, PhD
UCSD
Kiana is currently a post-doctoral researcher in the Dorrestein Lab at UCSD. She is applying a reference data-driven approach to generate food readouts from metabolomics data acquired from clinical biospecimens. These readouts, proxies for diet consumption, are used to investigate interactions between diet, disease, and the gut microbiome. Her primary clinical focus is Inflammatory Bowel Disease (IBD), but she is also involved in other projects such as Alzheimer’s disease. Kiana received a PhD in Clinical Medicine Research from Imperial College London where she studied metabolomics and microbiomics. Her research at Imperial focused on uncovering metabolic/bacterial signatures associated with altered human development, such as adverse pregnancy outcomes and Autism Spectrum Disorder.
Untargeted metabolomics experiments suffer from large proportions of unannotated molecules. Using a reference data-driven approach, we increase the spectral annotation rate by assigning potential sources to molecular features. We have applied this approach using a food reference database to generate diet readouts from clinical samples. Surveying the food-associated compounds detected in clinical samples, we can differentiate patients with specific diet types, such as predominantly animal protein- versus plant-based diet. In addition, we can identify specific foods associated with clinical outcomes in disease cohorts. With its broad applications, we envision this approach becoming invaluable in nutrition research as well as many other fields once additional reference datasets become available.
Catalyzing Scientific Conversation with Post-Publication Review
Renee Williams, PhD MBA
SciBase
A chemist by training, Renee is now the Chief Growth Officer for SciBase, which is the Yelp of scientific literature. She trained as a founder in programs such as YC Startup School and Founder Gym, completed a dual MBA program at Cornell University and Queen's University, and studied venture capitalism at The Wharton School. She has experience in industry as Senior Scientist and Senior Manager of Business Strategy and Operations at Janssen BioPharma.
Kenneth Hallenbeck, PhD
SciBase, Inc
Ken Hallenbeck earned a Ph.D. in pharmaceutical sciences from the University of California, San Francisco, and now is an early drug-discovery researcher. He loves to think and write about the future of scientific research. He serves on the board of directors of ReImagine Science, a nonprofit that empowers and connects scientist advocates, and is the life sciences lead at TerraPrime, a consulting firm that works with start-ups that aim to disrupt the scientific publication and education ecosystems.
It has happened to all of us: a paper comes out describing results related to your lab work. You scroll down to the methods to see what they did - a few days or weeks later, you try to replicate the result in your own lab. It doesn
Empirically tracking the exposure of human plasma & serum samples to thawed conditions
Chad Borges, PhD
Arizona State University
Chad Borges is an associate professor at Arizona State University with appointments in the School of Molecular Sciences and The Biodesign Institute. He has a B.S. in chemistry and a Ph.D. in Analytical Toxicology. Though he has extensive experience in quantifying small molecules by mass spectrometry, his research interests currently reside in characterizing and quantifying protein post-translational modifications (PTMs) for biomedical purposes. This includes application of a new form of bottom-up glycomics known as glycan “node” analysis; developing molecular markers of biospecimen integrity; and quantification of PTMs as indicators of disease.
Exposure of blood plasma/serum (P/S) to thawed conditions (> -30
Bini Ramachandran, PhD University of Nebraska-Lincoln
Host Factor Targeted Drug Discovery for SARS-CoV-2 Through an International Collaboration
Nevan Krogan, PhD
UC San Francisco, Gladstone Institutes
Nevan Krogan, PhD, is a molecular biologist, UC San Francisco professor, and director of the intensely interdisciplinary Quantitative Biosciences Institute (QBI) under the UCSF School of Pharmacy. He is also a senior investigator at the Gladstone Institutes.
He led the work to create the SARS-CoV-2 interactome and assembled the QBI Coronavirus Research Group (QCRG), which includes hundreds of scientists from around the world. His research focuses on developing and using unbiased, quantitative systems approaches to study a wide variety of diseases with the ultimate goal of developing new therapeutics.
Nevan serves as Director of The HARC Center, an NIH-funded collaborative group that focuses on the structural characterization of HIV-human protein complexes. Dr. Krogan is also the co-Director of three Cell Mapping initiatives, the Cancer Cell Mapping Initiative (CCMI), the Host Pathogen Map Initiative (HPMI) and the Psychiatric Cell Map Initiative (PCMI). These initiatives map the gene and protein networks in healthy and diseased cells with these maps being used to better understand disease and provide novel therapies to fight them.
He has authored over 250 papers in the fields of genetics and molecular biology and has given over 350 lectures and seminars around the world. He is a Searle Scholar, a Keck Distinguished Scholar and was recently awarded the Roddenberry Prize for Biomedical Research.
Jacqueline Fabius
Quantitative Biosciences Institute
Jacqueline Fabius obtained her undergraduate degree from Hamilton College in Comparative Literature and Spanish. She worked in media and management consulting for 11 years prior to joining the United Nations and later UCSF in the role of the Chief Operating Officer for the Quantitative Biosciences Institute, where she heads a number of initiatives including establishing relationships and collaborations as well as media and communication strategy for the institute. In alignment with QBI’s mission to bring young investigators and women scientists to the forefront at QBI, she started the Scholarship for Women from Developing Nations. Her focus is facilitating communication and networking across wide audiences ranging from scientists to lay audience.
The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease is evolving during the current pandemic. New variants show enhanced replication and the potential to evade therapeutic antibodies. In the near future, variants may even evade first generation vaccines. The currently approved direct acting antiviral remdesivir targets the viral RNA-dependent RNA polymerase which is subject to rapid evolution as it is encoded by the viral RNA genome. In order to develop therapeutic approaches which act in a pan-coronavirus manner we and our colleagues at the QBI Coronavirus Research Group (QCRG) have mapped the human proteins (host factors) which multiple Coronaviruses rely on for replication. Through a rapid drug repurposing effort we have identified zotatifin, a clinical eIF4A inhibitor as a host factor targeted therapeutic. Zotatifin which is based on the natural product rocaglamide A works as a molecular glue to trap eIF4A on its target, the (+) RNA viral genome. Other examples of targeting essential host factors, including those for immune evasion will be discussed.
Transitioning from nanoflow to standard flow LC/MS: High throughput protein biomarker quantification for clinical research
Linfeng Wu, PhD
Agilent Technologies
Liquid chromatography mass spectrometry-based proteomics has been widely used for protein biomarker discovery and validation. When transitioning from discovery proteomics to targeted protein biomarker quantification, the MRM-based LC/MS method plays an important role in clinical research. To ensure analytical reproducibility and robustness, implementing standard flow-based triple quadrupole LC/MS system has tremendous benefit when involving a large cohort. This webinar will discuss the analytical performance under standard-flow and low LC flow conditions using the Agilent 6495 triple quadrupole LC/MS system.
For Research Use Only. Not for use in diagnostic procedures.
ECN Fireside Chat: the Australian MS Industry with Prof Michelle Colgrave & Dr. Richard Lipscombe
Prof. Michelle Colgrave
Edith Cowan University, CSIRO
Michelle Colgrave is a Professor of Food and Agricultural Proteomics in the School of Science at ECU, Australia. She is the Future Protein Lead in CSIRO Agriculture and Food, based at the Queensland Bioscience Precinct in Brisbane, Australia. Prof Michelle Colgrave is using mass spectrometry (MS) and proteomics to help identify key proteins that will benefit Australia's livestock and plant industries and improve human health. Prof Colgrave is working to identify novel proteins and characterise their function and post-translational modifications. Prof Colgrave is a Chief Investigator on the ARC Centre of Excellence for Innovations in Peptide and Protein Science.
Dr. Richard Lipscombe
Proteomics International
Richard Lipscombe is the Founding and Managing Director of Proteomics International. Richard is a protein chemist by training having completed his chemistry degree at Oxford University and a Doctorate in Immunology at London University. Richard moved to Perth in 1995 and managed the Protein Analysis Facility at the University of Western Australia, before stepping out of academia to co-found Proteomics International in 2001.
Richard's career has focused on industry based research and the translation of innovative technology into commercial products and services. He holds several patents and, almost uniquely, has taken a protein biomarker from concept to commercial diagnostic test, with the company's pioneering prognostic test for diabetic kidney disease, PromarkerD, now in the clinic.
From down under, this time we bring you two successful scientists bridging academia and industry: Prof. Michelle Colgrave and Dr. Richard Lipscombe. Prof Colgrave of Commonwealth Scientific and Industrial Research Organisation (CSIRO), Australia focuses on applications of mass spectrometry based proteomics in food and agriculture, while Dr. Lipscombe heads Proteomics International Laboratories Ltd (PILL), an Australian company in the field of clinical mass spectrometry and diagnostics. Come and e-meet these two grand individuals in the Australian mass spectrometry field!
Note the date and time:
Sydney - 2PM Thursday March 26
Auckland - 4PM Thursday March 26
Supported by an Open Unrestricted Educational Grant
provided by
There is no cost to register for this activity.
The Time Has Come for Quantitative Protein Mass Spectrometry Tests That Target Unmet Clinical Needs
Renee Ruhaak, PhD
LUMC
Renee Ruhaak holds a PhD from the Leiden University Medical Center (LUMC, supervisor Prof. M. Wuhrer) and did a post-doc at UC Davis in the lab of Prof. C.B. Lebrilla prior to joining the department of Clinical Chemistry and Laboratory Medicine at the LUMC. She is currently an associate professor with a research focus on the application of mass spectrometry within the clinical setting. This entails both development and implementation of quantitative protein mass spectrometry, as well as the role of mass spectrometry in metrology and test standardization.
Quantitative protein mass spectrometry is a promising, yet complex technology that enables precision diagnostics. It allows for the multiplexed and direct quantitation of analytes at the molecular level, potentially including identification of proteoforms. Therefore, MS based tests are now proposed more and more often. Yet, quantitative protein mass spectrometry is a complex technique, which has hampered its applications. To ensure efficient test development, novel tests should target clinical gaps in the contemporary clinical pathways, and each of five key elements of test evaluation, as identified by the European Federation for Clinical Chemistry and Laboratory Medicine should be considered. Here we present our experience in the development and application of quantitative protein mass spectrometry, and aim to take away the concerns that have kept laboratory medicine from implementing this promising technology.
Getting going with mass spectrometry: Josh attempts method validation
Joshua Hayden, PhD, DABCC, FACB
Norton Healthcare
Joshua is currently the Chief of Chemistry at NortonHealthcare. He earned his PhD in chemistry from Carnegie Mellon University. He conducted postdoctoral research at Massachusetts Institute of Technology before completing a two-year clinical chemistry fellowship at University of Washington and 4 years as Assistant Professor at Weill Medical College. Joshua has special expertise developing and overseeing mass spectrometry assays in the clinical laboratory.
In the thrilling conclusion of this four part series, Josh encounters issues with his vacuum manifold, decides to forgo sample preparation, and attempts to validate a dilute-and-shoot mass spectrometry method. Problems are encountered. This session will outline the studies conducted and planned in order to complete validation of a mass spectrometry method in a CAP-accredited, clinical laboratory. While accuracy and precision and reportable range will be addressed, particular attention will be paid to the additional validation studies that should be conducted (matrix effect, injector stability, interferences, etc).
At the conclusion of this talk, participants should be able to
We are looking forward to our next FeMS Mass Spec Mixer coming up in March! Please join us on March 4th at 4pm PDT | 7pm EST | March 5th 11am AEST to hear from 3 more awesome transition-ers: Cameron Naylor, Saanghamitra Majumdar and Wout Bittremieux!
Hoda Safari Yazd University of Florida, MSACL Early Career Network
MSACL Early Career Network: Scientific Writing Workshop
Alicia Williams, PhD
Rutgers University
Alicia Williams (PhD, Rutgers University) is a teaching instructor in the Graduate Writing Program at Rutgers University, where she works with graduate students from all disciplines on articles, grant proposals, and dissertations. While her degree is in English literature, she has a background in writing mentorship and editing in Chemistry. With colleagues at Rutgers she is working on a book called Spatialization: A Graduate Writing Pedagogy.
This workshop will talk about manuscript writing, its organization, and concept communication. We will internalize several accessible guiding principles of good science writing by revising various breeds of bad examples (focusing on manuscripts in mass spectrometry).
This workshop is appropriate for anyone in the scientific community who has an interest in writing effectively. Both native English speakers and non-native English speakers are more than welcome.
High throughput screening, synthesis and enzymatic assay system: clinical relevance
R. Graham Cooks, PhD
Purdue University
R. Graham Cooks is the Henry Bohn Hass Distinguished Professor in the Department of Chemistry at Purdue University. He has served as major professor to 150 PhD students. Dr. Cooks’ was a pioneer in the conception and implementation of tandem mass spectrometry (MS/MS) and of desorption ionization, especially molecular secondary ionization mass spectrometry (SIMS). His work also includes the development of miniature portable mass spectrometers using ambient ionization and application of this combination to problems of trace chemical analysis at point-of-care. His interests in the fundamentals of ion chemistry focus on chiral analysis based on the kinetics of cluster ion fragmentation. His group also studies collisions of ions at surfaces for new methods of molecular surface tailoring and analysis, and nanomaterials preparation by soft-landing of ions and charged droplets. Dr. Cooks also launched new methods of small scale synthesis based on accelerated reactions in microdroplets and incorporated this capability into high throughput screening instrumentation based on DESI. This screening capability extends to enzyme assays. Dr. Cooks has been recognized with the Mass Spectrometry and the Analytical Chemistry awards of the American Chemical Society, the Robert Boyle Medal and the Centennial Prize of the Royal Society of Chemistry, and the Camille & Henry Dreyfus Prize in the Chemical Sciences. He is an elected fellow of the American Academy of Arts and Sciences, the Academy of Inventors and the U.S. National Academy of Sciences.
Nicolás Morato, PhD
Purdue University
Nicolás M. Morato is a postdoctoral research associate at Purdue University in Prof. R. Graham Cooks group, where he also earned his Ph.D. in 2023. He received B.Sc. degrees in chemistry (cum laude, 2017) and industrial engineering (summa cum laude, 2018) from Universidad de los Andes, Colombia. His research has focused on the development of ambient ionization methodologies for the rapid and simple analysis of complex samples, particularly oriented towards forensics and high throughput bioanalysis. His work has resulted in several honors including the Charles H. Viol Memorial Fellowship, the Eastman Summer Fellowship in Analytical Chemistry, the ACS Division of Analytical Chemistry Graduate Fellowship, the Tomas B. Hirschfeld Scholar Award, the ASMS graduate student travel award, and the Journal of Mass Spectrometry postgraduate award.
We describe an automated high throughput screening system which is used to acquire mass spectra at a rate of 6,000 samples/hour using desorption electrospray ionization (DESI). The system has been used to screen organic reactions and select optimum conditions for scaled-up drug synthesis, to analyze biological fluids without sample workup, to examine tissue library arrays and to perform label-free quantitative measurements of enzyme kinetics. Extensions of the instrumentation to collection of small amounts of synthesis products for in situ bioassays are also described.
Tamas Pongracz, PhD Leiden University Medical Center
Ettore Gilardoni University of Milan
ECN Europe: Fireside Chat with Prof. Manfred Wuhrer and Dr. Mikhail Savitski, COVID-19 and Mass Spectrometry
Manfred Wuhrer, PhD, Prof. dr.
Leiden University Medical Center
Manfred Wuhrer is Professor of Proteomics and Glycomics and head of the Center for Proteomics and Metabolomics at the Leiden University Medical Center, The Netherlands. With his research he focuses on the development of mass spectrometric methods for glycomics and glycoproteomics, and their application in clinical research and biotechnology. Clinical applications cover the fields of rheumatoid arthritis, inflammatory bowel disease, autoimmune hepatitis, diabetes, colorectal and pancreatic cancer, longevity, as well as various infectious diseases.
Mikhail Savitski, PhD
EMBL
Mikhail Savitski studied mathematics and physics at Uppsala University, where he also did his PhD in ion physics/mass spectrometry. After his PhD he worked at Cellzome as Group Leader in the Analytical Sciences department. Since 2016 he works at EMBL heading a research group as well as the proteomics core facility. He develops novel proteomics technologies and uses them to study post-translational regulation. He is an author of 87 peer reviewed publications including corresponding author papers in Nature, Cell, Science.
Mass spectrometry has demonstrated to be a powerful analytical tool for the study of SARS-CoV-2, contributing to our ability to understand and tackle the impact of COVID-19. During January and February, we will be interviewing scientists working in COVID-19 research using mass spectrometry, to learn about their projects and scientific career. Join our next COVID-19 Career Fireside chat to learn from Prof. Manfred Wuhrer and Dr. Mikhail Savitski about their COVID-19 projects, as well as their stories, lessons and advice on career paths in mass spectrometry.
Norah Alghamdi, Ph.D. University of Louisville Hospital.
Pathology Department
Getting going with mass spectrometry: Josh analyzes peaks
Joshua Hayden, PhD, DABCC, FACB
Norton Healthcare
Joshua is currently the Chief of Chemistry at NortonHealthcare. He earned his PhD in chemistry from Carnegie Mellon University. He conducted postdoctoral research at Massachusetts Institute of Technology before completing a two-year clinical chemistry fellowship at University of Washington and 4 years as Assistant Professor at Weill Medical College. Joshua has special expertise developing and overseeing mass spectrometry assays in the clinical laboratory.
Min Yu, MD, PhD, DABCC
University of Kentucky Medical Center
Dr. Min Yu is the assistant professor, associate director of clinical chemistry and the director of clinical toxicology laboratory of the Department of Pathology and Laboratory medicine at the University of Kentucky. Dr. Yu earned her medical degree at the Nanjing Medical University in Nanjing, China, where she also completed her graduate education in pharmacology (MS). Dr. Yu received her PhD degree in Molecular and Environmental Toxicology from University of Wisconsin-Madison. She completed her clinical chemistry fellowship training at the University of Virginia and then became a Diplomate of the American Board of Clinical Chemistry. Her professional area of interests includes laboratory tests harmonization and utilization, drug of abuse testing and clinical toxicology. In addition, she is actively involved in conducting clinical and translational research on evaluation of biomarkers for diagnosis and prognosis of diseases. Uniquely, she is taking advantage of the open-source computational tools (machine learning, for example) to gain new insights from the laboratory data. Her work has been published in peer- reviewed journals and has been presented to the national and international meetings.
Continuing on with mass spectrometry misadventures, this session will discuss our efforts to begin analyzing and evaluating mass spectrometry data. Unlike conventional immunoassays which provide simple (and often incorrect!) results, mass spectrometers provide a plethora of data for every peak- qualifier ions, internal standard areas, retention times, peak shapes, etc. This data, often termed metadata, can help clinical laboratories evaluate their peaks to ensure that they are reporting accurate results. Unfortunately, the process of evaluating this metadata can be a doubting challenge. This session will discover our efforts to move ahead with implementing manageable processes for evaluating the metadata necessary to ensure accurate results.
At the conclusion of this talk, participants should be able to
At the conclusion of this talk, participants should be able to
Expanding information content by integrating ion mobility spectrometry and chimeric tandem mass spectrometry in data dependent and independent workflows for the analysis small molecules in complex samples
Prof. Gérard Hopfgartner
University of Geneva
Our research integrates the role of new technologies, workflow and software for the analysis of molecules of biological interest. The overall goal is to develop innovative analytical tools and solutions that will benefit the detection and understanding of disease, and the discovery and development of appropriate therapeutics. All aspects of analytical sciences from sample collection to assay validation are considered in our research where mass spectrometric detection plays a central role. In addition to the application of separation sciences (GC, LC, SFC) combined to mass spectrometry, disruptive approaches based on MALDI or ion mobility for high throughput, multiplexed and low cost analyses of biomarkers and pharmaceuticals are investigated.
Our scientific interests include: separation sciences, sample preparation, automation, bioanalysis, metabolism, metabolomics, analytical proteomics, toxicology, high resolution mass spectrometry, ion mobility mass spectrometry, data independent acquisition techniques (SWATH), MS/MS spectra interpretation, ionization, data analysis and mass spectrometry imaging.
Development of a Covid-19 Diagnostic Test Utilizing MALDI ToF Mass Spectrometry
Elizabeth Gaillard, PhD
Northern Illinois University
The general topic of interest in our research group is the study of the mechanisms involved in photooxidative damage to biological systems, particularly in the human eye. Photooxidative damage is implicated in a number of ocular disorders such as age‐related cataract formation and age‐related macular degeneration (AMD; the leading cause of blindness in older adults). Light damage to biological systems may not manifest itself on a macroscopic level for decades, but the damage is initiated by short‐lived, electronically excited species that participate in Type I or Type II oxidative chemistry. We use a wide variety of experimental methods to study these systems, including laser‐based time‐resolved spectroscopy. By determining the sequence of events that leads to tissue injury and identifying the reactive species along the reaction pathway, we may be able to develop methods to slow down or stop these processes.
In collaboration with Prajkta Chivte and Zane LaCasse
Norah Alghamdi, Ph.D. University of Louisville Hospital.
Pathology Department
Analytical detection of drug exposure: new approaches to an old problem
Kara Lynch, PhD, DABCC
University of California San Francisco
Dr. Kara Lynch is a Professor of Laboratory Medicine at the University of California San Francisco, Co-Director of the Core Laboratory at Zuckerberg San Francisco General Hospital and Chemistry Director at UCSF Benioff Children’s Hospital Oakland. She is the co-director of the COMACC-accredited Clinical Chemistry Fellowship Program at UCSF. Her laboratory conducts studies aimed at identifying and quantifying endogenous and exogenous small molecules in biological specimens using novel diagnostic technologies, such as high resolution mass spectrometry, ion mobility mass spectrometry, ambient ionization mass spectrometry and biolayer interferometry. Her lab is involved in translational research studies evaluating the clinical utility of novel biomarkers or biomarker panels to diagnosis, treat and monitor disease. The methods developed in her laboratory are used to investigate perturbations in metabolic pathways caused by disease and drug use and translate the results into information that can be used in clinical practice.
Immunoassay urine drug screening has been the mainstay for the detection of drug exposure in patients for decades despite many limitations this approach presents. Positive samples are batched for confirmatory testing by LC-MS/MS targeted methods. Testing is limited to one matrix, a limited list of drugs/metabolites, and manual batch testing restricting interpretation, window of detection and timeliness of results to impact patient care. Utilization of alternative matrices, such as breath and oral fluid, is emerging for specific toxicological questions. Alternative analytical approaches, such as broad-spectrum drug testing with high resolution mass spectrometry, direct-to-mass spec testing with ambient ionization, and ion mobility mass spectrometry have the potential to change the landscape of drug testing in clinical laboratories. This talk will discuss alternative matrices and novel mass spectrometry-based approaches for drug detection.
Get-the-Basics: Breath Analysis Primer with Dr. Ilaria Belluomo
Ilaria Belluomo, PhD
Imperial College London
Ilaria is currently a postdoc scientist at Imperial College London. Her main research interest is the discovery and validation of volatile biomarkers in human breath using mass spectrometry, for the development of non-invasive diagnostic techniques for early cancer detection. She obtained her PhD in analytical chemistry, working between Italy and France as part of a European PhD program.
An overview of the fundamentals that are driving research and development in the field of Breath Analysis.
This is part of a series of Primers on topics relevant to Clinical Mass Spectrometry.
Learning objectives include:
1. Be able to define what Breath Analysis is, why it matters, and why you personally should care. What is the clinical relevance?
2. Understand what role mass spectrometry plays in this field. Where does mass spec fit in to the big picture of the field?
3. Define any terminology that is specific to this field.
4. Describe how it works, what are the methods and workflows used when studying this field and/or how is it implemented in clinical labs.
5. Identify any challenges to implementation/adoption, where do the opportunities lie?
"Get-the-Basics": Microbiology primer with Dr. Simon Cameron
Simon Cameron, BSc PhD
Queen's University Belfast
I currently hold an appointment at Queen’s University Belfast as a Vice-Chancellor’s Fellow (lecturer-equivalent position) where my group applies mass spectrometry and microbiology techniques to the direct-from-specimen diagnosis of pathogens and in the analysis of host-microbiome and early-life nutrition-microbiome interactions. I received my BSc (2011) and PhD (2015) from Aberystwyth University, Wales, UK in the area of molecular microbiology and metabolomics. I previously coordinated the work of the MicrobeID team within Professor Zoltan Takats’s research group at Imperial College London, which developed rapid evaporative ionisation mass spectrometry (REIMS) as a high-throughput platform to assign taxonomic and functional classifications to microbial isolates and to the direct-from-sample profiling of mixed microbial communities.
An overview of the fundamentals that are driving research and development in the field of Microbiology.
This is part of a series of Primers on topics relevant to Clinical Mass Spectrometry.
Learning objectives include:
1. Be able to define what Microbiology is, why it matters, and why you personally should care. What is the clinical relevance?
2. Understand what role mass spectrometry plays in this field. Where does mass spec fit in to the big picture of the field?
3. Define any terminology that is specific to this field.
4. Describe how it works, what are the methods and workflows used when studying this field and/or how is it implemented in clinical labs.
5. Identify any challenges to implementation/adoption, where do the opportunities lie?
Ethan Yang, PhD Johns Hopkins University, MSACL Early Career Network
Mudita Vats Maastricht University
ECN Asia-Pacific: Fireside Chat with Dr. Gus Grey and Mr. Mark De Hora
Gus Grey, PhD
University of Auckland
Dr Gus Grey is a senior research fellow in the Department of Physiology, University of Auckland, academic director of the Biomedical Imaging Research Unit and principal coordinator of the University’s Mass Spectrometry Hub. He completed his PhD in Auckland before pursuing post-doctoral research in the United States. While in the US he learnt MALDI imaging mass spectrometry at MUSC and Vanderbilt University. He returned to New Zealand at the end of 2009 and acquired MALDI imaging equipment which he now utilises in his own research. His lab aims to use this spatially-resolved technique to understand the basis of ocular lens tissue transparency, the biomolecular changes that take place in cataract formation, and use this knowledge to develop novel therapies to delay or prevent the onset of lens cataract. He also collaborates locally with other researchers to apply MALDI imaging to further understand the pathological processes involved in neurodegeneration, cancer, and even fruit development.
Mark De Hora, MSc. MA FIBMS FFSc.(RCPA)
Auckland City Hospital
Mark De Hora graduated from the National University of Ireland, Galway with a degree in Science in 1987. He began his career as a Biomedical Scientist in London in 1988 and worked in 4 different London Hospitals. He completed his MSc in Clinical Biochemistry in 1997 when he had his first exposure to GCMS. He began working in the West of England Newborn Screening and Biochemical Genetics laboratory in 2003 specialising in GCMS and LCMSMS investigations for inherited metabolic diseases. He moved to Auckland in 2011 with his family and works for the National Newborn Screening and Biochemical Genetics laboratory at the Starship Hospital in Auckland. Mark has completed the Fellowship of the Royal College of Pathologists Faculty of Science in 2016 and is currently enrolled for PhD programme looking at expanded steroid profiling in bloodspots using high resolution mass spectrometry.
Learn about biomedical imaging Mass spectrometry going on in academia from Dr. Gus Grey and dive deeper into clinical applications of MS with Mr. Mark De Hora in Auckland, New Zealand.
Note this session Date and Time:
Auckland - Jan 26, 4:00pm
Melbourne - Jan 26, 2:00pm
Beijing - Jan 26, 11:00am
Mumbai - Jan 26, 8:30am
Is there a Medical and Toxicology Role for Cannabis Testing in the Clinical Laboratory?
Jack Henion, PhD
Henion Enterprises
Professor Jack Henion is Emeritus Professor of Toxicology at Cornell University where he was a member of the College of Veterinary Medicine commencing in 1976. Dr. Henion was co-founder of Advion BioSciences in 1993 where he served as President and CEO until 2006 when be became CSO of Advion, Inc. Dr. Henion carried out a wide range of research in many application areas involving GC/MS and LC/MS/MS techniques. Professor Henion has received three Doctor Honoris Causa (Honorary Doctorate) degrees in recognition of his international reputation in modern analytical techniques. These were awarded from each of the University of Ghent, Uppsala University and Albany University. During his tenure at Cornell Professor Henion conducted research and explored applications in many areas of liquid chromatography/mass spectrometry (LC/MS) employing atmospheric pressure ionization (API) sources. Professor Henion has published over 235 peer reviewed papers in the scientific literature, trained nearly 100 students, post-doctoral scientists, and trainees while receiving 12 patents for inventions developed from his work. He has also received a number of awards which recognize his contributions to analytical chemistry and entrepreneurship. More recently in April 2017 Dr. Henion received the Outstanding Contribution to Anti-Doping Science Award from the Partnership for Clean Competition (PCC) for his development of a novel Book-Type Dried Plasma Spot Card and in the Fall of 2017 Dr. Henion was the winner of the 2018 Bioanalysis Outstanding Contribution Award (BOSCA). In December 2019 Dr. Henion retired from Advion, Inc. and is now a consultant for Henion Enterprises.
The use of cannabis and cannabis-derived products by both young and older patients continues to increase. The COVID pandemic has forced people to remain home and be socially distance such that loneliness has increased both the use of alcohol as well as cannabis. A recent news report indicated cannabis sales has increased nearly 25% because of COVID-induced stress and social loneliness. The recent election added four additional states to those allowing legal use of recreational cannabis. There are also many anecdotal reports on the effectiveness of CBD and associated cannabis-derived products which has attracted a passionate following of those who believe using these products helps their ailments.
With these trends it should not be surprising that an increasing number of patients have cannabis-derived chemicals in their body fluids. Although patient ailments may or may not be attributed to cannabis compounds and their metabolites, the
Fireside chat with Prof. Andrea Sinz, COVID-19 and Clinical mass spectrometry
Andrea Sinz, PhD
Martin-Luther-University Halle-Wittenberg
Prof. Andrea Sinz is a member of the COVID-19 Mass Spectrometry coalition and she has been working on mass spectrometric Identification of SARS-CoV-2 Proteins from gargle solution samples of COVID-19 patients (Ihling C, Tänzler D, Hagemann S, Kehlen A, Hüttelmaier S, Arlt C, Sinz A. J Proteome Res. 2020; 19:4389-93). She is a full Professor of Pharmaceutical Chemistry at the Martin-Luther-University Halle-Wittenberg in Germany. The focus of her laboratory is the development of novel tools and workflows to promote the crosslinking/mass spectrometry (XL-MS) approach. She obtained her PhD in Pharmaceutical Chemistry from the University of Marburg, Germany. She received a degree in Pharmacy from the University of Tübingen, Germany. She was a post-doctoral fellow at the National Institutes of Health in Bethesda, MD, USA, where she became introduced into chemical cross-linking techniques and protein mass spectrometry. From 2017 to 2020, she was the president of the German Society for Mass Spectrometry and in 2016 she was recognised as one of the top 50 most influential women in Analytical Science.
Mass spectrometry has demonstrated to be a powerful analytical tool for the study of SARS-CoV-2, contributing to our ability to understand and tackle the impact of COVID-19. During January and February, we will be interviewing scientists working in COVID-19 research using mass spectrometry, to learn about their projects and scientific career. Join our first COVID-19 Career Fireside chat to learn from Prof. Andrea Sinz about her COVID-19 project, the COVID-19 MS coalition, as well as her stories, lessons and advice on career paths in clinical mass spectrometry.
Supported by an Open Unrestricted Educational Grant
provided by
There is no cost to register for this activity.
Clinical Proteomics: Catching Flies with Chopsticks
Andy Hoofnagle, MD, PhD
University of Washington
Dr. Hoofnagle's laboratory focuses on the precise quantification of recognized protein biomarkers in human plasma using LC-MRM/MS. In addition, they have worked to develop novel assays for the quantification of small molecules in clinical and research settings. His laboratory also studies the role that the systemic inflammation plays in the pathophysiology of obesity, diabetes, and cardiovascular disease.
As a field, we have made great strides in quantifying proteins with LC-MS/MS. There has always been great hope that these advances will lead to the improved care of patients and there are now tangible examples. Our laboratory has had the honor of collaborating with laboratories around the world with the aim of getting it right. This presentation will highlight a few of those collaborations, touch on related efforts from other groups, and outline where we are headed next.
From Beer to Bacteria and Beyond: Towards Chemical Multi-Fingerprinting
Kevin Schug, PhD
University of Texas Arlington
Kevin A. Schug is Professor and the Shimadzu Distinguished Professor of Analytical Chemistry in the Department of Chemistry and Biochemistry at The University of Texas at Arlington (UTA). He is also Director of the Collaborative Laboratories for Environmental Analysis and Remediation (CLEAR) at UTA. He received his B.S. degree in Chemistry in 1998 from the College of William and Mary, and his Ph.D. degree in Chemistry from Virginia Tech in 2002 under the direction of Prof. Harold M. McNair. From 2003-2005, he performed post-doctoral research at the University of Vienna in Austria with Prof. Dr. Wolfgang Lindner. Since joining UTA in 2005, his research has been focused on the theory and application of separation science and mass spectrometry for solving a variety of analytical and physical chemistry problems, in the fields of environmental, pharmaceutical, biological, and energy research. He has over 180 peer-reviewed publications and over 400 presentations, posters, and invited talks to his group’s credit. He has been the primary mentor and research advisor to more than 30 graduate and 60 undergraduate students. Dr. Schug has received several research awards, including the 2009 Emerging Leader Award in Chromatography by LCGC Magazine and the 2013 American Chemical Society Division of Analytical Chemistry Young Investigator in Separation Science Award. Recently, he was named to 2019 The Analytical Scientist’s Top 100 Power List of the best analytical chemists in the world. For his teaching, he received the 2014 University of Texas System Regents’ Outstanding Teaching Award and in 2017, was awarded the J. Calvin Giddings Award for Excellence in Analytical Chemistry Education by the American Chemical Society. He is a Fellow of both the University Of Texas System’s and U.T. Arlington’s Academy Of Distinguished Teachers.
A wide array of analytical instrumentation exist to perform quantitative and qualitative analysis on complex mixtures. The choice of chemical analysis tool, in conjunction with appropriate sample preparation, allows the lens to be focused on a particular sample dimension. Loosely, different sample dimensions can be equated to different classes of analytes contained in a sample. While, we ultimately will likely use very different strategies to characterize e.g. fatty acids vs. proteins in a biological sample, there is potentially value in monitoring each of these analyte classes for correlations with physiological changes that may results as part of a disease or some other abnormality. In fact, if one were trying to classify samples that were normal vs. abnormal, it could be argued that, while the monitoring of one sample dimension might be more diagnostic than another, monitoring and combining data from multiple sample dimensions would like provide additional information to aid the classification. This concept of chemical multi-fingerprinting (CMF) could ultimately help draw lines between different sample classifications, where they were previously difficult to discern. We are currently working to define useful strategies for the combination of multiple analytical techniques for CMF of various sample types. This includes the development of highly featured targeted and non-targeted methods using:
Headspace
Getting going with mass spectrometry: Josh learns chromatography
Joshua Hayden, PhD, DABCC, FACB
Norton Healthcare
Joshua is currently the Chief of Chemistry at NortonHealthcare. He earned his PhD in chemistry from Carnegie Mellon University. He conducted postdoctoral research at Massachusetts Institute of Technology before completing a two-year clinical chemistry fellowship at University of Washington and 4 years as Assistant Professor at Weill Medical College. Joshua has special expertise developing and overseeing mass spectrometry assays in the clinical laboratory.
Susan Abbatiello, PhD
Northeastern University
Susan Abbatiello earned a B.A. in Chemistry at The College of the Holy Cross. She worked for 5 years at Genetics Institute (Andover, MA) in the Biopharmaceutical Characterization and Analysis group before returning to graduate school. Susan earned her Ph.D. in Analytical Chemistry at the University of Florida, working under advisement of Drs. John Eyler and Nigel G. J. Richards, focusing on the quantitation of a protein suspected to play a role in drug-resistant acute lymphoblastic leukemia. Susan worked as a post-doc in the Clinical Proteomics facility at the University of Pittsburgh for Dr. Thomas P. Conrads, where she continued efforts in targeted proteomics research with a focus on cancer. In 2008, Susan moved to the role of Scientist in the Proteomics Platform at the Broad Institute (Dr. Steven Carr), where she served as co-chair of the NCI CPTAC (National Cancer Institute Clinical Proteomics Technology Assessment for Cancer) working group to evaluate stable isotope dilution selected reaction monitoring for the quantitation of plasma proteins related to cancer. In 2014, Susan transitioned to the role of Triple Quadrupole Product Specialist at Thermo Fisher Scientific and took on the responsibilities of FAIMS Product Manager in 2015. In 2018, Susan transitioned to the role of Executive Director of the Barnett Institute for Chemical and Biological Analysis, overseeing the Mass Spectrometry Core Lab. In 2020, she accepted the position of Interim Director of the Barnett Institute, while continuing the MS Core Lab responsibilities.
Susan’s research interests include evaluation and making improvements in technologies for the targeted analysis and detection of biomarker candidates in blood, tissue, and cell samples. Her efforts have focused on improving accessibility and performance of mass spectrometric technologies and software, to help broaden its impact in basic, biomedical, and analytical research. Her work has resulted in over one dozen peer-reviewed publications as well as invited presentations at national conferences.
Susan has been a member of ASMS since 2002. She has participated in poster abstract evaluation and has organized and chaired oral sessions and served on the program committee for ASMS Conferences. Susan has been a short-course instructor for the ASMS short course “Practical LC-MS Troubleshooting and Maintenance” since 2013. She served as the Vice President of Arrangements for ASMS from 2017-2019. Susan is also a member of ACS, is a reviewer for Analytical Chemistry, Journal of Proteome Research, Nature, and is currently on the Editorial Board of Molecular & Cellular Proteomics.
On a personal note, Susan has been married to Russell Abbatiello for 23 years and they have a 10 year old daughter, Madeline, and a 7 year old son, James. They enjoy dressing up for Halloween as a family affair, and have attempted to replicate characters from Frozen, The Incredibles, Toy Story 4, and Despicable Me.
What do we want? Good chromatography! How do we get it? We don
Learning Objectives:
1. Define what good chromatography means for an LC-MS/MS method
2. State the situations where reverse phase or HILIC columns might be most appropriate
3. Explain the significance of various column factors (chemistry, length, particle size, etc)
4. Explain the value of mobile phase additives (formic acid, ammonium formate, etc)
Mass spectrometry & informatics to the rescue: therapeutic drug monitoring of infliximab
Grace van der Gugten, B.Sc. Chemistry
Alberta Precision Laboratories
Grace discovered her love for clinical mass spectrometry when she began working at St Paul's Hospital in Vancouver in the special chemistry mass spec group with Dr. Dan Holmes in late 2010. Grace was challenged in this role but gained a wealth of knowledge and experience over her 10+ years in the SPH laboratory. She puts this experience and knowledge into use in her current role as Lab Scientist in the Newborn Screening and Biochemical Genetics lab at Alberta Precision Laboratories in Edmonton. Grace loves developing streamlined, easy to use (if possible!) clinical mass spectrometry assays; teaching others and helping others succeed; and troubleshooting (especially when the problem is solved!).
Mari DeMarco, PhD, DABCC, FACB, FCACB
University of British Columbia
Mari DeMarco, PhD, DABCC, FCACB, is a Clinical Chemist at Providence Health Care, the Research Director of Providence Research, and a Clinical Associate Professor in Pathology and Laboratory Medicine at the University of British Columbia in Vancouver Canada. Dr. DeMarco completed her PhD in the Biomolecular Structure and Design program at the University of Washington, and a clinical chemistry fellowship at Washington University School of Medicine.
With a strong interest in bridging basic biomedical science, analytical chemistry and laboratory medicine, Dr. DeMarco’s research group focuses on building new biofluid tests for direct translation into patient care. A particular area of interest is advancing protein-based clinical diagnostics for neurodegenerative disorders, such as Alzheimer’s disease. The goal of this program of research is to ensure that these new tools make the challenging jump from research into healthcare.
Stephen Master, MD, PhD, FADLM
Children's Hospital of Philadelphia
Stephen Master received his undergraduate degree in Molecular Biology from Princeton University, and subsequently obtained his MD and PhD from the University of Pennsylvania School of Medicine. After residency in Clinical Pathology at Penn, he stayed on as a faculty member with a research focus in mass spectrometry-based proteomics as well as extensive course development experience in bioinformatics. After time as an Associate Professor of Pathology and Laboratory Medicine at Weill Cornell Medicine in New York City, where he served as Director of the Central Lab and Chief of Clinical Chemistry Laboratory Services, he took a position at the Children's Hospital of Philadelphia at Chief of Lab Medicine. One of his current interests is in the applications of bioinformatics and machine learning for the development of clinical laboratory assays. He would play with R for fun even if he weren't getting paid, but he would appreciate it if you didn't tell that to his department chair.
Infliximab (IFX) is an anti-TNF monoclonal antibody therapy used to treat autoimmune disorders such as Crohn
References:
1. Trasolini R and DeMarco ML. ‘Therapeutic drug monitoring of monoclonal antibody infliximab’ ASCP Case Reports, October, 2016.
2. Robert A. Mitchell, Constantin Shuster, Neal Shahidi, et al., ‘The Utility of Infliximab Therapeutic Drug Monitoring among Patients with Inflammatory Bowel Disease and Concerns for Loss of Response: A Retrospective Analysis of a Real-World Experience,’ Canadian Journal of Gastroenterology and Hepatology, vol. 2016, Article ID 5203898, 7 pages, 2016. doi:10.1155/2016/5203898
3. Niels Vande Casteele, Marc Ferrante, Gert Van Assche, et al., ‘Detection of infliximab levels and anti-infliximab antibodies: A comparison of three different assays’ Aliment Pharmacol. Ther 2012; 36:765-771
4. Bader, LI, Sol Solbert, SM, Kaada SH., et al., ‘Assays for Infliximab Drug Levels and Antibodies: A Matter of Scales and Categories’ Scand J Immunol 2017; 86:165-170
Prof. Hewison is currently Professor of Molecular Endocrinology within the Institute of Metabolism and Systems Research (IMSR) at the University of Birmingham, UK, having worked from 2005 – 2014 at the University of California Los Angeles. Prof. Hewison’s main research interest is vitamin D and its importance to human health. He has published over 230 research papers on classical (skeletal) and non-classical (extra-skeletal) actions of vitamin D. Prof. Hewison’s group is at the forefront of research linking vitamin D and the immune system, with implications for a wide range of clinical disorders including infectious, inflammatory and autoimmune disease. Current studies are focused on the analysis of vitamin D-insensitivity in T lymphocytes from the inflamed joints of patients with rheumatoid arthritis. This may provide an explanation for the limited success of vitamin D supplementation in some clinical trials. Other projects have explored the role of cell metabolism pathways in mediating the immunomodulatory effects of vitamin D, and the opportunities this may provide for improved therapeutic use of vitamin D. The Hewison group has also pioneered a range of studies to explore alternative markers of vitamin D ‘status’. This includes development of novel high throughput liquid chromatography-tandem mass spectrometry technology to measure multiple metabolites of vitamin D – the vitamin D metabolome – and analysis of the role of the serum vitamin D binding protein as a determinant of vitamin D bioavailability within the immune system. Prof. Hewison is a recipient of a Royal Society Wolfson Fellowship. His research is supported by grants from the Medical Research Council and Biotechnology and Biological Sciences Research Council (UK), and the National Institutes of Health (USA).
Imaging 101 : Clinical Studies using Imaging Mass Spectrometry
Sankha (Bobby) Basu, MD, PhD
Brigham and Women’s Hospital
Sankha (Bobby) Basu, MD, PhD received his BS in Biology and Chemical Engineering in 2003 at MIT and obtained his MD and PhD (Pharmacology) degrees in 2013 from the University of Pennsylvania School of Medicine. His thesis work involved the development and application of stable isotope LC-MS/MS methods to study mitochondrial disease, which was conducted in the laboratory of Dr. Ian Blair. He then went back to Boston to complete a residency in Clinical Pathology and a fellowship in Medical Microbiology at the Brigham and Women's Hospital (BWH). Following his clinical training, he joined the laboratory of Dr. Nathalie Agar at BWH as a post-doctoral research fellow working on a variety of applications including intraoperative MS and MALDI MSI. He recently joined the faculty at BWH as Assistant Director of Clinical Chemistry and Mass Spectrometry and Instructor of Pathology at Harvard Medical School. His clinical roles include the development and implementation of LC-MS methods in clinical chemistry and MALDI TOF based microbial identification in microbiology. Additionally, he continues his work with the Agar lab on clinical and translational applications of MS.
Christina Ferreira, PhD
Purdue Metabolite Profiling Facility at Bindley Bioscience Center
Christina R. Ferreira works as Lipidomics Scientist in the Metabolite Profiling Facility at Purdue University. Her main research interest is the application of the MRM-profiling method for the exploratory analysis of lipids and metabolites in developmental biology models. At Prof. Cooks lab, she created the MRM-profiling method and contributes to diverse projects from the Cooks lab related to further developing this method. Dr. Ferreira also supports the application MRM-profiling in research projects served by the multi-user Purdue Metabolite Profiling Facility at Bindley Bioscience Center. She is also the project manager for a large effort (Purdue Make-It System) for high-throughput screening and analysis of chemical reactions using DESI-MS.
Michelle Reyzer, PhD
Vanderbilt
Michelle Reyzer received her BS in Chemistry from the College of William and Mary in Virginia in 1991, and after that worked at the NIH at the National Institute for Alcohol Abuse and Alcoholism (NIAAA) in the Laboratory of Membrane Biochemistry and Biophysics for 5 years. She then went to the University of Texas at Austin where she received a PhD in Analytical Chemistry in 2000 in the laboratory of Jennifer Brodbelt. The was followed by a post-doctoral fellowship at Vanderbilt in the laboratory of Richard Caprioli where she was introduced to MALDI Imaging Mass Spectrometry. She has been focused on the use of MALDI for imaging biological tissues for the past 14 years. Michelle is currently a Research Assistant Professor at Vanderbilt University Medical Center, and also serves as the Associate Director of the Tissue Imaging Core laboratory, where she routinely develops methods for the analysis of small molecules in tissue sections for investigators within Vanderbilt as well as external collaborators. In addition, Michelle oversees the collaboration and service projects for the National Research Resource for Imaging Mass Spectrometry.
This is a 2-Day Course with 7 total contact hours.
Overview: Over the past two decades we have seen considerable scientific and technological advancements in imaging mass spectrometry (IMS), as these approaches continue to be implemented in research and industry. There has, however, been limited adoption of these techniques into the clinical arena, in part due to gaps between the mass spectrometrists developing these tools, and the clinical stakeholders, such as surgeons and pathologists, who may one day use them in their practices.
The goal of this course is to bridge these gaps by (1) providing an overview of the principles, strengths, limitations and applications of IMS techniques, such as MALDI-IMS and ambient mass spectrometry (AMS), and (2) offering insight into clinical workflows and potential opportunities for applications. The target audiences include both clinicians, surgeons, and pathologists interested in learning more about IMS applications as well as mass spectrometrists interested in clinical applications of IMS. The first day will focus on MALDI IMS, while the second day will cover ambient MS.
Thursday
7:00 - 8:10am
Clinical tissue analysis: overview of workflows and diagnostic "blind spots" (BB) (70 min)
8:20 - 9:30am
Introduction to MALDI IMS (MR) (70 min)
9:40-10:50am
Advancements and applications using MALDI IMS (MR) (70 min)
Friday
7:00 - 8:10am
Introduction to ambient MS (CF) (70 min)
8:20 - 9:30am
Advancements and applications using AMS (CF) (70 min)
9:40-10:50am
Bringing IMS into the clinic: opportunities and challenges (BB) (70 min)
Ólöf Gerður Ísberg, MSc, PhD Vanderbilt University, MSACL Early Career Network
ECN: Interview Skills Workshop with Career Focus on Proteomics
Matthias Trost, PhD
Newcastle University, UK
Matthias is a proteomics expert with over 20 years of experience in mass spectrometry. He studied Chemistry in Freiburg, Germany, and Manchester, UK, did his PhD in Cellular Microbiology and Proteomics at the Helmholtz-Centre for Infection Research in Braunschweig, Germany and his post doctoral research at the Institute for Research in Immunology and Cancer in Montréal, Canada. In 2010, Matthias became Group Leader and Head of Proteomics at the MRC Protein Phosphorylation and Ubiquitylation Unit (MRC PPU) at the University of Dundee. In 2017, Matthias was appointed Professor of Proteomics at Newcastle University. Since 2019, he is a Wellcome Trust Investigator. His main biological interest is in phagosome and macrophage biology and particularly signalling events in innate immunity driven by phosphorylation and ubiquitylation. In recent years, his lab has additionally focused on using mass spectrometry for drug discovery. For this, the lab pioneered the usage of high-throughput MALDI TOF mass spectrometry for drug screening which has attracted significant industry interest.
Lisa Jones, PhD
University of Maryland
Lisa M. Jones is an Associate Professor in the Department of Pharmaceutical Sciences at the University of Maryland. She received her BS from the Department of Chemistry at Syracuse University and her PhD in Chemistry from Georgia State University. She received postdoctoral training in structural virology at the University of Alabama- Birmingham and in MS-based protein footprinting at Washington University in St. Louis. Dr. Jones’s research interests include the use of the protein footprinting method fast photochemical oxidation of proteins (FPOP) coupled with mass spectrometry for the characterization of the higher order structure of proteins. In particular, her lab has further developed the FPOP method for in-cell (IC-FPOP) studies for proteome-wide structural biology. Biological applications of IC-FPOP include characterizing protein folding intermediates directly in the cell and drug target (both on and off targets) determination. The Jones lab has also extended the method for in vivo analysis (IV-FPOP) in C. elegans. This provides the ability to study protein structure in an animal model for human disease.
Looking for an opportunity to hone your interview skills? This is the place for those looking to transition in entry-level positions. Two interviewees will present their elevator pitch and respond to a series of interview questions from a panel of experts and/or hiring managers in a particular field. After their mock interview, the panelists will provide their feedback. This month
New Mass Spectrometer Technology to Advance Biomedical Research
Joshua Coon, PhD
National Center for Quantitative Biology of Complex System, University of Wisconsin-Madison
I grew up in rural Michigan and during these formative years greatly enjoyed flyfishing and woodworking. Putting the latter interest to practical use, I constructed several riverboats (for fishing) while in high school and college. Chemistry interested me, especially Analytical Chemistry, as it offered an avenue to continue “building”. Not boats, but chemical instrumentation. To escape the cold I joined the Chemistry graduate program at the University of Florida and worked with Willard Harrison. Professor Harrison didn’t just guide my research, he taught me how to write, present, and think like a scientist. He was a gentleman in every sense of the word. Upon graduation in 2002, I moved to Charlottesville, Virginia to join the laboratory of Professor Don Hunt. At Virginia I met John Syka. Don and John both shared a passion for science that was as infectious as it was inspiring. Together we worked to develop electron transfer dissociation (ETD). ETD worked just as we had hoped and the dissociation technique is now commonly used for proteomics and has been commercially introduced by no fewer than four major instrument vendors. In 2005 I moved to Wisconsin to start my own program. And though we have been productive and impactful with ~ 200 published manuscripts, I am most proud to have produced nearly 20 Ph.D. scientists, and our academic family continues to grow.
The sequencing of the human genome marked the beginning of a collective scientific expedition to understand complex organisms. Genes, of course, merely contain the instructions for which proteins will populate the cell. Untangling the multi-faceted networks that regulate complex organisms and their diseases will require innovative technologies to globally monitor many classes of biomolecules, including nucleic acids, proteins, and metabolites. High-throughput technologies for gene and transcript measurement are well-developed and broadly accessible, and, as such, have had a fantastic and transformative impact on modern biology and medicine. For numerous reasons, methods for global analysis of proteins and metabolites – crucial biological effector molecules – are less evolved and markedly less accessible. The overarching mission of my program is to (1) facilitate expedient, comprehensive analysis of proteins and metabolites by innovating new mass spectrometric technologies and (2) apply these techniques to advance biomedical research.
In this presentation I will describe numerous projects related to the development and application of high-throughput quantitative multi-omics. Examples include new proteomic methods and technologies to permit the deepest analysis of the human proteome to date and the discovery of thousands of alternatively spliced proteins and protein isoforms resulting from single nucleotide polymorphisms. In another example we use high throughput multi-omics to map the proteomes, lipidomes, and metabolomes of nearly 1,000 single gene knockout cell lines for large-scale functional mapping of genes. Finally, we use these same quantitative multi-omic technologies to study the molecular changes that occur during Covid-19 infection in a human cohort.
Using High Resolution Mass Spectrometry to Evaluate Trends in Fentanyl Analogues Prevalence and Other False Positives in Emergency Medicine Patients
Adina Badea, PhD, DABCC
Lifespan/Rhode Island Hospital & the Warren Alpert Medical School of Brown University
Dr. Adina Badea, PhD, DABCC, earned her BA in Chemistry from Wellesley College, and her PhD in Chemistry from the University of Illinois at Urbana-Champaign. She completed her clinical chemistry and toxicology fellowship at UCSF, where she worked under the supervision of Dr. Alan Wu and Dr. Kara Lynch on developing methods and finding new solutions to current challenges in clinical toxicology testing. Currently, she is Director of Toxicology at Rhode Island Hospital and Assistant Professor of Pathology and Laboratory Medicine at The Warren Alpert Medical School of Brown University, where she focuses on expanding the capabilities of the clinical toxicology lab using high resolution mass spectrometry. Her research interests include bringing state-of-the-art testing to the service of emergency medicine patients and to address public health crises with real-time comprehensive toxicology testing via collaborations with the local Poison Control Center and Department of Health.
# Originally scheduled for MSACL2020 US in the Scientific Session : Fentanyl at the Forefront : Using Non-traditional Approaches to Identify Fentanyl Analogs
Introduction
Deaths due to opioid overdoses have been on the rise in the United States, with a particular spike in this trend caused by the emergence of synthetic opioids including fentanyl and analogues. There have been numerous reported cases of synthetic opioids as adulterants in heroin, methamphetamine, cocaine, and counterfeit pills. As a result, they are often times consumed unknowingly, causing mixed toxidromes and confounding diagnosis. Proper routine drug monitoring is essential in addressing the ever-expanding magnitude of the opioid epidemic.
Objectives
The primary objective of this study was to observe prevalence of fentanyl analogs and other false positives in positive fentanyl screens of emergency medicine populations in order to evaluate trends in the dynamic landscape of substance abuse.
Methods
Analysis of remnant clinical samples was approved by the UCSF Institutional Review Board. Urine samples from emergency department (ED) patients with drugs-of-abuse screens performed were monitored from October 2018 to March 2019 for presence of fentanyl (via immunoassay). Samples with a positive fentanyl screen were collected and further characterized by high resolution mass spectrometry (LC-HRMS). Urine samples were diluted 1:5. Chromatography was performed using a Kinetex C18 column with a 10-minute gradient from 2%-100% organic. Data was collected on a SCIEX TripleTOF
Ethan Yang, PhD Johns Hopkins University, MSACL Early Career Network
Atiye Ahmadi, PhD University of Florida
ECN: Fireside Chat with Dr. Robert Everley and Dr. Christopher Rose
Robert Everly, PhD
Pfizer
Robert received his PhD in Analytical Chemistry from Virginia Commonwealth University applying top-down proteomics to characterize bacteria in the laboratory of Timothy Croley. Robert then transitioned to Boston Children’s Hospital as a postdoctoral fellow investigating multi-site phosphorylation dynamics using bottom-up and top-down proteomics under Hanno Steen. Next Robert pursued additional postdoctoral work in the laboratory of Steven Gygi in the Department of Cell Biology at Harvard Medical School (HMS) focusing on multiplexed proteomic strategies for phosphotyrosine signaling, selenocysteine containing protein networks and targeted proteomics. While in the Gygi Lab, Robert was a co-inventor of TOMAHAQ, a multiplexed targeted proteomics workflow. Robert then became the Director of Proteomics for the Laboratory of Systems Pharmacology (LSP) and joined the faculty at HMS at the rank of instructor. While at the LSP, Robert’s lab applied proteomics to numerous aspects of pharmacology including recently published work on covalent kinase inhibitors. Robert now leads the proteomics group within Hit Discovery & Optimization at Pfizer, where his group supports discovery programs in phenotypic screening, chemically-induced degradation, and the Centers for Therapeutic Innovation.
Christopher Rose, PhD
Genentech
Chris received his PhD in Analytical Chemistry from the University of Wisconsin Madison where he developed novel quantitative proteomics approaches in the lab of Joshua Coon. Chris continued his post-doctoral studies in the lab of Steve Gygi at Harvard Medical School where he co-developed TOMAHAQ - a targeted mass spectrometry method that combines sample and peptide multiplexing - and developed the proof-of-principle implementation of real-time search for isobaric label based quantitation. Following his post-doc, Chris joined the Microchemistry, Proteomics & Lipidomics department at Genentech where his group develops and applies leading edge quantitative proteomics methods to explore biological pathways related to potential therapeutic targets. Chris' group also focuses on analysis of low-level proteomes with a special focus on understanding technical challenges of current approaches to single cell proteomics and proposing new methods to analyze such samples.
The pharmaceutical industry is an important sector where analytical chemists, particularly mass spectrometrists, are in growing demand. What positions are available for new graduates? Join our Fireside Chat with Dr. Robert Everley and Dr. Christopher Rose to learn about a career in pharma. This session will be interactive and offers opportunities to network.
GP73 : A Glycoproteomic Story of Success and Failure
Anand Mehta, D.Phil.
Medical University of South Carolina
Anand Mehta, D.Phil., is the SmartState Endowed Chair in Proteomic Biomarkers and Professor, Department of Cell and Molecular Pharmacology at the Medical University of South Carolina. Dr. Mehta’s laboratory is focused on understanding and developing diagnostic methods and treatments for hepatocellular carcinoma (HCC). HCC is a primary cancer of the liver and kills close to 1 million people every year. The Mehta lab was one of the first to perform total serum glycan analysis for biomarker detection and one of the first to perform serum glycoproteomics. His laboratory remains on the forefront in the development of tools for the analysis of complex carbohydrates and the discovery and validation of biomarkers of HCC.
I will talk about how our first biomarker discovery was made and failed to be commercialized by us - but was commercialized by others.
Supported by an Open Unrestricted Educational Grant
provided by
Marijuana, Mass Spectrometry and the Man
Robert Fitzgerald, PhD, DABCC
University of California San Diego
Robert L. Fitzgerald, PhD, DABCC Dr. Fitzgerald received his BS degree in Chemistry at Loyola College of Maryland, and his PhD in Pharmacology/Toxicology at the Medical College of Virginia/Virginia Commonwealth University. After two and a half years as a forensic toxicologist for the State of Virginia, he took a position as the Director of the Mass Spectrometry Laboratory at the San Diego VA Hospital. Currently, Dr. Fitzgerald is a Professor in the Department of Pathology at the University of California, San Diego where he is the director of the toxicology laboratory and associate director of the clinical chemistry laboratory. He is board certified in toxicology and clinical chemistry by the American Board of Clinical Chemistry. He is the director of the clinical chemistry fellowship at UCSD.
Marijuana is increasingly being used for both medical and recreational purposes. In the US, medical use of marijuana is legal in 33 states while recreational marijuana is available in 11 states. With more widespread use, there is growing concern about the effect of marijuana on driving performance.
The University of California-San Diego (UCSD) Center for Medical Cannabis Research (CMCR) recently completed a placebo controlled, double blinded study on the effects of smoked marijuana and driving performance. 200 subjects were randomized to smoking a joint containing placebo, 5.9% or 13.4% THC. Oral fluid, breath, and whole blood samples were collected along with driving performance on a simulator. THC and nine metabolites were measured using isotope dilution tandem mass spectrometry and the sensitivity and specificity of these compounds were examined using cutoffs commonly used by some state
Supported by an Open Unrestricted Educational Grant
provided by
There is no cost to register for this activity.
Getting going with mass spectrometry: Josh installs a mass spectrometer
Joshua Hayden, PhD, DABCC, FACB
Norton Healthcare
Joshua is currently the Chief of Chemistry at NortonHealthcare. He earned his PhD in chemistry from Carnegie Mellon University. He conducted postdoctoral research at Massachusetts Institute of Technology before completing a two-year clinical chemistry fellowship at University of Washington and 4 years as Assistant Professor at Weill Medical College. Joshua has special expertise developing and overseeing mass spectrometry assays in the clinical laboratory.
The applications of mass spectrometry in the clinical laboratory continue to expand.
Unfortunately, not all clinical laboratories have mass spectrometers and there are substantial barriers to bringing in this instrumentation. This webinar will discuss some of these barriers and how we have been able to overcome them in our path towards setting up clinical mass spectrometry testing.
This session will serve as an introduction to a 4 part series in which Dr. Hayden will invite attendees to witness in real time his journey bringing mass spec testing to a clinical lab. During these interactive sessions, attendees will be encouraged to help troubleshoot, and offer advice as desired.
Subsequent sessions anticipated include:
1. Getting going with mass spectrometry: Josh learns chromatography
2. Getting going with mass spectrometry: Josh tries to do sample preparation
3. Getting going with mass spectrometry: Josh analyzes peaks
BONUS FUN ACTIVITY:
We are certain there is a very catchy title for this series. "The Real World: Clinical Mass Spec" and "Josh vs The World" didn't make the cut. If you think you have the perfect titles, let us know (Twitter handle @MSACL). Your ideas could be featured right here on MSACL Connect!
Ólöf Gerður Ísberg, MSc, PhD Vanderbilt University, MSACL Early Career Network
ECN: Interview Skills Workshop with Career Focus on Lipidomics/Metabolomics
Ruth Andrew, PhD
University of Edinburgh
Ruth Andrew holds a Chair in Pharmaceutical Endocrinology at the University of Edinburgh and directs the Clinical Research Facility Mass Spectrometry Core. After qualifying as a pharmacist in 1990, she studied for a PhD in the field of pharmaceutical analysis, using gas chromatography mass spectrometry as an approach to profile catecholamines in hypertension. In 1994, she joined the Endocrinology Unit in the University of Edinburgh to develop further interests in mass spectrometry and establish its use in steroid profiling in cardiovascular disease. Since then Ruth has investigated the regulation of glucocorticoid metabolism and her group has focussed on the role of hepatic 5α-reductase in diabetes and in dynamic methods to quantify these metabolic pathways in vivo using stable isotope tracers. She leads a team specialising in small molecule quantitative analysis in support of translational medicine. She takes an active role in teaching both Honours students (Endocrine Physiology and Pharmacology, Clinical Biochemistry) and post- graduate students. She is a Committee member of the Society for Endocrinology, the Chief Scientist Office, FWO (Flanders), and the Commonwealth Commission and an Editor for the British Journal of Pharmacology, a Specialty Chief Editor for Systems Endocrinology (Frontiers in Endocrinology) and an Associate Editor with Talanta.
Adam Rosebrock, PhD
Stony Brook School of Medicine
Dr. Adam Rosebrock is an assistant professor in the Department of Pathology at Stony Brook School of Medicine and the Stony Brook University Cancer Center. He has had longstanding interest in using “big data” to address fundamental biological questions. The focus of his research is on understanding the regulation of biochemical activities that underlie cell division, growth, and survival across diverse external states. The Rosebrock lab actively develops new experimental and analytical methods and builds genetic, hardware, and computational tools to enable high-throughput and high-content biology, with particular emphasis on quantitative mass-spectrometry metabolomics.
Nicola Zamboni, PhD
ETH Zurich
1994-1999: Master in Biotechnology, ETH Zürich
1999-2003: PhD, Institute of Biotechnology, ETH Zürich, Uwe Sauer and Prof. Jay Bailey
2004-2005: PostDoc, Genome Technology Center, Stanford University, Prof. Peter Oefner and John Ross
since 2005: Principal Investigator, Institute of Molecular Systems Biology, ETH Zürich
Gianfranco Frigerio
University of Milan
PhD student
PhD in Epidemiology, Environment and Public Healthcare
University of Milan (Italy)
Project title: Childhood obesity and biomarkers: evaluation of the level of persistent organic pollutants and metabolic profile
Evelyn Penaloza, PhD
Federal University of Rio de Janeiro
Federal University of Rio de Janeiro - Ph.D. Natural Products Chemistry
Federal University of Rio Grande do Sul - Msc. Pharmaceutical Sciences
University National Mayor de San Marcos - Bacharel of Pharmacy and Biochemistry
Looking for an opportunity to hone your interview skills? This is the place for those looking to transition in entry-level positions. Two interviewees will present their elevator pitch and respond to a series of interview questions from a panel of experts and/or hiring managers in a particular field. After their mock interview, the panelists will provide their feedback. This month
Salford Royal NHS Foundation Trust & University of Manchester
Laura Owen is a Consultant Clinical Scientist at Salford Royal NHS Foundation Trust and honorary senior lecturer at the University of Manchester where she teaches chromatography and mass spectrometry at Master’s level. Laura is also proud to be the chair of the practical training committee of MSACL EU and a past member of the endocrinology committee. While working at Wythenshawe hospital and in collaboration with the Christie hospital she became interested in the limitations of immunoassay measurement especially when using it in the breast cancer population. Laura developed and implemented the UK’s first LC-MS/MS assay for oestradiol in an NHS UKAS accredited laboratory which was made available for patient care and clinical trials.
Oestradiol (also spelled Estradiol) measurement by LC-MS/MS has demonstrated superior sensitivity and specificity over immunoassay but despite this, use of immunoassay remains commonplace. Measuring oestradiol by LC-MS/MS is not without its challenges for which there are several approaches. One particular challenge is the very low levels that there is a clinical need to measure accurately, especially in patients with breast cancer. This presentation will look at the issues around accurate measurement and review how different authors have approached them. It will also examine how oestradiol measurement is used in a breast cancer population as a guide for treatment decisions and how different analytical approaches might impact upon these decisions.
Hoda Safari Yazd University of Florida, MSACL Early Career Network
Early Career Network: Fireside Chat with Dr. David Pirman & Dr. Alla Kloss
David Pirman, PhD
Agios Pharmaceuticals
David Pirman is currently an Associate Director at Agios working in the metabolism and proteomics group. He and his team support numerous drug discovery programs at varying stages across the portfolio. He completed his training under Professor Richard Yost at the University of Florida developing quantitative MALDI MS imaging methods. He then spent a year at MD Anderson Cancer Center working on cancer lipid metabolism followed by a postdoctoral position at Pfizer further studying metabolic disease and building metabolomics analytical capabilities. David has been developing and using mass spectrometry methods to study disease metabolism applied to the drug discovery setting for 8+ years.
Alla Kloss, PhD
Sanofi
Alla Kloss is a Scientific Director at Analytical Research and Development Department in PDS, NA Hub, Sanofi where she leads a Biomarkers and Advanced Analytical Development group. Her group has established and validated an in-house metabolomics/lipidomics platform which includes both commercially available and novel, developed internally, tools for discovery of translational biomarkers. This platform is successfully used for discovery and identification of metabolic biomarkers, development of phenotypic screens, target credentialing, as well as in later phases of drug development.
Alla has been at Genzyme/Sanofi for 19 years, supporting broad range of programs from early discovery to Manufacturing. She has lead Manufacturing Forensics efforts at AR&D and brought to successful resolution over 25 manufacturing investigations.
Education:
MS in Chemical Engineering from The Institute of Technology (St. Petersburg Russia).
PhD in Physical/Analytical Chemistry from University of California, Davis
Post Doctoral studies at the University of Illinois at Urbana-Champaign.
Join our Fireside Chat with Dr. David Pirman and Dr. Alla Kloss to learn about a career after your studies in metabolomics/lipidomics. This session will be interactive and offers opportunities to network.
Supported by an Open Unrestricted Educational Grant
provided by
Vitamin K Metabolism in Elastic Fiber Degradation and COVID-19
Jody van den Ouweland, PhD
Canisius-Wilhelmina Hospital
Jody van den Ouweland is specialist in Laboratory Medicine and working as Laboratory Director at the Canisius-Wilhelmina Hospital, The Netherlands. He studied Chemistry at Leiden University and received his PhD degree in 1994 on the discovery of a type 2 diabetic subtype (MIDD). Areas of clinical interest are diabetes, endocrinology and clinical biomarkers. In the area of analytical chemistry his focus is on mass spectrometric and chromatographic methods for quantitative measurement of low molecular weight biomarkers, such as vitamins, steroids and amino acids. He is a member of the Dutch working group of Clinical Mass Spectrometry, member of the MSACL EU Scientific Board, and Editorial Board member of the Journal of Mass Spectrometry & Advances in the Clinical Lab.
Jona Walk, MD
Canisius-Wilhelmina Hospital, The Netherlands
Jona Walk is a resident physician specializing in Internal Medicine at the Canisius Wilhelmina Hospital in Nijmegen. She conducted her PhD research on cellular immune responses after vaccination with the human malaria parasite Plasmodium falciparum at the Radboud university medical center in Nijmegen. She is currently studying vitamin K metabolism as a possible factor in pulmonary damage and coagulopathy in COVID-19, and the potential role for vitamin K supplementation in the treatment of severe SARS-CoV-2 infections.
In this webinar we will present results from our recent study on vitamin K status in SARS-CoV-2 patients. We found severely impaired vitamin K-dependent activation of matrix-Gla-protein (MGP), strongly correlated with increased elastic fiber degradation (as measured by levels of plasma desmosine with LC-MS/MS). Our data suggest a mechanism of pneumonia-induced extrahepatic vitamin K depletion leading to accelerated elastic fiber damage in severe COVID-19 due to impaired activation of MGP. The talk includes a detailed description of the role of vitamin K in hepatic as well as extrahepatic metabolism and its inter-relationship with elastin calcification and elastin degradation as pathological processes that impair elastin
Get-the-Basics: Capillary Electrophoresis Mass Spectrometry (CE-MS)
Rob Haselberg, PhD
Vrije Universiteit Amsterdam
Dr. Rob Haselberg is an assistant professor at the Vrije Universiteit Amsterdam in the department of Chemistry and Pharmaceutical Sciences. He specialized over the last 10+ years in capillary electrophoresis and liquid chromatography hyphenated with mass spectrometry to characterize intact proteins. He is interested in determining protein heterogeneity, getting insights in degradation processes, mapping intentional modifications and studying protein-protein interactions. All of this is done in the context of biopharmaceutical, clinical, and doping analysis.
Classical electrophoresis has a long history in clinical diagnostics. Being used to separate proteins and nucleic acids, it is still an indispensable tool. Over the years, technological advances have allowed for these slab-gel format to be performed in capillaries enabling higher throughput and more accurate quantitation. However, capillary electrophoresis (CE) also has other application areas for clinical diagnostics, especially when hyphenated with mass spectrometry (MS). To show this added values and to understand and appreciate the diversity of this technique, in this seminar the basics of CE and its hyphenation with mass spectrometry will be covered. Separation mechanisms and technical / practical aspects will be covered, using (amongst others) data obtained in our lab. Moreover, some key applications of CE-MS related to clinical diagnostics will be highlighted. They focus on small molecules, lipids, but also intact proteins. Throughout the seminar and at the end there will be ample opportunity to ask questions.
Dr. Mark Marzinke is Professor of Pathology and Medicine in the Johns Hopkins University School of Medicine. He is board-certified in Clinical Chemistry by the American Board of Clinical Chemistry. He serves as the Director of the General Chemistry Laboratory at the Johns Hopkins Hospital and the Clinical Pharmacology Analytical Laboratory within the Division of Clinical Pharmacology. Dr. Marzinke is Co-Principal Investigator (PI) of the HIV Prevention Trials Network (HPTN) Laboratory Center (LC) and is the Director of the Clinical Laboratory Core for the Johns Hopkins Center for AIDS Research. His primary research interests are in the areas of antiretroviral pharmacology, HIV prevention science, mass spectrometry, pharmacogenetics and precision medicine, and laboratory automation. Dr. Marzinke has an active research program and serves as a principal investigator (PI) or co-investigator on a number of grants. He has collaborated on research to better characterize the multi-compartment pharmacology of antiretroviral agents when administered using alternative drug delivery systems using liquid chromatographic-mass spectrometric approaches. He has published more than 180 peer-reviewed articles, and holds leadership positions in several societies.
An overview of the fundamentals that are driving research and development with respect to Sample Preparation.
This is part of a series of Primers on topics relevant to Clinical Mass Spectrometry.
Learning objectives include:
1. To identify the importance of specimen processing in acquiring accurate results.
2. To describe how interferents can impact mass spectrometric results.
3. To weigh the benefits and limitations of different specimen preparation approaches for mass spectrometric assays using a fit-for-purpose approach
EDUCATION:
Graduate School: University of Virginia (Chemistry), Charlottesville, VA
Clinical Chemistry and Laboratory Medicine Fellowship: University of Virginia, Charlottesville, VA
CLINICAL:
Laboratory testing in Clinical Chemistry, Toxicology, Hemostasis, and Endocrinology.
RESEARCH:
Liquid chromatography mass spectrometry assay methods.
Dustin Bunch, PhD, DABCC
Nationwide Children's Hospital
Dustin R. Bunch, is an Asst. Director of Clinical Chemistry & Co-Director Laboratory Informatics at Nationwide Children's Hospital. His research focuses small molecule analysis by mass spectrometry in a clinical setting and clinical informatics.
Hubert W. Vesper, Ph.D., is the director of the Clinical Standardization Programs at the Centers for Disease Control and Prevention’s (CDC) National Center for Environmental Health. He leads CDC’s clinical laboratory standardization programs to improve the diagnosis, treatment, and prevention of selected chronic diseases and oversees and represents specific biomonitoring programs to assess human exposure to environmental chemicals and its potential impact on human health. He also is co-chair of the steering committee of the Partnership for Accuracy in Tests for Hormones (PATH), a member of the steering committee of the National Glycohemoglobin Standardization Program, and an adjunct faculty member in the Nutrition and Health Sciences Program at Emory University. Previously he was a consultant at the Kuwait Institute for Scientific Research, co-chair of the Cardiovascular Biomarker Standardization Steering Committee, and a member of the World Health Organization (WHO)/Pan American Health Organization/CDC Emergency Response Team. He received his B.S. in food science and M.Sc. in food chemistry from the University of Karlsruhe, Germany, and his Ph.D. from the Technical University of Munich, Germany.
Going Viral: Increasing Access to COVID-19 Testing with Open Source Tools &
Data Automation for Pooled NAT Testing of SARS CoV-2: Rapid Development with R
Daniel Holmes, MD, FRCPC
St. Paul’s Hospital
Daniel Holmes did his undergraduate training in Chemistry and Physics at the University of Toronto before deciding to pursue medicine as a career. He attended medical school at the University of British Columbia where pathology became his area of major interest. The strong influence of his academic mentors led him to enter the Medical Biochemistry residency training program at UBC. This allowed him to use his background knowledge of chemistry in application to medicine. Areas of clinical interest are diagnostic lipidology/endocrinology and research interests are in the utilization of mathematics and computer diagnostics to laboratory medicine.
Patrick Mathias, MD, PhD
University of Washington
Patrick Mathias, M.D., Ph.D., is a board-certified clinical pathologist and Associate Director of Informatics for UW Laboratory Medicine.
Lab medicine has large impact on the general practice of medicine. It is key to correctly diagnosing diseases and selecting the right treatments for patients. Dr. Mathias's goal is to combine technical and medical knowledge to fulfill the triple aim--reduce the per capita cost of health care, improve the health of populations and most importantly improve the patient experience of care.
Dr. Mathias earned his M.D. and Ph.D. from the University of Illinois. His clinical and research interests include clinical informatics, clinical chemistry and molecular diagnostics.
Speaker: Dr. Patrick Mathias
The COVID-19 pandemic has introduced challenge upon challenge for health care systems throughout the US and the world, from implementing new workflows in support of delivering routine care to improving access to testing to navigating constrained supply chains. Clinical laboratories have been critical to the COVID-19 response, as identification of cases with testing is a critical step in containing and managing the SARS-CoV-2 virus. The University of Washington Virology Laboratory has played a key role expanding access to COVID-19 testing across the Pacific Northwest, scaling from performing 5,000 tests per month to 5,000 tests per day and growing. Open source software tools have supported this rapid growth along every step of our journey. In this talk, we will discuss the key capabilities R and Python have enabled that have helped us navigate the daily challenges of managing staffing and turnaround times, adjusting operations in response to supply chain limitations, and enabling testing at scale for the population outside of typical health care settings.
Speaker: Dr. Dan Holmes
Dan Holmes will discuss end-to-end liquid handling, data and reporting automation for pooled SARS CoV-2 testing using R, R Shiny and other open source tools. The talk will discuss development, validation, workflow and user experience with an aim to increase testing throughput, improve staff experience and decrease the risk of error.
Ample time for discussion post-presentation will be available.
Robin oversees all Research &Product Development programs within Metabolomic Diagnostics, a company focused on developing early pregnancy risk stratification tests for obstetrical syndromes like preeclampsia and preterm birth. He trained as an analytical chemist, specialized in mass spectrometry, and received a PhD from the University of Antwerp in 2006. After 7 years with a Belgian proteomics biomarker discovery company, where he led the preeclampsia biomarker discovery program, Robin joined Metabolomic Diagnostics in 2013. Since then, he and his team established a translational research workflow which aims to overcome the challenges of translating promising biomarkers into novel products.
Operating at the interface of translational research and commercialisation, he has always keenly engaged in conversations with members of the clinical research community on how to deliver on a shared mission of improving pregnancy outcomes.
Robin has co-authored 20+ original research articles and is a named inventor on 10 patent applications.
Grégoire Thomas, PhD
SQU4RE
Grégoire is a biostatistician specialised in clinical diagnostics and medical devices. Based on complexity estimations, he implements data analysis strategies and statistical frameworks which mitigate risks and therefore increase the chance of successful outcomes. This is achieved by working at the crossroads of statistics, machine learning, medical sciences, and epidemiology whilst adopting IT solutions which are compliant with regulatory and legal frameworks. As a consultant, Grégoire has an established track record of fruitful collaborations with both academic and industry partners.
The area under the receiver operating characteristic (AUROC) curve is a widely used statistic to evaluate performance of prognostic and diagnostic tests. Because AUROC does not depend on disease prevalence, the statistic has also gained prominence in biomarker discovery and development, as it enables biomarker evaluation using cost-effective case-control study designs.
However, end-users in clinical settings typically assess the merits of prognostic / diagnostic tests in function of patient harm and benefit. Disease prevalence and clinical context are critical determinants in clinical utility evaluations and therefore different statistics, like positive and negative predictive values (PPV and NPV), which account for these determinants are typically used to gauge clinical utility. Albeit most biomarker work is performed with the goal of improving clinical care, clinical utility is rarely considered during test development.
To address this lacuna, we devised a method for plotting PPV or NPV criteria, which account for prevalence, in the receiver operating characteristic (ROC) space. Herewith, test developers and clinical end-users are provided with a common framework to discuss and evaluate prognostic / diagnostic test performances.
In this talk we will briefly review key concepts like Sensitivity (Sn), Specificity (Sp) and Prevalence (Pr), and how they are used to create ROC curves (Sn, Sp) and calculate predictive values (Sn, Sp, Pr). We will highlight the limitations of solely depending on AUROC in test evaluations and the importance of considering the shape of ROC curves. Then we will demonstrate how PPV and NPV criteria can be plotted on the ROC space and how this information can be used to discuss test performance in function of clinical utility with different stakeholders. We will conclude with the demonstration of a freely accessible web-tool developed to allow people to explore the dynamic interplay between the test characteristics Sn, Sp, Pr, AUROC, ROC curve shape, PPV and NPV.
Carmen Wiley, PhD, DABCC, FADLM Incyte Diagnostics
Clinical Cases
Carmen Wiley, PhD, DABCC, FADLM
Incyte Diagnostics
Dr. Carmen Wiley was the 2019 - 2020 President of AACC. Recently she returned to the clinical practice of laboratory medicine and serves as Clinical Medical Director at Incyte Diagnostics. In this role, she supports the new clinical lab facility located in Spokane Valley and acts as the Medical Director over the clinical labs at Providence Sacred Heart Medical Center, Holy Family, My Carmel, and St. Joseph’s.
Dr. Wiley holds a Bachelor’s degree in Chemistry from the University of Minnesota, a Master’s degree in Organic Chemistry from the University of Washington, a Doctoral degree in Organic Chemistry from the University of Washington, and was a COMACC Accredited Fellow at the Mayo School of Medicine. She is board certified by American Board of Clinical Chemistry (ABCC) and a Fellow of the Academy of the American Association of Clinical Chemistry (FAACC).
Most recently, she was the Chief Medical Officer of a start-up company based in Oakdale, MN. Previously, she was a Regional Manager of Scientific Affairs – Cardiac at Roche Diagnostics. In this role, she was responsible for leading and developing the Medical & Scientific Liaisons in their relationships with the medical/scientific community, with the objective of critical scientific exchange including medical/scientific education. Dr. Wiley played a key role in providing support to healthcare professionals as well as internal Roche scientific groups and local business teams. Dr. Wiley was the Scientific Director at PAML where she was responsible for the medical and scientific oversight of all laboratory testing and oversaw all aspects of PAML’s research and development program. Prior to that, Dr. Wiley was Co-Director of Chemistry, Immunology, and Point of Care at Providence Health and Services, Sacred Heart Hospital in Spokane, WA and the Head of Clinical Chemistry in the Division of Laboratory Medicine and Pathology at the Marshfield Clinic in Marshfield, WI.
Dr. Wiley, her husband of 21 years and two kids enjoy time spent with their three dogs. She loves hiking, camping, and knitting. She is a native to Minnesota, but now considers Spokane, WA her home.
Nicole Tolan, PhD
Harvard Medical School
Dennis Dietzen, PhD
Washington University School of Medicine
My research activities focus on improving existing analytic diagnostic tools and expanding the repertoire of informative biomolecules available for disease detection in children. We have developed novel analytic tools for the detection of inborn errors of metabolism and drug exposure in children and continue to explore the value of broad metabolic profiling in conditions such as pre-eclampsia, intrauterine growth retardation, liver failure, and neonatal hypoglycemia.
Mass spectrometry continues to play a prominent role in the field of laboratory medicine. In this session, each speaker will highlight a clinical case where Mass Spec Analysis has made all the difference in a patient's care and outcome.
After completing this activity, the learner will be able to:
1. site examples where mass spectrometry made a difference in patient care
2. describe how mass spectrometry could play an important in their institutions
3. summarize the role of mass spectrometry played in each of these case studies
Christopher Anderton, PhD Environmental Molecular Sciences Laboratory
Peggi Angel, PhD MUSC Proteomics Center
From the Operating Room to the Mass Spec: Handling and Storage of Human Tissue Samples
Heather Jensen Smith, PhD
University of Nebraska Medical Center
Dr. Heather Jensen Smith is a Research Assistant Professor, Director of the Multiphoton Intravital and Tissue Imaging Research Core (MITI), and member of the Rapid Autopsy Programs for Pancreas and Prostate at the University of Nebraska Medical Center (UNMC). She earned her PhD in Biomedical Sciences from Creighton University in 2006.
Over the last 15 years Dr. Jensen Smith has managed and/or Directed research imaging cores at both Creighton University and UNMC, supporting a broad spectrum of biomedical studies, as well as, her studies investigating the use of endogenous fluorophores as biomarkers of disease progression. As part of the Fred and Pamela Buffett Cancer Center and Eppley Institute for Research in Cancer and Allied Diseases, Dr. Jensen Smith is focused on building a Preclinical Imaging Center integrating clinical, translational, and basic research(ers). In collaboration with Dr. Paul Grandgenett (Director RAP), Dr. Jensen Smith has helped conduct, collect, maintain, and distribute research specimens from 139 autopsies (as of 2020) totaling over 22,000 samples and 60 liters of biofluids.
Kyana Garza, PhD
Johns Hopkins University School of Medicine
Yan Ru Su, PhD
Vanderbilt
We will discuss patient-specific effects, sample collection, transport and handling of samples, and tissue preparation when acquiring and interpreting mass spectrometry data. We will especially focus on how these steps effect imaging mass spectrometry data, but many of these topics translate universally across mass spectrometry approaches in general.
This will be an open forum with predefined topics and panelists to guide the conversation.
Protein Poly-ADP-Ribosylation: Identification, Regulation and Translation
Yonghao Yu, PhD
University of Texas, Southwestern
Dr. Yonghao Yu received his Ph.D. in Chemistry from the University of California, Berkeley in 2006 under the direction of Julie Leary, where he developed mass spectrometric approaches for the study of tyrosine sulfation, a protein post-translational modification that is implicated in regulating protein-protein interactions in the extracellular space. In 2007, Dr. Yu joined the laboratories of Steven Gygi and John Blenis in the Department of Cell Biology at Harvard Medical School for his post-doctoral training. There he developed quantitative mass spectrometric strategies for the study of protein phosphorylation.
In 2012, Dr. Yu began his independent research career as an Assistant Professor in the Department of Biochemistry at UT Southwestern Medical Center. He was promoted to Associate Professor with tenure in 2017. Throughout his career, Dr. Yu has been the recipient of numerous awards for his research, including the Tuberous Sclerosis Alliance Postdoctoral Fellowship, a CPRIT Scholar in Cancer Research award, a Virginia Murchison Linthicum Scholar in Medical Research award, a Research Scholar award from the American Cancer Society, a UT System Rising STARs Award and most recently, an R35 MIRA award from NIGMS. He has served on many NIH and DoD advisory panels, including as a current member of the NIH Enabling Bioanalytical and Imaging Technologies (EBIT) Study Section.
The long-term goals of the Yu lab are to develop cutting-edge, mass spectrometry-based proteomic technologies, and applying them to systematically identify and characterize novel protein modification events implicated in various pathophysiological conditions. These data-driven strategies are then combined with classical biochemistry approaches to identify aberrant protein modification patterns, decipher the mechanisms of their deregulation, establish the functional consequences of these molecular events, facilitate the development of relevant therapeutic strategies, and finally, identify proteomic signatures that may serve as diagnostic, prognostic or predictive biomarkers for the relevant diseases (e.g., cancer, diabetes and neurodegenerative disease).
Our understanding of how the biology of various diseases relates to the central dogma that DNA encodes RNA, which encodes protein has been buoyed by rapid technological advances in DNA and RNA sequencing and has led to some of the first advances in personalized medicine. However, characterization of the final and arguably most actionable element of the central dogma, protein, has lagged behind. We are interested in developing mass spectrometry-based quantitative proteomic technologies for the comprehensive characterization of the proteome, with a particular focus on post-translational modifications (PTMs)
Poly-ADP-ribosylation (PARylation) is a protein posttranslational modification (PTM) that was first documented in 1963. PARylation is catalyzed by a family of enzymes called Poly-ADP-ribose polymerases (PARPs). In particular, PARP1 is a nuclear protein that is activated as a result of sensing DNA strand breaks. The critical roles of PARP1 in mediating DNA repair and also cell death provide the rationale for developing PARP1 inhibitors to treat a number of human diseases, including cancer and ischemia reperfusion injury. Indeed, late-stage clinical studies revealed that PARP1 inhibitor treatment significantly prolonged progression-free survival of BRCA-deficient ovarian and breast cancer patients. This led to the recent FDA approval of four PARP1 inhibitors in these two indications. However, the signaling mechanism of PARP enzymes is poorly understood, because PARylation is a labile and heterogenous modification.
To address these pressing questions, we developed a large-scale mass spectrometric approach towards comprehensive characterization of the Asp- and Glu-PARylated proteome. Remarkably, the modified proteins are involved in not only DNA damage repair, but also a surprisingly wide array of other nuclear functions. Using a quantitative mass spectrometry experiment, we also identified many previously unknown PARP1 downstream targets, whose PARylation is sensitive to clinically relevant PARP1 inhibitors. More recently, we generated a cell-specific atlas for protein PARylation map in breast cancer. In doing so, we identified PARylation signatures that correlated with the selective cytotoxicity of PARP1 inhibitors in certain breast cancer cells. These results provide potential predictive biomarkers for PARP1 inhibitors. Finally, using the PROTAC technology, we recently developed a small molecule compound that selectively induces the degradation of PARP1. This compound is able to inhibit PARP1, without eliciting the deleterious effects of PARP1 trapping. We showed that this
Using Mass Spectrometry and Proteomics to Understand the Mechanism Involved in Cystic Fibrosis
Sandra Pankow, PhD
The Scripps Research Institute
INTRODUCTION: Cystic Fibrosis is a disease caused by mutations in the cystic fibrosis ion transport regulator gene (CFTR). The most common mutation, deletion of Phe at position 508 (DF508), results in a loss of function phenotype that causes a large number of clinical symptoms including chronic respiratory infections. At the protein level, the DF508 mutation causes the protein to misfold which results in rapid degradation of the protein in the ER.
OBJECTIVES: The objective of this study is to understand the mechanisms involved in regulating protein misfolding to learn how to rescue the misfolded protein. A detailed understanding of the mechanism should lead to the identification of drug targets for treatment of the disease.
METHODS: Mass spectrometry-based proteomics was used to identify the proteins interacting with wild type CFTR and DF508 CFTR to identify those proteins interacting with the mutant protein, but not the wild type. Proteins interacting uniquely with the mutant were knocked down to identify those proteins whose
Join us for some informal networking and to hear from Michelle Reid, Aruna Vigneshwari, and L. Tamina Hagemann on the research they have been working on in their laboratories! Employers, be sure to join us to find your next perfect hire!
Anas Abdel Rahman, PhD King Faisal Specialist Hospital and Research Center
Mass Spectrometry Provides a Universal Solution for Expansion of Newborn Screening
Michael Gelb, PhD
University of Washington
Michael H. Gelb is Professor of Chemistry and Barbara L. Weinstein Endowed Chair in Chemistry, Adjunct Professor of Biochemistry at the University of Washington. Major developments in the Gelb lab include discovery of protein prenylation, development of ICAT proteomic reagents, identification of phospholipases involved in lipid mediator generation, development of anti-parasite drugs, and development of mass spectrometry for newborn screening. Awards include: Repligen Award in Chemistry of Biological Processes (Amer. Chem. Soc.), Univ.of Washington Faculty Lecture Award, Gustavus John Esselen Award (Harvard Univ.), AAAS Fellow, NIH Merit Award, Medicines for Malaria Project of the Year Award, Pfizer Award in Enzyme Chemistry, ICI Pharmaceuticals Award for Excellence in Chemistry. The Gelb lab has published more than 500 papers and 100 patents in biological chemistry. The Gelb laboratory has developed mass spectrometry for worldwide newborn screening of lysosomal storage diseases (the latest expansion of newborn screening panels).
Mass spectrometry has a strong presence in newborn screening laboratories because of the ability to quantify numerous metabolites in dried blood spots on newborn screening cards. Over the past decade mass spectrometry has been developed to measure enzymatic activities in dried blood spots. We will present an 18-plex mass spectrometry assay that provides enzymatic activities and biomarkers for lysosomal diseases and allows consolidation with existing mass spectrometry newborn screening panels. In the second part of the presentation we will show the feasibility of using mass spectrometry for proteomics-based newborn screening. This allows screening for a panel of treatable diseaes for which no other methods exists.
As more and more inborn errors become treatable, in part due to gene therapy, it will be important to develop a universal screening platform that allows high throughput, consolidated newborn screening. Despite great progress in DNA sequencing technology, this will not replace biochemical newborn screening in the foreseable future.
Early Career Network: Fireside Mentor Chat with Dr. David Tabb
David Tabb, PhD
Stellenbosch University
David Tabb, born in the U.S. Midwest, surprisingly finds himself living in South Africa after a fifteen-year transition from assistant professor to associate professor to “full” professor. While in the United States, he conducted his research in a state university, a private research institute, a national laboratory, and a private university. Since 2015, he has enjoyed the moderate climate of Cape Town, where he is completing a five-year contract in tuberculosis biomarker research at Stellenbosch University. He has survived and occasionally thrived in the rich world of clinical proteomics, where he has specialized in the informatics of protein identification from tandem mass spectrometry. He was particularly fortunate to be a bioinformatics lead for the Clinical Proteomics Technology Assessment for Cancer (CPTAC) during the first ten years of that program’s operations. His hobbies include choral singing, computer upgrading, board gaming, and cat pestering.
Proteomics is a field in constant demand in academia, industry, and the clinical lab. With the rapidly changing technology in the proteomics world, bioinformaticians who have an intimate understanding of mass spectrometry as well as computational skills are much needed. Join our Fireside Chat with clinical proteomics bioinformatician, Dr. David Tabb to learn more about a career in bioinformatics from all angles.
This session will be interactive and offers opportunities to network.
The 3D Proteome and the Potential for Conformational Biomarkers
Casimir Bamberger, PhD
The Scripps Research Institute
*This talk was originally scheduled to be presented at MSACL 2020 US by John Yates. It is expected to be about 20 minutes, not including Q&A.
INTRODUCTION: Proteins have exquisite three-dimensional structure. Their structures dictate the functions and interactions within the cell. Most of what we know about the structures of proteins comes from methods like x-ray crystallography, NMR and more recently cyro-EM. These methods are all in vitro methods that often look at proteins as single entities or as a protein complex. What is often missing is the in vivo context to the protein structure, e.g. what is the structure that exists in the cell. Several mass spectrometry-based methods are emerging to examine the 3D proteome or the conformations of proteins in their in vivo context.
OBJECTIVES: The primary objective of this work is to develop methods to measure the "structures" or confirmations of protein in the in vivo environment and to apply them to common diseases.
Exploratory Analysis of Small Molecules Guided by Chemical Functionalities
Christina Ferreira, PhD
Purdue Metabolite Profiling Facility at Bindley Bioscience Center
Christina R. Ferreira works as Lipidomics Scientist in the Metabolite Profiling Facility at Purdue University. Her main research interest is the application of the MRM-profiling method for the exploratory analysis of lipids and metabolites in developmental biology models. At Prof. Cooks lab, she created the MRM-profiling method and contributes to diverse projects from the Cooks lab related to further developing this method. Dr. Ferreira also supports the application MRM-profiling in research projects served by the multi-user Purdue Metabolite Profiling Facility at Bindley Bioscience Center. She is also the project manager for a large effort (Purdue Make-It System) for high-throughput screening and analysis of chemical reactions using DESI-MS.
R. Graham Cooks, PhD
Purdue University
R. Graham Cooks is the Henry Bohn Hass Distinguished Professor in the Department of Chemistry at Purdue University. He has served as major professor to 150 PhD students. Dr. Cooks’ was a pioneer in the conception and implementation of tandem mass spectrometry (MS/MS) and of desorption ionization, especially molecular secondary ionization mass spectrometry (SIMS). His work also includes the development of miniature portable mass spectrometers using ambient ionization and application of this combination to problems of trace chemical analysis at point-of-care. His interests in the fundamentals of ion chemistry focus on chiral analysis based on the kinetics of cluster ion fragmentation. His group also studies collisions of ions at surfaces for new methods of molecular surface tailoring and analysis, and nanomaterials preparation by soft-landing of ions and charged droplets. Dr. Cooks also launched new methods of small scale synthesis based on accelerated reactions in microdroplets and incorporated this capability into high throughput screening instrumentation based on DESI. This screening capability extends to enzyme assays. Dr. Cooks has been recognized with the Mass Spectrometry and the Analytical Chemistry awards of the American Chemical Society, the Robert Boyle Medal and the Centennial Prize of the Royal Society of Chemistry, and the Camille & Henry Dreyfus Prize in the Chemical Sciences. He is an elected fellow of the American Academy of Arts and Sciences, the Academy of Inventors and the U.S. National Academy of Sciences.
In this talk, we invite the audience to critically investigate the predominant mass spectrometry workflows used for the exploratory analysis of small molecules and discuss its analytical aspects. We will then present an approach for exploratory lipidomics and metabolomics, multiple reaction monitoring (MRM)-profiling, which initially explores small molecules present in biological samples based on their chemical functionalities using precursor ion (Prec) and neutral loss (NL) scans without the use of chromatographic separation. In a second step the Prec and NL information is translated into MRM scans and these are used to obtain mass profiles to be compared among samples by univariate and multivariate statistical methods. The MRM profiling methodology is characterized by high speed and excellent classification of samples. Identification and quantitation of individual molecules is also achieved.
Join the FeMS network (Females in Mass Spectrometry) with guest Michelle Reid for a discussion on mentorship and to learn about a new FeMS mentoring program. You may signup to participate in the mentoring program using the Mentorship Program signup form.
There will be time for discussion and a breakout networking session. This is a fun, informal way to stay connected and meet people in the field.
Please join us for another Mass Spec Mixer featuring presentations from Grad Students Transitioning to PostDocs: Ettore Gilardoni, Daniel Mouzo Calzadilla and Alexandra Iakab. There will be time for networking, all are welcome, employers encouraged!
Hoda Safari Yazd University of Florida, MSACL Early Career Network
Niloofar Abolhasani Khaje The University of Mississippi
Clinical Chemistry Career Exploration Series: Industry
Carmen Wiley, PhD, DABCC, FADLM
Incyte Diagnostics
Dr. Carmen Wiley was the 2019 - 2020 President of AACC. Recently she returned to the clinical practice of laboratory medicine and serves as Clinical Medical Director at Incyte Diagnostics. In this role, she supports the new clinical lab facility located in Spokane Valley and acts as the Medical Director over the clinical labs at Providence Sacred Heart Medical Center, Holy Family, My Carmel, and St. Joseph’s.
Dr. Wiley holds a Bachelor’s degree in Chemistry from the University of Minnesota, a Master’s degree in Organic Chemistry from the University of Washington, a Doctoral degree in Organic Chemistry from the University of Washington, and was a COMACC Accredited Fellow at the Mayo School of Medicine. She is board certified by American Board of Clinical Chemistry (ABCC) and a Fellow of the Academy of the American Association of Clinical Chemistry (FAACC).
Most recently, she was the Chief Medical Officer of a start-up company based in Oakdale, MN. Previously, she was a Regional Manager of Scientific Affairs – Cardiac at Roche Diagnostics. In this role, she was responsible for leading and developing the Medical & Scientific Liaisons in their relationships with the medical/scientific community, with the objective of critical scientific exchange including medical/scientific education. Dr. Wiley played a key role in providing support to healthcare professionals as well as internal Roche scientific groups and local business teams. Dr. Wiley was the Scientific Director at PAML where she was responsible for the medical and scientific oversight of all laboratory testing and oversaw all aspects of PAML’s research and development program. Prior to that, Dr. Wiley was Co-Director of Chemistry, Immunology, and Point of Care at Providence Health and Services, Sacred Heart Hospital in Spokane, WA and the Head of Clinical Chemistry in the Division of Laboratory Medicine and Pathology at the Marshfield Clinic in Marshfield, WI.
Dr. Wiley, her husband of 21 years and two kids enjoy time spent with their three dogs. She loves hiking, camping, and knitting. She is a native to Minnesota, but now considers Spokane, WA her home.
Cory Bystrom, PhD
Ultragenyx
Jeanne Rhea-McManus, PhD, ABCC, NRCC
Siemens Healthineers
Dr. Jeanne Rhea-McManus completed her PhD in Genetics at the University of Georgia followed by a post-doctoral fellowship within the Department of Pathology and Laboratory Medicine at Emory University in Atlanta, Georgia. There she served as the Technical Coordinator and Assistant Director of the Emory Clinical Translational Research Laboratory and specialized in the development of mass spectrometry methods for use in patient care. Since 2014, Dr. Rhea-McManus has served as a Medical Officer for Siemens Healthineers where one of her primary roles is to ensure the safety, efficacy, and sustainability of products that are put on the market and used for patient care. In addition to this role, she also organizes the Siemens Healthineers Medical and Scientific Learning Exchange program which as been held annually since 2016 and serves to bridge the knowledge gap that exists between the training received by medical professionals and IVD manufacturers.
What does clinical chemistry have to do with industry? What opportunities are available for me as a clinical chemistry? Join in our live interview of two clinical chemists who will share their career journey towards earning their clinical chemistry certification and their current position in various industries. Bring your questions and be ready for the networking opportunity after the interview!
Prof Roessner has obtained her Diploma in Biochemistry at the University of Potsdam and the John Innes Institute in Norwich, UK after which she pursued a PhD in Plant Biochemistry at the Max-Planck-Institute for Molecular Plant Physiology in Germany, where she developed novel GC-MS methods to analyse metabolites in plants. Together with the application of sophisticated data mining, the field of metabolomics was born and is today an important tool in biological sciences, systems biology and biomarker discovery. In 2003 she moved to Australia where she established a GC-MS and LC-MS based metabolomics platform as part of the Australian Centre for Plant Functional Genomics for which she led the node at the University of Melbourne. In addition, since 2007, Prof Roessner has been involved in the setup and lead of Metabolomics Australia (MA), a federal and state government funded national metabolomics service facility and now leads the MA node at the University of Melbourne. In 2013, Prof Roessner was awarded an Australian Research Council Future Fellowship to establish her own research program applying Imaging Mass Spectrometry for spatial metabolite and lipid analyses to understand root metabolism under salinity stress. Currently her research program uses metabolomics and lipidomics technologies to decipher how plant roots interact with beneficial microbes under abiotic stress conditions. In 2018, Prof Roessner took up the position as Head of School, School of BioSciences, University of Melbourne.
Join us for our next FeMS Happy Hour! We will be following our usual format with small group breakout room discussions followed by Ute Roesnner presenting on Resilience, and a time for Q&A and Discussion. All are welcome!
Niloofar Abolhasani Khaje The University of Mississippi
Nazmin Bithi, PhD University of Utah School of Medicine
Clinical Chemistry Career Exploration Series: Government
Candice Ulmer, PhD
Centers for Disease Control and Prevention
Dr. Candice Ulmer, a native of South Carolina, graduated from the College of Charleston in 2012 with a B. S. in Chemistry and Biochemistry. While at the College of Charleston, Candice investigated the pharmaceutical photodegradation of NSAIDs using ESI-LC-MS/MS under the direction of Dr. Wendy Cory. Dr. Ulmer graduated (May 2016) with a PhD in Chemistry as a McKnight Doctoral Fellow from the University of Florida in Dr. Richard Yost’s research group. For her doctoral work, she applied UHPLC-HRMS techniques to profile the metabolome/lipidome of human cells and tissues to better understand the disease etiology of Type 1 Diabetes and melanoma skin cancer. Dr. Ulmer’s research comprised experience with various modes of ionization (e.g., MALDI, ESI, APCI, DESI, FlowProbe, and DART). She also incorporated novel stable isotope labeling methodologies such as Isotopic Ratio Outlier Analysis (IROA) to aid in the identification of metabolites as compound identification is still considered a bottleneck in metabolomics studies. In addition to her duties as a graduate student, she was an active researcher with the NIH-funded Southeast Center for Integrated Metabolomics (SECIM). Dr. Ulmer was a member of the Florida mass spec discussion group and the ASMS diversity committee in an effort to increase diversity at conferences and ASMS supported events. Dr. Candice Ulmer was a NIST NRC Post-Doctoral Research Associate (June 2016 – August 2017) and was involved with multi-omic UHPLC-HRMS method development, the first lipidomics interlaboratory study, and experiments that monitored the effects of environmental exposures on human/marine life. Dr. Ulmer is currently a Clinical Chemist Battelle contractor at the Centers for Disease Control and Prevention in Atlanta, GA (National Center for Environmental Health, Division of Laboratory Sciences, Clinical Chemistry Branch). Her responsibilities include the accurate measurement of chronic disease biomarkers and the assessment of clinical analytical methods in patient care.
David Herold, MD, PhD
MSACL, University of California San Diego and VA San Diego Medical Center
David Herold received his BS (1966) in Chemistry from Tulane University. He completed his MA (1972) in Chemistry at the University of North Carolina-Chapel Hill, served 5 years in the USAF, received his MD (1979) and PhD (1982) at the University of Utah and then completed a Clinical Pathology residency (1982) at the University of Virginia. In 1982 he joined the University of Virginia faculty. In 1991 he moved to the University of California, San Diego and is now Professor of Pathology. He has authored and co-authored over 80 scientific publications and presented at numerous international scientific conferences. Inspired by the 2007 ASMS Asilomar conference on clinical mass spectrometry, Dr. Herold co-founded MSACL. From 2008 to the present, he has served as CEO, Executive Board Chair and Global Scientific Coordinator of MSACL. MSACL's mission is to further the accumulation and sharing of expertise in mass spectrometry and other advanced technologies in the clinical laboratory through educational advancement. MSACL will continue building the foundation for the adoption of technology in the clinical laboratory, including data science, based on the belief that this will provide more accurate, precise and timely laboratory results at lower overall costs that will result in better patient care and outcomes.
What roles do clinical chemists play in the government? Which agencies do they work for? Join in our live interview of two clinical chemists who will share their career journey towards earning their clinical chemistry certification and their positions in government. Bring your questions and be ready for the networking opportunity after the interview!
Ethan Yang, PhD Johns Hopkins University, MSACL Early Career Network
Hoda Safari Yazd University of Florida, MSACL Early Career Network
Clinical Chemistry Career Exploration Series: Academia
Stefani Thomas, PhD, DABCC, NRCC
University of Minnesota
Dr. Stefani Thomas is an Assistant Professor in the Department of Laboratory Medicine and Pathology at the University of Minnesota, and the Associate Medical Director of the M Health Fairview University of Minnesota Medical Center West Bank Laboratory. She earned a BA in Biological Sciences from Dartmouth College, a PhD in Pharmaceutical Sciences from the University of Southern California, and she completed a Clinical Chemistry postdoctoral fellowship at Johns Hopkins. Her research program at the University of Minnesota utilizes mass spectrometry-based clinical proteomics for therapeutic and diagnostic biomarker development.
Jacqueline Hubbard, PhD, DABCC
Beth Israel Deaconess Medical Center, Harvard Medical School
Jacqueline Hubbard received her BS degree in Biochemistry from the University of Vermont. She then earned her MS and PhD in Biochemistry and Molecular Biology from the University of California, Riverside (UCR). Following a one year postdoc at UCR, Dr. Hubbard completed a Fellowship in Clinical Chemistry at the University of California, San Diego Health. She is board certified in Clinical Chemistry by the American Board of Clinical Chemistry. In 2019, she took a position as an Assistant Professor in the Department of Pathology and Laboratory Medicine at the Geisel School of Medicine at Dartmouth and as the Assistant Director of Clinical Chemistry at Dartmouth-Hitchcock Medical Center. There, she focused on developing and validating drugs of abuse assays and SARS-CoV-2 serology testing. After serving as a Lab Director for a small reference laboratory, she joined Beth Israel Deaconess Medical Center as the Co-Director of Clinical Chemistry and Director of Toxicology in 2024. She is also an Assistant Professor of Pathology for Harvard Medical School. Her research focus still includes mass spectrometry method development and toxicology test interpretation.
What positions in academia are available to clinical chemists in academia? Can a clinical chemistry fellowship help with tenure track professorship? Join in our live interview of two clinical chemists who will share their career journey towards earning their clinical chemistry certification and their current position as professors at universities. Bring your questions and be ready for the networking opportunity after the interview!
University of Texas Southwestern Medical Center at Dallas
Nicholas is a fifth year PhD candidate in Molecular Biophysics with a focus in Computational and Systems Biology at The University of Texas Southwestern Medical Center under Dr. Prashant Mishra. His interest is in using isotope tracing mass spectrometry to perform metabolic flux analysis to investigate alterations in metabolism as a result of dysfunctional mitochondria.
Alyson Black
Medical University of South Carolina
Alyson is a 4th year PhD student working under the mentorship of Drs. Anand Mehta and Richard Drake. She has developed a new tool for analysis of glycoproteins from biofluids and is using this to discover new cancer biomarkers. She is passionate about interdisciplinary science communication and teaching.
Even though our scientific lives have vastly moved to a virtual space, the clock keeps ticking and graduate school & post doc positions are ending for many. To help promote networking for those searching for jobs in this crazy time, Females in Mass Spectrometry (FeMS) would like to institute Transition Talks where ALL graduate students and post docs in MS-related fields within 1 year of transition are welcome to participate. Additionally, students looking for an internship may apply.
The Transition Talks will be 10 minute informal talks, followed by 5 minutes of questions, where the speakers:
>Introduce themselves
>Give an overview of their current research
>Explain their desired transition
Transition Talks will be presented virtually at FeMS Mass Spec Mixers, which will be held on the last Thursday of every month starting on 07/30/2020. Mass Spec Mixers will enable informal networking and connections between the speakers and the scientific community so that job postings can be quickly communicated to those on the market. Anyone who would like to grow their network is encouraged to attend!
If you are interested in giving a Transition Talk, please fill out the google form linked below and we will schedule you depending on the timeline of your transition and your preferred time. Sign up to present a Transition Talk Here
Ethan Yang, PhD Johns Hopkins University, MSACL Early Career Network
Clinical Chemistry Career Exploration Series: Introduction
Andy Hoofnagle, MD, PhD
University of Washington
Dr. Hoofnagle's laboratory focuses on the precise quantification of recognized protein biomarkers in human plasma using LC-MRM/MS. In addition, they have worked to develop novel assays for the quantification of small molecules in clinical and research settings. His laboratory also studies the role that the systemic inflammation plays in the pathophysiology of obesity, diabetes, and cardiovascular disease.
Robert Fitzgerald, PhD, DABCC
University of California San Diego
Robert L. Fitzgerald, PhD, DABCC Dr. Fitzgerald received his BS degree in Chemistry at Loyola College of Maryland, and his PhD in Pharmacology/Toxicology at the Medical College of Virginia/Virginia Commonwealth University. After two and a half years as a forensic toxicologist for the State of Virginia, he took a position as the Director of the Mass Spectrometry Laboratory at the San Diego VA Hospital. Currently, Dr. Fitzgerald is a Professor in the Department of Pathology at the University of California, San Diego where he is the director of the toxicology laboratory and associate director of the clinical chemistry laboratory. He is board certified in toxicology and clinical chemistry by the American Board of Clinical Chemistry. He is the director of the clinical chemistry fellowship at UCSD.
Joe M. El-Khoury, PhD, DABCC, FAACC
Yale School of Medicine
Dr. Joe El-Khoury is Associate Professor of Laboratory Medicine at Yale School of Medicine, Director of the Clinical Chemistry Lab and Fellowship program at Yale-New Haven Health. He is board certified by the American Board of Clinical Chemistry (ABCC) and a fellow of the AACC Academy. He currently serves on the Board of Directors of AACC, as well as Chair of the Committee on Kidney Diseases for IFCC. His research interests are pre-analytical errors, biomarkers of kidney disease, and liquid chromatography-mass spectrometry in the clinical laboratory.
Not sure what to do with your PhD in mass spectrometry after graduation? Interested in having a direct impact on patient outcomes? Consider a career in clinical chemistry! Come and learn about what this field is all about and what it takes to become a clinical chemist, including the fellowship application process, the fellowship itself, and much more. Live interview of Clinical Chemistry Program Heads followed by open discussion and networking sessions in breakout rooms.
Hoda Safari Yazd University of Florida, MSACL Early Career Network
Early Career Network: Fireside Mentor Chat with Tiffany Payne
Tiffany Payne
Agilent
Tiffany Payne is the Marketing Director for Clinical Diagnostic Analytical Instruments at Agilent Technologies. She studied mass spectrometry at the University of the Pacific under David Sparkman and holds an M.S. in Chemistry and Pharmaceutical Sciences. She started her career at Varían, Inc. as an Application Scientist and joined Agilent after their acquisition of Varían in 2010. Since joining Agilent Tiffany has held a number of marketing positions in Product Management and Segment Marketing.
Curious about Career options in Industry? Join this Fireside Chat with Agilent Director of Marketing, Tiffany Payne.
Learn what career paths are available at Agilent, tips regarding hiring practices and application strategies, paths to management positions, and making the pivot from academia to industry.
This session will be interactive and offers networking opportunities.
Andrea Geistanger is Head of MassSpec Biostatistics, at Roche Diagnostics in Germany. Her department of biostatisticians supports system and assay development through the whole life cycle of Roche’s cobas products. Her team is involved in the early development phases, including biomarker search projects with machine learning and multivariate statistics analysis. During product development phases, Andrea’s data analysts support scientists in experimental planning with Design of experiments, as well as in the experiment of validation studies according to regulatory requirements. Furthermore, they develop standardization schemes and calibration concepts for cobas analyzers. Throughout the development phase, software tools are designed and developed as needed. These programs are also made available to a broader community through open software projects.
Andrea Geistanger recently gave a talk at MSACL Connect on the mcr and VCA R packages for method comparison and precision analysis. That talk was dedicated to statistical tools, the actual one will address the soft topics of these experiments, as study design, analysis and interpretation.
Within this 2 hours workshop important points of method comparison and precision experiments in terms of study design, data analysis and interpretation of results will be covered.
Method comparison experiments address the trueness of an analytical method or the comparison of two analytical measurement methods for the same measurand. The study design addresses not only the question of how many samples to incorporate, but also how to distribute these samples among the measuring interval and which samples to use. From a statistical point of view, method comparison data results in error-in-variables regression models, which need special regression techniques as Deming or Passing-Bablok regression. The main ideas behind these regression techniques will be explained. In addition it will be discussed how to interprete the results of regression estimation and its relationship to the calculated bias.
The second half of the workshop covers precision experiments and the set-up of nested precision designs. Variance-components estimation is explained and the approach to deduce from the lowest precision level to the highest the individual components. Finally, the interpretation of the different variability measures is shown.
How is the emergence of hemp affecting the Clinical space? Synthesis, certification and clinical evaluation of 7-Hydroxy and 7-Carboxy Cannabidiol Certified Reference Materials in plasma samples by LC-MS/MS
Heather Lima, PhD
MilliporeSigma
I joined Cerilliant Corporation at MilliporeSigma as a Senior Scientist in 2012 after earning a Ph.D. in Chemistry at the University of Texas at Arlington. My graduate research focused on the total synthesis of imidazole-containing natural products, and a manufacturing technology internship at Abbott Laboratories focused on API manufacturing process improvements and scale up. I earned a B.S. in Biochemistry in 2005 also at the University of Texas at Arlington.
I have extensive experience in reference material development and certification. My expertise includes design and synthesis of drugs, their metabolites, API impurities and stable isotope labelled internal standards, particularly steroids, cannabinoids, opiates and opioids. In June 2021, I took on the role of Senior R&D Manager of the Synthesis Department. Currently, I oversee synthesis operations of catalog and new products supporting the manufacture of Certified Reference Materials (CRM’s) at the Round Rock site as well as a diverse portfolio of custom synthesis projects.
Raymond Suhandynata, PhD DABCC
University of California, San Diego
Dr. Suhandynata is an Assistant Professor at the University of California San Diego with appointments in the Skaggs School of Pharmacy and Department of Pathology. He serves as the Associate Laboratory Director for the CMCR reference laboratory and the Associate Director of the UCSD ComACC clinical chemistry fellowship. He completed his Clinical Chemistry fellowship training at the UC San Diego Center for Advanced Laboratory Medicine, under the direction of Dr. Robert Fitzgerald. He has extensive experience with applications of mass spectrometry in research, pre-clinical, and clinical laboratories. Areas of interest include phospho-proteomics to identify novel kinase targets by LC-MS/MS, SUMO proteomics to identify cellular signals involved in chromosome segregation, utilization of MALDI-TOF MS in to identify antibiotic resistant bacteria in the clinical specimens, and development of targeted LC-MRM/PRM assays for small molecules and peptides. Addtionally, he as made significant contributions during the COVID-19 pandemic, validating several COVID-19 serology LDTs at UCSD Health.
Cannabidiol (CBD), a non-psychoactive constituent of hemp, has been increasingly promoted and studied for pharmacological uses as regulations regarding cannabis and hemp evolve rapidly at a state and federal level. In response to these recent regulations, novel Cannabinoid Certified Reference Materials (CRMs) and testing methods have been developed for the main human metabolites of CBD, 7-hydroxy cannabidiol (7-OH CBD) and 7-carboxy cannabidiol (7-COOH CBD). We will touch on recent legal changes for cannabinoid testing in a Clinical setting, as well as discuss the synthesis, certification, and evaluation of these cannabinoid CRMs in patient whole blood samples at the Center for Advanced Laboratory Medicine at UCSD.
Grace van der Gugten, B.Sc. Chemistry Alberta Precision Laboratories
MS Quantitation and/or Screening of Monoclonal Antibody Therapeutics: the Good, the Bad, the Ugly
Paula Ladwig, MS, MT (ASCP)
Mayo Clinic
Paula M. Ladwig, M.S., MT (ASCP), is a Principal Developer with the Clinical Mass Spectrometry Development Laboratory, Department of Laboratory Medicine and Pathology at Mayo Clinic in Rochester, MN. She has over 15 years of experience in the development and validation of new mass spectrometry tests. Her interests include the implementation of therapeutic drug monitoring of monoclonal antibody therapeutics by mass spectrometry.
Session Overview
The clinical laboratory will have many roles as monoclonal antibody therapeutics (t-mAbs) expand: identifying potential interferences in routine immunoassays; developing new assays to differentiate a t-mAb from an endogenous, disease-causing plasma cell clone and monitoring therapeutic drugs for better patient outcomes and assessing loss of response to therapy. This session will provide an overview of mass spec techniques available to the clinical laboratory for t-mAb detection and quantitation along with their advantages and disadvantages. Finally this session will offer a few examples of hurdles in the implementation into the clinical laboratory setting.
Target Audience
This session is intended for clinical laboratory directors and pathologists, clinical technologists, IVD manufacturers, pharmaceutical scientists, and anyone interested in the mass spectrometry applications for therapeutic monoclonal antibodies especially those involved in development of new methods for t-mAb monitoring.
Needs Assessment
There are over 60 different therapeutic monoclonal antibodies (t-mAbs) approved by the FDA; used to treat a variety of diseases. The market for monoclonal antibodies is rapidly growing, with over 500 new t-mAbs in several stages of development. Laboratorians are quite familiar with the detection, screening, and quantitative therapeutic drug monitoring for small molecules as the methodologies have been well established, therapeutic ranges for many drugs have been defined, and the metabolic pathways for many small molecules have been elucidated in detail. However, this is not the case for the t-mAbs. The detection, screening, and quantitative measurement of these monoclonal antibodies require different technologies.
Mass spectrometry is an important tool in the field of t-mAbs; mostly because it is relatively simple and so versatile once you understand how to apply the basic principles, challenges and limitations of each different approach and instrumentation. This session will provide examples of approaches for mass spectrometry assay development for chimeric, humanized and fully human t-mAbs quantitation; from peptide by quadrupole MS to intact or subunit detection by time-of-flight or orbitrap MS.
Following the completion of this session, the participant will be able to:
1. Describe mass spectrometry techniques available for the assessment of monoclonal antibody therapeutics along with their advantages and disadvantages.
FeMS Happy Hour: Featuring advice from MJ Paulines from Merck
MJ Paulines, PhD
Merck
Join the FeMS network (Females in Mass Spectrometry) with guest MJ Paulines from Merck for tips, tricks and advice for successful industry and pharmaceutical job interviews.
There will be time for discussion and a breakout networking session. This is a fun, informal way to stay connected and meet people in the field.
All are encouraged to join!
Follow FeMS on Twitter: @FemalesMassSpec
Join the FeMS LinkedIn Group.
Theodore Alexandrov, PhD European Molecular Biology Laboratory (EMBL) Heidelberg
Poster Tour with Theodore Alexandrov
Annapurna Pamreddy, PhD
The University of Texas Health San Antonio
My PhD and first postdoc focused on analysis of peptides, various nano-materials and antibiotic compounds using mass spectrometry-based techniques, and the localization and distribution study of various drugs in rat plasma and brain tissues via Mass Spectrometry Imaging (MSI). I recently joined Dr. Kumar Sharma’s Lab (Center for Renal Precision Medicine) at the University of Texas Health, San Antonio, to continue my postdoctoral studies, and am mainly focused on the kidney precision medicine project (KPMP) which extends to the study of diabetic complications [e.g., diabetic kidney diseases (DKD) and diabetic ketoacidosis (DKA)], spatial metabolomics and MSI in kidney tissues. I have also been involved in developing novel quantitative methods for targeted metabolomics for plasma and urine samples, and have extensive experience in method development for small molecules in biosamples.
Emily Sekera, PhD
The Ohio State University
Emily Sekera earned her B.S. in chemistry at Rochester Institute of Technology in 2015. She then completed her graduate studies in analytical chemistry at University at Buffalo, in the laboratory of Prof. Troy D. Wood studying disease states using -omics based techniques and high resolution mass spectrometry. She is currently a postdoctoral researcher working under Dr. Amanda B. Hummon investigating at the intersection of cancer biology and analytical chemistry.
Calvin Blaschke
Medical University of South Carolina
I started conducting research in my sophmore year at Coker College in Dr. Joseph Flaherty's lab, where I focused on the phenotypic characterization of knock-out mutants of Fusarium graminearum with a focus on the systems of conidiagenesis and stress response. I was fortunate enough to spend a semester in Dr. Stephen Rossiter's lab at Queen Mary University of London analyzing and interpreting RNA-seq data sets in order to examine if there was differential expression of genes associated with sensory organs in bats with different diets. I participated in the University of Chicago's Cell and Molecular Biology REU program and conducted a project on optimizing the conditions for a dinucleosome remodeling assay in Dr. Alexander Ruthenburg's lab. I am currently pursuing a Ph.D. in Biomedical Sciences at the Medical University of South Carolina in Dr. Richard Drake's lab in order to contribute to the understanding of cancer glycobiology using mass spectrometry imaging.
Crystal Pace
North Carolina State University
I graduated from Meredith College in 2017 with a B.S. in Chemistry (Magna Cum Laude). While at Meredith College, I double majored in Chemistry and Environmental Sustainability with a minor in mathematics. Currently, I am a third year PhD Candidate in the Department of Chemistry at North Carolina State University under the advisement of Professor David Muddiman. My research focuses on the development of mass spectrometry imaging methodologies by infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) for applications in exposomics.
Kaylie Kirkwood
North Carolina State University
I am a rising second-year chemistry graduate student working under the advisement of Dr. Erin Baker at North Carolina State University (NCSU). Thus far, my research has been focused on the development of multidimensional lipid spectral libraries for the rapid and confident identification of lipid species in complex samples. This work is essential for current and future applications in our lab and the broader lipidomics community. I primarily focus on clinical and environmental applications ranging from elucidating lipid markers associated with smoke inhalation injury to evaluating lipid dysregulation in plants following exposure to perfluoroalkyl substances. I am currently serving as the Communications Committee Chair of Females in Mass Spectrometry (FeMS). Prior to graduate school, I completed a B.S. in chemistry with a minor in biological sciences at NCSU. I did undergraduate research with Dr. David Muddiman, where I utilized capillary electrophoresis-mass spectrometry for the measurement of small molecules associated with amyotrophic lateral sclerosis.
Grace van der Gugten, B.Sc. Chemistry Alberta Precision Laboratories
Poster Tour with Grace van der Gugten
Jennifer Kemp
Mayo Clinic
Graduated from the University of Wisconsin Lacrosse in 2007. Started my career at Mayo Clinic in 2007 as Clinical Laboratory Scientist. In 2010, I was promoted to a Technical Specialist I role in the Endocrinology Lab which then became the Clinical Mass Spec Lab. In 2016 I transitioned to a Developer role and just recently I was promoted to a Principal Developer within the Mass Spec Development lab.
Ilja Burdman
Heinrich Heine University, Institute of Clinical Pharmacy and Pharmacotherapy
I studied pharmacy and graduated from the Heinrich Heine University in 2016. Currently, I’m a PhD student at the institute of clinical pharmacy and pharmacotherapy. My research focuses on biomarker quantification using hybrid LBA/LC-HRMS assays.
Medical School
MD - Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
Residency
Clinical Pathology - Massachusetts General Hospital, Boston, MA (Chief Resident)
Fellowship
Transfusion Medicine - Harvard Medical School, Cambridge, MA
Board Certification
Clinical Pathology
Graduate Degree
PhD in Cell and Molecular Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
Michael Kane, PhD, MA
Yale University School of Public Health
Michael Kane is an Assistant Professor in Yale University's Biostatistics Department. He is interested in Scalable Statistical/Machine Learning, Statistical Computing, and Applied Probability.
Joseph Rickert, MA, MS
RStudio
Joseph is RStudio’s “Ambassador at Large” for all things R, editor of the R Views blog, and RStudio’s representative on the R Consortium’s board of directors. Joseph came to RStudio via Revolution Analytics and Microsoft where he was a data scientist, blogger and community manager. Before joining Revolution Analytics Joseph worked as a statistician for a small healthcare economics consulting firm, and before that he held a variety of technical, marketing and sales positions while working for startups that spanned multiple industries including government contracting, local area networks, disk drives and test equipment. Joseph studied Classics and Mathematics as an undergraduate at Franklin & Marshall College and earned an M.A. in Humanities and an M.S. in Statistics from the California State University.
Lindsay Bazydlo, PhD
University of Virginia
EDUCATION:
Graduate School: University of Virginia (Chemistry), Charlottesville, VA
Clinical Chemistry and Laboratory Medicine Fellowship: University of Virginia, Charlottesville, VA
CLINICAL:
Laboratory testing in Clinical Chemistry, Toxicology, Hemostasis, and Endocrinology.
RESEARCH:
Liquid chromatography mass spectrometry assay methods.
Shannon Haymond, PhD
Northwestern University Feinberg School of Medicine
My lab performs research and clinical testing using mass spectrometry methods, develops new assays, and applies data analytics to enable improved quality and efficiency. My computational pathology efforts are aimed at building the capacity for advanced data analytics in the department through innovations in infrastructure, education, and research to facilitate data-informed decision making for clinical care, operations, and quality assurance.
Daniel Holmes, MD, FRCPC
St. Paul’s Hospital
Daniel Holmes did his undergraduate training in Chemistry and Physics at the University of Toronto before deciding to pursue medicine as a career. He attended medical school at the University of British Columbia where pathology became his area of major interest. The strong influence of his academic mentors led him to enter the Medical Biochemistry residency training program at UBC. This allowed him to use his background knowledge of chemistry in application to medicine. Areas of clinical interest are diagnostic lipidology/endocrinology and research interests are in the utilization of mathematics and computer diagnostics to laboratory medicine.
R is a freely available open-source programming language and a powerful statistical computing environment that is extremely popular among statisticians and data scientists. R is ideally suited for building customized applications for clinical operations, however many (real and perceived) hurdles exist in operationalizing R in healthcare in general, and in the labs in particular. This session is hosted by the organizers of R/Medicine, an annual conference aiming to promote the R ecosystem in clinical research and practice. This will be a highly interactive session aimed to share insights and experiences both of the discussants and participants, with the aim of facilitating the integration of the R ecosystem into clinical laboratory practice.
Alfonso Limon is the Chief Liaison of R&D for Oneirix Labs, a consulting company developing market-leading technologies resulting in high-value intellectual property. Previously, he was the Director of Research at Intersection Medical, leading groups developing optimal algorithms for the management of congestive heart failure. Alfonso earned a B.S. in Mechanical Engineering from San Diego State University, a M.S. in Mathematics from Claremont Graduate University and Ph.D. in Computational Science from their joint program.
An overview of the fundamentals that are driving research and development in the field of Data Science.
This is part of a series of Primers on topics relevant to Clinical Mass Spectrometry.
Learning objectives include:
1. Be able to define what Data Science is, why it matters, and why you personally should care. What is the clinical relevance?
2. Define any terminology that is specific to this field.
3. Describe how it works, what are the methods and workflows used when studying this field and/or how is it implemented in clinical labs.
4. Identify any challenges to implementation/adoption, where do the opportunities lie?
Hoda Safari Yazd University of Florida, MSACL Early Career Network
Early Career Network: Fireside Chat with Dr Rick Yost
Richard Yost, PhD
University of Florida
Dr. Yost is the University Professor and Head of Analytical Chemistry at the University of Florida. He is also director of the Southeast Center for Integrated Metabolomics (SECIM) and of NIH’s Metabolomics Consortium Coordinating Center (M3C). He is recognized internationally as a leader in the field of analytical chemistry, particularly tandem mass spectrometry (MS/MS). His research has been recognized with the ASMS Award for Distinguished Contribution in Mass Spectrometry, the MSACL Award for Distinguished Contribution to Clinical Mass Spectrometry, and the Florida Academy of Sciences Medal. Dr. Yost currently serves as President of the American Society for Mass Spectrometry (ASMS).
All are welcome to join the Early Career Network for an informal chat with mentoring legend, Dr Yost. Bring your career development related questions. This is a networking opportunity you won't want to miss.
FeMS Happy Hour: Featuring Coalition of Black Mass Spectrometrists Founders
Candice Ulmer, PhD
Centers for Disease Control and Prevention
Dr. Candice Ulmer, a native of South Carolina, graduated from the College of Charleston in 2012 with a B. S. in Chemistry and Biochemistry. While at the College of Charleston, Candice investigated the pharmaceutical photodegradation of NSAIDs using ESI-LC-MS/MS under the direction of Dr. Wendy Cory. Dr. Ulmer graduated (May 2016) with a PhD in Chemistry as a McKnight Doctoral Fellow from the University of Florida in Dr. Richard Yost’s research group. For her doctoral work, she applied UHPLC-HRMS techniques to profile the metabolome/lipidome of human cells and tissues to better understand the disease etiology of Type 1 Diabetes and melanoma skin cancer. Dr. Ulmer’s research comprised experience with various modes of ionization (e.g., MALDI, ESI, APCI, DESI, FlowProbe, and DART). She also incorporated novel stable isotope labeling methodologies such as Isotopic Ratio Outlier Analysis (IROA) to aid in the identification of metabolites as compound identification is still considered a bottleneck in metabolomics studies. In addition to her duties as a graduate student, she was an active researcher with the NIH-funded Southeast Center for Integrated Metabolomics (SECIM). Dr. Ulmer was a member of the Florida mass spec discussion group and the ASMS diversity committee in an effort to increase diversity at conferences and ASMS supported events. Dr. Candice Ulmer was a NIST NRC Post-Doctoral Research Associate (June 2016 – August 2017) and was involved with multi-omic UHPLC-HRMS method development, the first lipidomics interlaboratory study, and experiments that monitored the effects of environmental exposures on human/marine life. Dr. Ulmer is currently a Clinical Chemist Battelle contractor at the Centers for Disease Control and Prevention in Atlanta, GA (National Center for Environmental Health, Division of Laboratory Sciences, Clinical Chemistry Branch). Her responsibilities include the accurate measurement of chronic disease biomarkers and the assessment of clinical analytical methods in patient care.
Michelle Reid, PhD
ETH Zürich
Christina M. Jones, Ph.D.
National Institute of Standards and Technology
Join the FeMS network (Females in Mass Spectrometry) for a presentation from special guests Drs. Candice Ulmer, Michelle Reid, and Christina M. Jones, founders of Black People Meet @ASMS.
There will be time for discussion and a breakout networking session. This is a fun, informal way to stay connected and meet people in the field.
MSACL Recognizes the Contributions of Alan Rockwood to Clinical Mass Spectrometry
Distinguished Contribution Award
Moderator(s):
Marilyn Huestis, PhD Huestis & Smith Toxicology LLC
Shannon Haymond, PhD Northwestern University Feinberg School of Medicine
Stephen Master, MD, PhD, FADLM Children's Hospital of Philadelphia
Richard Yost, PhD University of Florida
My Path to Enlightenment or How I Became a Clinical Mass Spectrometristand Clinical Chemist
Alan Rockwood, PhD, DABCC
University of Utah, School of Medicine
Alan Rockwood, PhD, DABCC is Professor (Clinical) Emeritus of Pathology at the University of Utah School of Medicine in Salt Lake City, Utah, USA. Originally trained in Physical Chemistry, he performed research on the fundamentals of mass spectrometry and instrumentation development before focusing his career on Clinical Chemistry. He became certified by the American Board of Clinical Chemistry and has held a Certificate of Qualification in Clinical Chemistry from the New York State Board of Health. Currently, his primary area of research is the development of mass spectrometry-based quantitative assays for targeted analytes of clinical interest, including small molecules and more recently proteins and peptides. Additionally, he maintains a smaller research effort on fundamentals of mass spectrometry, particularly novel approaches for isotopic profile calculations. He has published >150 papers in peer reviewed journals.
Like many people in the field of Clinical Chemistry, I arrived here by an indirect route. In this presentation I give an account of the path I traveled to get here, discussing my development as a scientist and ultimately my embrace of Clinical Chemistry and Clinical Mass Spectrometry as career choice for the last half of my career journey, including some of the people who influenced or mentored me, a few stops along the way, and some of the lessons learned along the way, both from a scientific and a personal perspective. Included will be some projects and discoveries that I regard as successes as well as a few that were less successful, and lessons that can be drawn from both.
Assistant Professor at the Maastricht MultiModal Molecular Imaging (M4I) institute, I have more than 8 years of experience in the MSI imaging fields and had the opportunity to gain insights on different aspects, including instrumental development, sample preparation and quantification. Since I have earned my PhD at the School of Pharmaceutical Sciences (University of Geneva), I am now devoted to demonstrate how MSI can be employed to improve the accuracy of cancer diagnostics. I am strongly motivated by the translational aspect between the development of innovative instrumentation and direct application to clinical research – with a special focus on intraoperative mass spectrometry – and by the close collaboration with the Surgeons and Pathologists of the Maastricht University Medical Center + (MUMC+), and with the RWTH Aachen in Germany.
An overview of the fundamentals that are driving research and development in the field of Mass Spec Imaging.
This is part of a series of Primers on topics relevant to Clinical Mass Spectrometry.
Learning objectives include:
1. Be able to define what MS Imaging is, why it matters, and why you personally should care. What is the clinical relevance?
2. Understand what role mass spectrometry plays in this field. Where does mass spec fit in to the big picture of the field?
3. Define any terminology that is specific to this field.
4. Describe how it works, what are the methods and workflows used when studying this field and/or how is it implemented in clinical labs.
5. Identify any challenges to implementation/adoption, where do the opportunities lie?
Financial Considerations for Purchasing a Mass Spectrometer
Joe M. El-Khoury, PhD, DABCC, FAACC
Yale School of Medicine
Dr. Joe El-Khoury is Associate Professor of Laboratory Medicine at Yale School of Medicine, Director of the Clinical Chemistry Lab and Fellowship program at Yale-New Haven Health. He is board certified by the American Board of Clinical Chemistry (ABCC) and a fellow of the AACC Academy. He currently serves on the Board of Directors of AACC, as well as Chair of the Committee on Kidney Diseases for IFCC. His research interests are pre-analytical errors, biomarkers of kidney disease, and liquid chromatography-mass spectrometry in the clinical laboratory.
This informal Practical Training session will include a presentation on Financial Considerations for Purchasing a Mass Spectrometer, as well as offer small group discussion and networking opportunities.
1. Describe the clinical and monetary benefits of purchasing a mass spectrometry system.
2. Identify different models for financing a mass spectrometry system purchase.
3. Participate in effective negotiations with vendors.
Dr. Drake earned his PhD in Biochemistry and Molecular Biology from the University of Kentucky in 1990. Over the course of his career, first as a faculty member at the University of Arkansas for Medical Sciences, then the Eastern Virginia Medical School, and finally for the past seven years at the Medical University of South Carolina (MUSC), Dr. Drake has published over 150 manuscripts in peer-reviewed journals, developed 4 patents, and edited 2 books. He has been Director of the MUSC Proteomics Center since 2011, and in close collaboration with Dr. Ball will serve as Director of the DDRCC Proteomics Core. The Core will provide highly specialized expertise and advanced instrumentation for the application of imaging mass spectrometry (IMS) technologies to gastrointestinal and liver research questions (includes both experimental and clinical projects).
Since 2002, Dr. Drake has developed multiple MS-based approaches for profiling clinical biofluids and tissues, and specializes in the analysis of glycans and glycoprotein biomarkers. In the past five years, his laboratory has developed a robust and highly novel IMS approach for the analysis of N-linked glycans in tissues. This method is of great utility as it can be used with any FFPE (formalin-fixed paraffin-embedded) or frozen tissue, ranging from clinical samples to tissues harvested from genetically engineered animal models. His glycan IMS approach continues to generate high-content N-glycome maps which provide detailed information on potential marker functions and localization in tissues. This in turn is facilitating further IMS method development for other types of glycan targets, such as O-glycans and heparin/chondroitin sulfate glycosaminoglycans, as well as glycoprotein post-translational modifications (PTMs).
An overview of the fundamentals that are driving research and development in the field of Glycomics.
This is part of a series of Primers on topics relevant to Clinical Mass Spectrometry.
Learning objectives include:
1. Be able to define what Glycomics is, why it matters, and why you personally should care. What is the clinical relevance?
2. Understand what role mass spectrometry plays in this field. Where does mass spec fit in to the big picture of the field?
3. Define any terminology that is specific to this field.
4. Describe how it works, what are the methods and workflows used when studying this field and/or how is it implemented in clinical labs.
5. Identify any challenges to implementation/adoption, where do the opportunities lie?
I graduated with a PhD from Dalhousie University in Halifax, NS, Canada in 2014 where I worked on developing and applying quantitative proteomics workflows for biomarker discovery. I then completed a Clinical Biochemistry Fellowship in Calgary, AB, Canada in 2016 before moving on to work as a Clinical Biochemist in the Fraser Health region in British Columbia, Canada. During this time I gained significant experience in using R and RStudio, writing numerous shiny apps to perform QC management and to streamline LC-MS/MS data workflows. In 2019, I moved to my current position in Calgary where I head the Mass Spectrometry testing facility for Alberta Precision Laboratories. Primarily focussed on toxicology testing, I have overseen a transition towards more endocrine testing and eliminated low-throughput GC-MS workflows in favour of targeted, MRM based LC-MS analyses. My research is focused on promoting LC-MS technologies and development of tools and workflows to bring targeted proteomics methodologies to routine clinical application.
A follow up to the presentation from May 20, 2020 entitled
An overview of the fundamentals that are driving research and development in the field of Proteomics.
This is part of a series of Primers on topics relevant to Clinical Mass Spectrometry.
Learning objectives include:
1. Be able to define what Proteomics is, why it matters, and why you personally should care. What is the clinical relevance?
2. Understand what role mass spectrometry plays in this field. Where does mass spec fit in to the big picture of the field?
3. Define any terminology that is specific to this field.
4. Describe how it works, what are the methods and workflows used when studying this field and/or how is it implemented in clinical labs.
5. Identify any challenges to implementation/adoption, where do the opportunities lie?
Bo Burla, PhD Sling @ National University of Singapore
Get-the-Basics: Lipidomics Primer
Anne K. Bendt, PhD
Singapore Lipidomics Incubator (SLING), National University of Singapore
Anne K Bendt studied Biology focusing on marine biotechnology (Greifswald University, Germany), followed by a PhD in Biochemistry (Cologne University, Germany) employing proteomics and transcriptomics. Driven by her fascination for infectious diseases, she joined the National University of Singapore (NUS) in 2004 to develop lipidomics tools for tuberculosis studies. She is now a Principal Investigator at the Life Sciences Institute, NUS, focussing on translation of mass spec technologies into clinical applications, and serving as the Deputy Director of the Singapore Lipidomics Incubator (SLING) taking care of operations and commercialization.
An overview of the fundamentals that are driving research and development in the field of Lipidomics.
This is part of a series of Primers on topics relevant to Clinical Mass Spectrometry.
Learning objectives include:
1. Be able to define what Lipidomics is, why it matters, and why you personally should care. What is the clinical relevance?
2. Understand what role mass spectrometry plays in this field. Where does mass spec fit in to the big picture of the field?
3. Define any terminology that is specific to this field.
4. Describe how it works, what are the methods and workflows used when studying this field and/or how is it implemented in clinical labs.
5. Identify any challenges to implementation/adoption, where do the opportunities lie?
European Molecular Biology Laboratory (EMBL) Heidelberg
Theodore Alexandrov is a group leader at the European Molecular Biology Laboratory (EMBL) in Heidelberg, the head of the EMBL Metabolomics Core Facility and an Assistant Adjunct Professor at the Skaggs School of Pharmacy, University of California San Diego. The Alexandrov team at EMBL aims to reveal secrets of metabolism in time and space in tissues and single cells by developing experimental and computational methods. The team unites interdisciplinary scientists from biology, chemistry, and computer science as well as software and machine learning engineers. Theodore Alexandrov is a grantee of an ERC Consolidator project focused on studying metabolism in single cells, as well as of various other European, national, NIH, and industrially-funded projects. He has co-founded and scientifically directed the company SCiLS and has over 70 journal publications and patents in spatial omics.
PhD 2007, St. Petersburg State University, Russia
Postdoctoral research at the University of Bremen, Germany
Group leader, University of Bremen, Germany
Assistant Adjunct Professor, University of California San Diego, USA
Team leader at EMBL since 2014.
The METASPACE platform hosts an engine for metabolite annotation of imaging mass spectrometry data as well as a spatial metabolite knowledgebase of the metabolites from hundreds of public datasets provided by the community.
Workshop on building compelling, professional presentations
Karen Mahooti, MBA
Articulate Consulting
Karen holds an MBA from the Yale University School of Management and is founder and principal at Articulate Consulting. Karen has provided training in presentation development skills to professionals around the world from executives and managers to analysts, consultants, and graduate students. In addition, over her career as both a management consultant and a marketing professional for a Fortune 20 company, Karen has created a multitude of clear and compelling presentations to help senior executives and board members of large companies make better strategic decisions. She understands first-hand the challenges of creating presentations when the stakes are high and clients' expectations are even higher. Karen's style is both visionary and practical. She seeks to inspire others to have confidence in what they can accomplish with their presentations, and also to give them the concrete know-how and tools they need to immediately begin creating presentations that give them the influence they desire.
This is a one hour primer packed with actionable steps that will have a positive impact on how you communicate your science in presentations.
Karen will discuss secrets to unlocking success in your presentation storyboarding, visual design, and oral delivery.
Several aspects of Karen's full-length course will be covered, pulling from:
John R. Yates is the Ernest W. Hahn Professor in the Departments of Molecular Medicine and Neurobiology at The Scripps Research Institute. His research interests include development of integrated methods for tandem mass spectrometry analysis of protein mixtures, bioinformatics using mass spectrometry data, and biological studies involving proteomics. He is the lead inventor of the SEQUEST software for correlating tandem mass spectrometry data to sequences in the database and developer of the shotgun proteomics technique for the analysis of protein mixtures. His laboratory has developed the use of proteomic techniques to analyze protein complexes, posttranslational modifications, organelles and quantitative analysis of protein expression for the discovery of new biology. Many proteomic approaches developed by Yates have become a national and international resource to many investigators in the scientific community. He has received the American Society for Mass Spectrometry research award, the Pehr Edman Award in Protein Chemistry, the American Society for Mass Spectrometry Biemann Medal, the HUPO Distinguished Achievement Award in Proteomics, Herbert Sober Award from the ASBMB, and the Christian Anfinsen Award from The Protein Society, the 2015 ACS’s Analytical Chemistry award, 2015 The Ralph N. Adams Award in Bioanalytical Chemistry, the 2018 Thomson Medal from the International Mass Spectrometry Society, and the 2019 John B. Fenn Distinguished Contribution to Mass Spectrometry award from the ASMS. He was ranked by Citation Impact, Science Watch as one of the Top 100 Chemists for the decade, 2000-2010. He was #1 on a List of Most Influential in Analytical Chemistry compiled by The Analytical Scientist 10/30/2013 and is on the List Of Most Highly Influential Biomedical Researchers, 1996-2011, European J. Clinical Investigation 2013, 43, 1339-1365 and the Thomson Reuters 2015 List of Highly Cited Scientists. He has published over 950 scientific articles with >125,000 citations, and an H index of 174 (Google Scholar). Dr. Yates served as an Associate Editor at Analytical Chemistry for 15 years and is currently the Editor in Chief at the Journal of Proteome Research.
Developments in mass spectrometers over the last decade have been numerous, but there are some clear trends. The drive to increase confidence in the identification of peptides and post-translational modifications pushed the development of high-resolution and high-mass accuracy instruments, most notably Orbitrap and time-of-flight (TOF) mass analyzers. Improvements in mass resolution in these instruments resulted in an increase in the mass range for effective analysis, precipitating greater interest in the
Evolving Role of Nominal and High Resolution Mass Spectroscopy in Routine Toxicology Casework
Thomas Rosano, PhD, FABFT, DABCC
National Toxicology Center; Albany Medical College
Dr. Rosano is board certified in forensic toxicology by the American Board of Forensic Toxicologists and in clinical chemistry by the American Board of Clinical Chemistry. For over 35 years Dr. Rosano has been director of Clinical Chemistry and Toxicology at the Albany Medical Center Hospital where in 1993 he expanded toxicology services to include postmortem toxicology services for a 22 county region. During his career at the Albany Medical Center Dr. Rosano has progressed to tenured professor of Laboratory Medicine at the Albany Medical College where he has lectured and mentored medical and graduate students along with residents and fellows. In 2018 Dr. Rosano transitioned to toxicologist and director of the National Toxicology Center at the Center for Medical Science in Albany, New York and was promoted to Professor Emeritus in Laboratory Medicine at the Albany Medical College. His current focus is on court-ordered and addiction medicine casework and the advancement of clinical and forensic toxicology through innovations in high-volume definitive screening and applications of high-resolution mass spectroscopy.
Advancing analytical technology serves as the foundation of our toxicology practice and the explosion in pharmaceutical and illicit drug use now mandates the application of definitive testing technology in both our screening and confirmatory test protocols. While nominal mass GC-MS traditionally served as the analytical technology for confirmatory drug testing, the transition to liquid chromatography coupled with tandem mass spectroscopy has largely occurred and has brought with it an emerging application of high resolution mass spectroscopy. As definitive methods further the molecular identification and certainty of drug and metabolite confirmation work, our screening protocols in many areas of clinical toxicology still rely on presumptive methods with their high false negative rates and lack of selectivity. Conversion to definitive methods of screening with expanded drug panels is clearly needed but the challenges of high-volume screening with mass spectrometry has slowed the conversion to definitive screening across many areas of clinical toxicology. The hurdles on the way to definitive screening include automated sample preparation, rapid chromatography separation, analyte-specific matrix normalization, data management, alternative confirmatory methodology and interpretive reporting of findings. The presentation will focus on one laboratory
Grace van der Gugten, B.Sc. Chemistry Alberta Precision Laboratories
Anne K. Bendt, PhD Singapore Lipidomics Incubator (SLING), National University of Singapore
Externally hosted activity.
FeMS Happy Hour with guest Yu Xia
Yu Xia, PhD
Tsinghua University
Dr. Yu Xia earned her B.S. (1999) in Chemistry from Lanzhou University, China, M.S.
(2002) from Shanghai Institute of Material Medical, CASs, China, and Ph.D. (2006)
under the supervision of Professor Scott A. McLuckey from Purdue University, USA.
After postdoctoral training with Prof. Graham R. Cooks at Purdue, Dr. Xia took positions
as Assistant Professor and Associate Professor at the Department of Chemistry, Purdue
University. She is currently a Professor at the Department of Chemistry, Tsinghua
University, Beijing, China. Dr. Xia utilizes radical reactions as a unique approach to
achieve enhanced bioanalysis via mass spectrometry. In particular, her recent research emphasizes on
developing lipidomic tools capable of resolving structural isomers. Her work has resulted in over 90 peer-
reviewed publications and book chapters. Dr. Xia received ASMS Research Award (2013) and served as
Secretary of ASMS from 2015-2017. She is currently on the editorial board of the Journal of the American
Society of Mass Spectrometry.
Representative Publications:
1. X. Zhao, W. Zhang, D. Zhang, X. Liu, W. Cao, Q. Chen, Z. Ouyang, Y. Xia * , “A Lipidomic
Workflow Capable of Resolving sn- and C=C Location Isomers of Phosphatidylcholines”, Chem.
Sci., 2019, 10, 10740-10748
2. X. Xie, Y. Xia* “Analysis of Conjugated Fatty Acid Isomers by the Paternò-Büchi Reaction and
Trapped Ion Mobility Mass Spectrometry”, Anal. Chem. 2019, 91, 7173-7180.
3. W. Zhang, D. Zhang, Q. Chen, J. Wu, Z. Ouyang*, Y. Xia* “Online photochemical derivatization
enables comprehensive mass spectrometric analysis of unsaturated phospholipid isomers” Nat.
Commun., 2019, 10, 79-07963
4. X. Ma, L. Chong, R. Tian, R. Shi, T. Y. Hu, Z. Ouyang*, Y. Xia*, “Identification and quantitation
of lipid C=C location isomers: a shotgun lipidomics approach enabled by photochemical reaction”,
Proc. Natl. Acad. Sci. USA, 2016, 113, 2573-2578.
5. X. Ma and Y. Xia*, “Pinpointing Double Bonds in Lipids by Paternò–Büchi Reactions and Mass
Spectrometry”, Angew. Chem., Int. Ed , 2014, 53, 2592-2596.
Join the FeMS network (Females in Mass Spectrometry) for a presentation from special guest Dr. Yu Xia including time for discussion and a breakout networking session. This is a fun, informal way to stay connected and meet people in the field.
Perspectives on Future LC-MS/MS Developments for the Routine Clinical Lab, with Special Focus on 25-OH Vitamin D Testing
Lorin Bachmann, PhD, DABCC
VCU Health System
Lorin Bachmann joined the VCU Department of Pathology in 2007. She currently serves as Co-Director of Clinical Chemistry, Co-Director of Point-of-Care Testing, Director of the New Kent Emergency Department Laboratory, Technical Advisor for the Operating Room Laboratory, Pathology Outreach and Clinical Trials, and Laboratory Director for multiple VCUHS outreach laboratories. Dr. Bachmann received her PhD in Molecular Medicine from the University of Virginia, followed by a fellowship in clinical chemistry and proteomics research at the University of Virginia. Dr. Bachmann is certified by the American Board of Clinical Chemistry.
Dr. Bachmann serves as the Past Chair of the Chemistry and Toxicology Expert Panel for the Clinical Laboratory and Standards Institute (CLSI) and as a member of the CLSI Board of Directors. She also serves as a member of the College of American Pathologists Accuracy Based Programs Committe.
Dr. Bachmann’s research interests include evaluation and validation of new clinical laboratory assays, clinical laboratory analyzer design, development of mass spectrometry-based assays for the clinical laboratory and standardization of laboratory testing. She serves as a Member of the National Kidney Disease Education Program (NKDEP)/International Federation of Clinical Chemistry Laboratory (IFCC) Joint Lab Working Group, whose goal is to accomplish standardization of urine albumin methods to enable utility of clinical decision thresholds.
Dr. Bachmann has received numerous awards for her contributions to professional societies, education and research. She serves as principal investigator for multiple industry-sponsored studies.
Accurate 25-OH Vitamin D measurements are important for assessment and management of patients with hypovitaminosis D. LC-MS/MS measurement procedures are more selective than immunoassay measurement procedures for 25-OH Vitamin D and generally exhibit improved recovery of 25-OH Vitamin D2. However, challenges related to increased labor requirements for preanalytical processing, additional method validation requirements for LDTs and lack of complete automation of quality assurance monitoring have presented significant barriers for implementation of LC-MS/MS in the routine clinical laboratory. Hear from a clinical laboratory and LC-MS/MS expert about the quality assurance needs of the routine clinical laboratory, the challenges associated with managing laboratory developed tests (LDTs) and the perspectives on future LC-MS/MS developments.
*Thermo Fisher Scientific products are distributed globally so uses, applications, and availability of product in each country depend on local regulatory marketing authorization status.
Clifton Fagerquist, PhD USDA-ARS Produce Safety and Microbiology Research
The State of the DART: Does Direct Analysis in Real-Time Mass Spectrometry have a Future in Clinical Chemistry?
Chip Cody, PhD
JEOL, USA, Inc.
Dr. Robert B. (Chip) Cody received his Ph.D. from Purdue University in 1982 under the direction of Prof. Ben S, Freiser. After graduate school, he worked at Nicolet Instruments developing methods for Fourier Transform Mass Spectrometry until 1989 when he joined JEOL USA, Inc. where he is presently Product Manager for Mass Spectrometry. Among other achievements, Dr. Cody is responsible for developing the trapped-ion tandem-in-time MS/MS and MSn techniques, laser-desorption FTICR, and is coinventor of the DART ion source. He served as Vice-President for Arrangements for the American Society of Mass Spectrometry and was awarded the 2011 Anachem Award and a 2012 Purdue University Distinguished Alumni Award. He has over 100 publications and several patents, edited (with Marek Domin of Boston College) the book Ambient Ionization Mass Spectrometry, and is author of the Mass Mountaineer software suite.
It has now been 17 years since a patent was filed describing the Direct Analysis in Real Time (DART) ion source, yet no clinical applications of DART MS are currently in use. This is not to say that DART has no potential for clinical applications! As an ambient ionization method, DART has several attractive characteristics for clinical chemistry. DART analysis is rapid and robust, and can be applied to a wide range of analytes. In combination with a high-resolution and/or tandem mass spectrometer, DART can be quite sensitive and selective. Point-of-care applications are possible if DART is combined with a compact mass spectrometer.
Several promising DART applications have been reported. Because it produces a broad profile of small-molecule biomarkers, DART is well matched with chemometric analysis for speciation and classification. Two published feasibility studies have shown the potential for microbial identification using DART MS. The first (from CDC and GA Tech) used in-situ methylation and DART to identify bacterial fatty acid profiles. The second study found that free fatty acids from a simple extraction method could identify ten different pathogens. Another study from the Fernandez lab at GA Tech showed a DART method for ovarian cancer screening with statistics that showed 100% accuracy!
Clinical toxicology is another area of potential application. DART is well established for forensic drug screening. That same capability could be used to screen for drugs and toxins to guide treatment in victims of poisoning or overdose. With relatively simple sample handling methods, detection limits for drugs in body fluids are suitable for rapid screening. DART has demonstrated the potential for monitoring drug excretion kinetics and in at least one case, detection of biomarkers for disease conditions. In a recent study, we have found that DART can be combined with another ambient ionization method (Coated Blade Spray) to provide complementary data from minimal sample volumes.
So, why has DART not yet found a place in clinical chemistry? Commercially available laboratory systems have been on the market for 15 years, and portable systems are also now commercially available. Perhaps the answer is just a need for early adopters who are willing to carry out clinical validation studies, much as the VA DFS did for forensic drug screening.
Grace van der Gugten, B.Sc. Chemistry Alberta Precision Laboratories
Deborah French, PhD, DABCC (CC, TC) UCSF
Taking Aim at Analytical Interference in LC-MS Without Shooting Yourself in the Foot
Zlata Clark, PhD
B.S. in Analytical Chemistry, Masaryk University, Brno, Czech Republic.
Ph.D. in Bioanalytical Chemistry, Brigham Young University, Provo, Utah.
Nearly three decades of HPLC, CE, CE-MS, and LC-MSMS method development and validation experience in academic, pharmaceutical, and clinical laboratory environments.
Introduction
The popularity of LC-MS/MS-based methods for clinical testing continues to rise. However, despite their superior analytical specificity, these methods may still suffer from interference affecting method accuracy and precision, and hence negatively impacting patient care.
The aim of this Practical Training Track session is to introduce the participant to the following:
Segment #1
After each respective segment, attendees should be able to:
Segment #1
1.List sources of guidelines for interference testing
2.Define analytical interference and identify its various sources
Segment #2
1.Describe the different types of experiments used for interference testing in LC-MS/MS
2.Explain why waiting until validation to test for interference is not be desirable
Segment #3
1.Discuss the role of internal standard in mitigating interference
2.Name parameters used for interference monitoring
Stephen Master, MD, PhD, FADLM Children's Hospital of Philadelphia
MCR and VCA
Dr. Andrea Geistanger
Roche Diagnostics GmbH
Andrea Geistanger is Head of MassSpec Biostatistics, at Roche Diagnostics in Germany. Her department of biostatisticians supports system and assay development through the whole life cycle of Roche’s cobas products. Her team is involved in the early development phases, including biomarker search projects with machine learning and multivariate statistics analysis. During product development phases, Andrea’s data analysts support scientists in experimental planning with Design of experiments, as well as in the experiment of validation studies according to regulatory requirements. Furthermore, they develop standardization schemes and calibration concepts for cobas analyzers. Throughout the development phase, software tools are designed and developed as needed. These programs are also made available to a broader community through open software projects.
Andrea Geistanger recently gave a talk at MSACL Connect on the mcr and VCA R packages for method comparison and precision analysis. That talk was dedicated to statistical tools, the actual one will address the soft topics of these experiments, as study design, analysis and interpretation.
Trueness and precision are the key quality attributes of a diagnostic assay and have to be proven in validation experiments throughout each assay development. CLSI does also acknowledge the importance of these criteria, having two guidelines in place, EP9 for method comparison, and EP5 for precision studies describing the design and the analysis of the corresponding experiments. The statistical methodology for both experiments is quite advanced and cannot be operated in a bread and butter software such as Excel. For method comparison studies a Deming regression is required and in some cases also a robust Passing-Bablok regression is state-of-the-art. Classical linear regression methods are not appropriate here, as measurement errors occur for both measurement methods. For precision studies, an appropriate variance-components design should be used and statistically analyzed accordingly.
The mcr R-package is a free available open source R package, which incorporates all analysis methods for method comparison studies, with special focus on the regression methods as Deming or Passing-Bablok regression.
The VCA package is the pendant for precision experiments, where different measurement designs can be analyzed. It is also freely available as open source R-package. Both R packages have been developed and are maintained by the Roche Diagnostics R&D biostatistics department.
The talk will cover the major aspects of the analysis requirements for method comparison and variance-components studies. In addition, we show the features of both R packages, their calculation capabilities as well as the graphical representation possibilities.
Jessica Lukowski, PhD Pacific Northwest National Laboratory
The Chemical Characterization of the Cells in the Brain Using Mass Spectrometry
Jonathan Sweedler, PhD
University of Illinois at Urbana Champaign
Jonathan Sweedler is the James R. Eiszner Family Endowed Chair in Chemistry, the Director of the School of Chemical Sciences, and has appointments in Neuroscience, Molecular and Integrative Physiology, Bioengineering and Medicine. His research interests focus on developing new approaches for assaying small volume samples, and in applying these methods to study novel interactions between cells. These analytical approaches include capillary separations, single cell mass spectrometry and mass spectrometry imaging. He has used these tools to characterize small molecules and peptides in a range of animal models across the metazoan and in samples as small as individual cells and cellular domains. Sweedler has published more than 500 manuscripts and presented 500 invited lectures. He is currently the Editor-in-Chief for Analytical Chemistry.
In the postgenomic era, one expects the suite of chemical players in a brain region to be known and their functions uncovered. Perhaps surprisingly, many neurochemicals remain poorly characterized and for those that are known, their localization, dynamics and function are oftentimes unknown. Mass spectrometry imaging (MSI) and single cell measurements using spatially targeted MS are highlighted. Using these approaches, we can measure lipids, fatty acids, neurotransmitters and neuropeptides, among others. For single cell measurements, the cells of interest are scattered across a microscope slide, the exact cell positions determined via optical microscopy, and mass spectra are acquired only at the cell positions. The single cell assays allow differences in the metabolome and peptidome from supposedly homogeneous populations of cells to be explored. By obtaining information from tens of thousands of individual cells, rare cells are found and unusual neurochemicals are discovered. Machine learning based approaches are highlighted to extract details on differences between targeted cellular populations.
While MS is one of the most information rich chemical characterization approaches, additional complementary information ranging including immunohistochemistry and vibrational spectroscopy aids in identifying cell types and in determining optimum follow-up studies. For select cells, follow-up capillary electrophoresis-mass spectrometry also is performed. Several applications of MSI and single cell mass spectrometry are highlighted from the discovery of unusual metabolites to characterizing the both known and previously unknown neuropeptides and hormones. Our overarching goal is to uncover the complex chemical mosaic of the brain and pinpoint key cellular players involved in a range of physiological and pathological processes.
Richard Drake, PhD Medical University of South Carolina
Mapping the Chemical Space of Biological Systems via MALDI Mass Spectrometric Imaging and in situ Molecular Analysis
Lingjun Li, PhD
School of Pharmacy and Department of Chemistry, University of Wisconsin - Madison
Lingjun Li is a Vilas Distinguished Achievement Professor and the Charles Melbourne Johnson Distinguished Chair Professor of Pharmaceutical Sciences and Chemistry at the University of Wisconsin-Madison (UW-Madison). Dr. Li received her B.E. degree in Environmental Analytical Chemistry from Beijing University of Technology, China and her Ph.D. degree in Analytical Chemistry/Biomolecular Chemistry from the University of Illinois at Urbana-Champaign (UIUC). She did three-way postdoctoral research at the Pacific Northwest National Laboratory, Brandeis University, and UIUC before joining the faculty at UW-Madison in December 2002. Her research interests are in analytical neurochemistry, neuroproteomics and biological mass spectrometry. Dr. Li published more than 300 papers and has given over 200 invited talks. She was the recipient of the ASMS Research Award, NSF CAREER Award, Sloan Fellowship, PittCon Achievement Award, and ASMS Biemann Medal, and was named one of the Top 50 most influential women in the analytical sciences and featured in the 2019 and 2021 Top 100 Power List by the Analytical Scientist. Dr. Li is currently an Associate Editor for the Journal of the American Society for Mass Spectrometry (JASMS) and served on the Board of Directors for the US HUPO.
Mass spectrometric imaging (MSI) provides an attractive opportunity to detect and probe the molecular content of tissues in an anatomical context. This technique creates distribution maps of select compounds without the need for priori knowledge of target analytes. In this presentation, I will describe our efforts and recent progress in mapping and imaging of a wide variety of signaling molecules in several biological systems, highlighting the unique challenges and important roles of MSI in the areas of proteomics, peptidomics, and metabolomics.
Although high resolution accurate mass (HRAM) MSI platform offers unique advantages for mapping small molecule metabolites due to its high resolution and accuracy measurement, typical MALDI-LTQ-Orbitrap platform suffers from limited utility for large peptide and protein analysis due to its maximum m/z 4000. To overcome this challenge, we employed volatile matrices to produce multiply charged ions in MALDI source via laserspray ionization (LSI) and matrix assisted ionization in vacuum (MAIV) techniques on the MALDI Orbitrap platform. These new ionization techniques enabled substantial expansion of the mass range of the instrument and generated improved fragmentation efficiency compared to traditional MALDI-MS. To further enhance the chemical information extracted from in situ MALDI MSI experiments, we report on a multiplex-MSI method, which combines HRAM MSI technology with data dependent acquisition (DDA) tandem MS analysis in a single experiment. To improve the dynamic range and efficiency of in situ DDA, we introduce a novel gas-phase fractionation strategy prior to MS/MS scans, to decrease molecular complexity of tissue samples for enhanced peptidome coverage. In addition, the application of HRAM MALDI MSI to lipid analysis in a restenosis rat model and the utility of a novel subatmospheric pressure (SubAP)/MALDI source coupled with a Q Exactive HF hybrid quadrupole-orbitrap mass spectrometer for in situ imaging of glycans from formalin-fixed paraffin-embedded (FFPE) tissue sections and its translation to clinical cancer tissue microarray analysis will be highlighted. Finally, to further improve the sensitivity of MALDI MSI, a photoactive compound, 2-nitrobenzaldehyde is used to initiate a nanosecond photochemical reaction (nsPCR). This nsPCR strategy enables enhanced neuropeptide identification and visualization from complex tissue samples through on-demand removal of surrounding matrices within nanoseconds. The utility of this new approach for in situ analysis of endogenous biomolecules is evaluated and demonstrated.
Grace van der Gugten, B.Sc. Chemistry Alberta Precision Laboratories
No Middleware? No Problem. Using R and Shiny for Routine Review of QC Data and Other Quality Metrics
Dennis Orton, PhD, FCACB
Alberta Precision Labs University of Calgary
I graduated with a PhD from Dalhousie University in Halifax, NS, Canada in 2014 where I worked on developing and applying quantitative proteomics workflows for biomarker discovery. I then completed a Clinical Biochemistry Fellowship in Calgary, AB, Canada in 2016 before moving on to work as a Clinical Biochemist in the Fraser Health region in British Columbia, Canada. During this time I gained significant experience in using R and RStudio, writing numerous shiny apps to perform QC management and to streamline LC-MS/MS data workflows. In 2019, I moved to my current position in Calgary where I head the Mass Spectrometry testing facility for Alberta Precision Laboratories. Primarily focussed on toxicology testing, I have overseen a transition towards more endocrine testing and eliminated low-throughput GC-MS workflows in favour of targeted, MRM based LC-MS analyses. My research is focused on promoting LC-MS technologies and development of tools and workflows to bring targeted proteomics methodologies to routine clinical application.
Introduction: Review of quality control (QC) data in the clinical lab generally utilizes vendor-specific and costly middleware systems which may not be user friendly or display all desired information. Additionally, many instruments may not come with a middleware option, the middleware may be cost-prohibitive, or it may not allow off-site data review, making routine QC review fairly labour intensive or time-consuming. These issues are especially problematic in regions with de-centralized clinical testing networks or with multiple analyzer vendors, and review of QC data is often limited to rudimentary Laboratory Information System (LIS) functionality, which is generally not user friendly or intuitive to use.
Objectives: Design a user interface to allow streamlined QC data review and allow rapid multi-site and/or multi-analyzer QC comparisons using R.
Methods: This script employs R (version 3.6.1) and RStudio (version 1.2.1335) with packages shinydashboard, ggplot2, and tidyverse to visualize QC data with filters for date range, assay type, QC product, analyzer, and QC lot number. The data is obtained from an automated download containing all QC data in the LIS over a 24 hour period with a sample identifier, test name, verified date, analyzer result, expected mean and standard deviation, QC product as well as the QC lot number. The data is saved to a shared network drive with access restricted to regional supervisory and technical staff.
The R script is set to automatically import the previous 30 days of QC data and displays the running mean and standard deviation for each test using the applied filters. Using shinydashboard format, more or less data can be viewed by importing more data files or by applying date range filters. Optional filters include test name, analyzer name/type, and QC material, which allow users to assess assay performance down to the instrument level. Multiple tabs are provided to display data in tabular or graphical format, with options for data to be summarize by day, week, or month.
Results: This dashboard provides a method for streamlining QC data review from various analyzer types and vendors, across sites and lot numbers, all of which can be viewed remotely. This provides technical staff the opportunity to quickly get through monthly QC review, as well as identify analyzers which may be seeing shifts in QC running means between analyzers or lot numbers. Ready access to this data allows staff to get through routine QC review quickly, while also promoting better region-wide lab quality and inter-site continuity. Adaptation of this dashboard could also allow review of other quality metrics such as patient running means or hemolysis rates, provided this data is captured in the LIS and access to the raw data is available.
Conclusion: This is a simple, customizable tool that is able to compile QC data for review without the need for investment in expensive or complicated middleware products.
Klára Ščupáková Maastricht MultiModal Molecular Imaging Institute (M4I), Maastricht University
Components of Reproducible Quantitative Mass Spectrometry-based Proteomics: A Statistician
Olga Vitek, PhD
Northeastern University, Khoury College of Computer Sciences
Olga Vitek is a professor at Northeastern University. She joined Northeastern in the summer of 2014 with a joint appointment in the College of Science and the Khoury College of Computer Sciences. She was previously named the Sy and Laurie Sternberg Interdisciplinary Associate Professor at Northeastern University.
Prior to joining Northeastern, she was an assistant professor and then a tenured associate professor at Purdue University, with a joint appointment in the Department of Statistics and Department of Computer Science (2006-2014). She interned at Eli Lilly & Company in Indianapolis and held a position of post-doctoral associate in the Aebersold Lab at the Institute for Systems Biology in Seattle.
Vitek’s work develops statistical and computational methods for systems-wide molecular investigations of biological organisms. Her group works with high-throughput large-scale investigations in quantitative genomics, proteomics, metabolomics and ionomics. This research relies on mass spectrometry and other complementary technologies to characterize the components of the biological systems, their functional interactions, and their relevance to disease.The goal of Vitek’s research is to provide statistical and computational methods and open-source software for design of these experiments, and for accurate and objective interpretation of the resulting large and complex datasets.
Vitek is a recipient of the National Science Foundation CAREER Award. During her time at Purdue University, she was a University Faculty Scholar, as well as recognized with an Outstanding Assistant Professor Teaching Award, a Graduate Student Mentoring Award, and a Teaching for Tomorrow Award. She serves on the board of directors of the U.S. Human Proteome Organization.
Quantitative mass spectrometry-based proteomics aims to distinguish systematic variation in protein abundance (due, e.g., to a treatment or a disease) from nuisance biological and technological variation. Statistical mindset is key for doing so in both repeatable and reproducible manner. Frequently, statistical tasks are viewed as limited to detecting differentially abundant proteins. In reality, statistical components of reproducibility are substantially broader. They include all aspects of data processing (Which features should we use to quantify a protein? How should we combine the features into a protein-level conclusion?). They also include aspects of experimental design, from both biological perspective (Which proteins and samples, and how many, do we need to quantify?) and technological perspective (Are the assays appropriate for the task? Do the experimental steps run properly?). Answering these questions requires the availability of statistical methods, and but also of publicly available data that help understand the advantages and the limitations of the methodological choices. This talk will highlight the contributions of our lab to these components of reproducible research.
Brain Organoids as a Model System for Human Neurodevelopment and Evolution
Alysson Muotri, PhD
University of California, San Diego
Dr. Muotri earned a BSc in Biological Sciences from the State University of Campinas in 1995 and a Ph.D. in Genetics in 2001 from University of Sao Paulo, in Brazil. He moved to the Salk Institute as Pew Latin America Fellow in 2002 for a postdoctoral training in the fields of neuroscience and stem cell biology. He has been a Professor at the School of Medicine, University of California in San Diego since late 2008. His research focuses on modeling neurological diseases, such as Autism Spectrum Disorders, using human induced pluripotent stem cells and brain organoids. He has received several awards, including the prestigious NIH Director’s New Innovator Award, NARSAD, Rock Star of Innovation from CONNECT, NIH EUREKA Award among others.
Structural and transcriptional changes during early brain maturation follow fixed developmental programs defined by genetics. However, whether this is true for functional network activity remains unknown, primarily due to experimental inaccessibility of the initial stages of the living human brain. We developed cortical organoids that spontaneously display periodic and regular oscillatory network events that are dependent on glutamatergic and GABAergic signaling. These nested oscillations exhibit cross-frequency coupling, proposed to coordinate neuronal computation and communication. As evidence of potential network maturation, oscillatory activity subsequently transitioned to more spatiotemporally irregular patterns, capturing features observed in preterm human electroencephalography (EEG). These results show that the development of structured network activity in the human neocortex may follow stable genetic programming, even in the absence of external or subcortical inputs. Our approach provides novel opportunities for investigating and manipulating the role of network activity in the developing human cortex. Applications for neurodevelopmental disorders and brain evolution will be discussed.
Anne K. Bendt, PhD Singapore Lipidomics Incubator (SLING), National University of Singapore
Grace van der Gugten, B.Sc. Chemistry Alberta Precision Laboratories
Externally hosted activity.
FeMS Happy Hour with guest Inese Lowenstein
Inese Lowenstein, MBA
SCIEX
As President of SCIEX, Inese Lowenstein is responsible for SCIEX’s global operations and leading the company as it continues providing innovative solutions that enable our customers to get to life-changing answers faster, advancing scientific understanding and safeguarding health.
Inese has more than 25 years of experience in Sales, Marketing, Product Management and General Management. Most recently, she was Senior Global Vice President, Sales & Service, SCIEX, where she was responsible for leading a direct and distributed team of sales, technical and customer support, and market development and service professionals globally, to drive profitable revenue growth. She also had responsibility for Global Digital Marketing and Commercial Operations.
Prior to this, Inese spent more than 13 years with EMD Millipore and Merck KGaA, Darmstadt, Germany, in roles of increasing responsibility culminating in the role of Executive Vice President, Head of Display Materials Business Unit, Performance Materials, where she was responsible for managing the commercial and R&D functions for a 1.5 billion EUR business with 99 percent of revenues originating in Asia.
Inese holds a Bachelor of Engineering Science with major in Economics & Engineering from Riga Technical University, Riga, Latvia and a Master of Business Administration from Walter A. Haas School of Business, University of California at Berkeley.
Join the FeMS network (Females in Mass Spectrometry) for a presentation from special guest Inese Lowenstein including time for discussion and a breakout networking session. This is a fun, informal way to stay connected and meet people in the field.
Comprehensive Enumeration of Infiltrating Immune Cells in Triple Negative Breast Cancer
Michael Angelo, MD, PhD
Stanford University School of Medicine
Michael Angelo, MD PhD is a board-certified pathologist in the department of Pathology at Stanford University School of Medicine. Dr. Angelo is a leader in high-dimensional imaging with expertise in tissue homeostasis, tumor immunology, and infectious disease. His lab has pioneered the construction and development of Multiplexed Ion Beam Imaging by time of flight (MIBI-TOF). MIBI-TOF uses secondary ion mass spectrometry and metal-tagged antibodies to achieve rapid, simultaneous imaging of dozens of proteins at subcellular resolution. His lab used this technology to discover previously unknown rule sets governing the spatial organization and cellular composition of immune and stromal cells within the tumor microenvironment in triple-negative breast cancer and ductal carcinoma in situ. This effort has led to ongoing work aimed to define broader structural mechanisms that promote tolerogenic niches in cancer, tuberculosis, and the maternal-fetal interface. His lab is expanding this spatial biology framework to leverage new technologies that can map the spatial distribution of transcripts, lipids, and glycans. Dr. Angelo is the recipient of 2014 NIH Director’s Early Independence, 2020 DOD Era of Hope Award and is a principal investigator on multiple extramural awards from the National Cancer Institute, Breast Cancer Research Foundation, Parker Institute for Cancer Immunotherapy, the Bill and Melinda Gates Foundation, and steering committee co-director of the Human Biomolecular Atlas (HuBMAP) initiative.
Adam Rosebrock, PhD Stony Brook School of Medicine
Spatial Metabolomics: From Big Data to Single Cells
Theodore Alexandrov, PhD
European Molecular Biology Laboratory (EMBL) Heidelberg
Theodore Alexandrov is a group leader at the European Molecular Biology Laboratory (EMBL) in Heidelberg, the head of the EMBL Metabolomics Core Facility and an Assistant Adjunct Professor at the Skaggs School of Pharmacy, University of California San Diego. The Alexandrov team at EMBL aims to reveal secrets of metabolism in time and space in tissues and single cells by developing experimental and computational methods. The team unites interdisciplinary scientists from biology, chemistry, and computer science as well as software and machine learning engineers. Theodore Alexandrov is a grantee of an ERC Consolidator project focused on studying metabolism in single cells, as well as of various other European, national, NIH, and industrially-funded projects. He has co-founded and scientifically directed the company SCiLS and has over 70 journal publications and patents in spatial omics.
PhD 2007, St. Petersburg State University, Russia
Postdoctoral research at the University of Bremen, Germany
Group leader, University of Bremen, Germany
Assistant Adjunct Professor, University of California San Diego, USA
Team leader at EMBL since 2014.
Recent discoveries put metabolism into the spotlight. Metabolism not only fuels cells but also plays key roles in health and disease in particular in cancer, inflammation, and immunity. In parallel, emerging single-cell technologies opened a new world of heterogeneous cell types and states previously hidden beneath population averages. Yet, methods for discovering links between metabolism, cell states, metabolic plasticity and reprogramming on the single-cell level and in situ are crucially lacking. Our research aims to bridge this gap. First, I will explain how the emerging technology of imaging mass spectrometry can be used for the spatial profiling of metabolites, lipids, and drugs in tissues. I will present our cloud and Artificial Intelligence-powered platform METASPACE which is increasingly used across the world. In the second part of my talk I will focus on our method SpaceM for spatial single-cell metabolomics in situ. We applied SpaceM to investigate hepatocytes stimulated with fatty acids and cytokines, a model mimicking the inflammation-associated transition from the fatty liver disease NAFLD to steatohepatitis NASH. We characterized the metabolic state of steatotic hepatocytes and metabolic plasticity associated with the inflammation. We discovered that steatosis and proliferation take place in distinct cell subpopulations, each with a characteristic spatial organization and metabolic signatures. Overall, such methods open novel avenues for understanding metabolism in tissues and cell cultures on the single-cell level.
Free Trial then $47 donation to COVID-19 charities through May
Externally hosted activity.
Ace the Deck
Karen Mahooti, MBA
Articulate Consulting
Karen holds an MBA from the Yale University School of Management and is founder and principal at Articulate Consulting. Karen has provided training in presentation development skills to professionals around the world from executives and managers to analysts, consultants, and graduate students. In addition, over her career as both a management consultant and a marketing professional for a Fortune 20 company, Karen has created a multitude of clear and compelling presentations to help senior executives and board members of large companies make better strategic decisions. She understands first-hand the challenges of creating presentations when the stakes are high and clients' expectations are even higher. Karen's style is both visionary and practical. She seeks to inspire others to have confidence in what they can accomplish with their presentations, and also to give them the concrete know-how and tools they need to immediately begin creating presentations that give them the influence they desire.
Karen Mahooti is a repeat instructor at MSACL US where she has received excellent feedback for her 2 day short courses that train attendees how to effectively present their science - such an important skill! Karen developed an online version of her course to bring all the goodness to a larger audience. Additionally, for the month of May, Karen is running a fundraiser for charities - you get the course at a very affordable price and aid the crisis response in the process.
Do not pass up this opportunity!
Cheers
-Amber
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Give hope and boost your storyboarding skills at the same time. Through the end of May, the online version of Karen's highly-rated Ace the Deck course is discounted to $47 (from $297), and 100% of the profits will go to three charities helping in the global COVID-19 crisis: Save the Children (savethechildren.org), Convoy of Hope (convoyofhope.org) and The Charis Project (thecharisproject.org).
Enter Coupon Code GIVEHOPE at Checkout
Why complete this course?
Ace the Deck walks you through a proven, step-by-step process for building compelling, professional presentations. At the end you will know EXACTLY what to do first, second, third and be able to start right away with ALL THREE components you need:
Detection of alcohol use/exposure in multiple biological matrices by LC-MS/MS
Gwen McMillin, PhD
University of Utah and ARUP
Dr. McMillin is a Professor (Clinical) at the University of Utah in the Department of Pathology and a Medical Director for Clinical Toxicology, Mass Spectrometry and Pharmacogenomics at ARUP Laboratories. She received her Ph.D. in Pharmacology and postdoctoral training in clinical chemistry from the University of Utah. Dr. McMillin is board certified by the American Board of Clinical Chemistry in Clinical Chemistry and Toxicological Chemistry. She also currently serves as a member of the Executive Board for the ARUP Institute of Clinical and Experimental Pathology and is actively involved in several external Professional Organizations.
Kamisha Johnson-Davis, PhD
University of Utah and ARUP
Dr. Johnson-Davis is an Associate Professor (Clinical) at the University of Utah in the Department of Pathology and a Medical Director for Clinical Toxicology at ARUP Laboratories. She received her B.S. degree in Biochemistry from the University of California, Riverside and her Ph.D. in Pharmacology from the University of Utah. She was a postdoctoral research associate at the Center for Human Toxicology and she completed a postdoctoral fellowship in clinical chemistry at the University of Utah, Department of Pathology. Dr. Johnson-Davis is board certified by the American Board of Clinical Chemistry in Clinical Chemistry in Clinical Chemistry and Toxicological Chemistry and she is the Director for the Clinical Chemistry Fellowship Program at the University of Utah.
Alcohol use is widespread, and when used in excess, is associated with many negative health and social consequences. As such, detection of alcohol use/exposure is relevant to many clinical scenarios such as substance use disorder clinics, surgery qualification, chronic pain management and pregnancy. In this webinar we will provide an overview of the biomarkers commonly used to detect and monitor alcohol exposure. We will also describe approaches and limitations to detecting and measuring concentrations of alcohol metabolites in urine, whole blood, meconium and umbilical cord tissue by LC-MS/MS.
Mass Spectrometry: Is it Taking the Pain Out of Pain Management
Paul Jannetto, Ph.D., DABCC, FAACC, M.T.(ASCP)
Mayo Clinic
Paul J. Jannetto, Ph.D., DABCC, FAACC, M.T.(ASCP), is an Associate Professor in the Department of Laboratory Medicine and Pathology and a Consultant at the Mayo Clinic (Rochester, MN), where he serves as the Co-Director for the Clinical Mass Spectrometry Laboratory, Clinical and Forensic Toxicology Laboratory and the Metals Laboratory. Previously, he was an Associate Professor of Pathology at the Medical College of Wisconsin (Milwaukee, WI) where he functioned as the Director of Clinical Chemistry/Toxicology at Dynacare Laboratories (Milwaukee, WI). He earned his BS in Clinical Laboratory Science from the University of Wisconsin-Milwaukee and worked five years as a Medical Technologist for Medical Science Laboratories before entering graduate school. He then earned a Ph.D. in Pharmacology and Toxicology at the Medical College of Wisconsin. He is board-certified by the American Board of Clinical Chemistry and American Society for Clinical Pathology. His clinical and scientific interests are centered on Clinical & Forensic Toxicology, Therapeutic Drug Monitoring, and Elemental Analysis.
Dr. Jannetto has been actively involved in the American Association for Clinical Chemistry (AACC) where he has participated in the TDM/Toxicology, Mass Spectrometry and Separation Sciences, Molecular Pathology, Management Sciences and Patient Safety, Personalized Medicine, and Critical and POCT divisions. In the past, he has served on numerous positions at the local level in both the Chicago and Midwest sections (e.g. Chair of the Chicago Section, Secretary of the Chicago Section, and Treasurer of the Midwest Section of AACC), and at the national level as a member of the Governance Review Advisory Taskforce, NACB Board of Directors, AACC Board of Directors, and Chair of the House of Delegates. Dr. Jannetto is also a member of the American Academy of Pain Medicine, International Association of Therapeutic Drug Monitoring and Clinical Toxicology, and was the President of the Midwest Association for Toxicology and Therapeutic Drug Monitoring. He has over 50 peer-reviewed publications, 14 book chapters, and over 75 abstracts/presentations at various national meetings.
Sarah Delaney, MSc, PhD
Mayo Clinic
Sarah Delaney, MSc, PhD, is a second year Clinical Chemistry Fellow at Mayo Clinic (Rochester, MN) currently serving as an Acting Director in the Clinical and Forensic Toxicology Laboratory. She completed both her MSc and PhD in the Department of Pharmacology and Toxicology at the University of Toronto. Before entering her PhD program, Sarah was active in the clinical chemistry community in her role as the clinical project coordinator for the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) study at SickKids Hospital in Toronto. Her scientific interests include drug monitoring in pain management patients and neonatal/pediatric laboratory medicine.
Pain is one of the most common reasons people seek care and affects more Americans than diabetes, heart disease and cancer combined. Treatment is subjective as pharmacological interventions using opiates and opioids involve empirical adjustments based upon observed clinical outcomes including the presence of adverse drug reactions. Addiction and diversion of pain management medications is also a growing problem and a key concern for clinicians. Therefore, professional organizations and published recommendations include the use of laboratory tests, specifically urine drug testing. As a result, physicians are using a variety of urine drug tests to provide objective measures to effectively manage pain patients, assess compliance, and detect diversion. This session will focus on the use of mass spectrometry-based urine tests and discuss the advantages and limitations of these assays.
Following this session the participants will be able to:
Describe the advantages and challenges of mass spectrometry-based testing for pain management patients.
Successfully overcome some of the challenges associated with mass spectrometry-based urine drug testing for pain management patients
List some future opportunities for mass spectrometry-based pain management testing.
Expected Outcomes:
Detailed understanding of the advantages and challenges of mass spectrometry-based urine drug testing for pain management patients.
Needs Assessment:
Urine drug testing is recommended by multiple clinical practice guidelines for use in the management of pain patients. Due to the lack of standardized laboratory test offerings, methodologies, and reporting formats coupled with incomplete knowledge surrounding the limitations of each type of laboratory test, incorrect interpretation by clinicians is possible. This webinar will discuss the strengths and limitations of using mass spectrometry-based testing for compliance monitoring of pain management patients. It will also discuss various strategies to overcome some of the challenges and future opportunities.
Metrological Traceability of Lp(a) Requires Defining the Measurand and Introducing Molar Units
Christa Cobbaert, PhD
LUMC
Christa Cobbaert is a Laboratory Specialist in Clinical Chemistry and Laboratory Medicine and heads the Department of Clinical Chemistry and Laboratory Medicine at LUMC, Leiden.
She is vice-chair of the International Federation of Clinical Chemistry Scientific Division Executive Committee and chair of the European Federation of Laboratory Medicine Working Group on Test Evaluation . She is an expert in metrology, i.e. the science of measurement, which is essential for global standardization c.q. harmonization of medical tests.
Introduction
Lipoprotein(a) (Lp(a)) is a lipoprotein particle that is causally related with atherosclerotic disease, myocardial infarction and aortic valve stenosis. The recent introduction of Lp(a) lowering medication has caused large interest in Lp(a) quantitation. The Lp(a) particle consists of an LDL particle to which an apolipoprotein (a) (apo(a)) protein is covalently bound via a disulfide bridge. Apo(a) contains a number of kringle IV repeats, a kringle V and a protease domain, and varies widely in size due to a size polymorphism in kringle IV-2. The Lp(a) particle holds a lipid core consisting of free cholesterol, phospholipids, cholesteryl esters and triglycerides, apoB and apo(a), and its concentration is traditionally expressed in mass units. Yet, apo(a) size heterogeneity and post-translational modifications such as N- and O-glycosylation of apo(a) affect the molecular mass of Lp(a) particles. We assessed the impact of defining the measurand at the molecular level using bottom-up proteomics, in relation to apo(a) size polymorphism and available PTMs.
Methods
The chemical composition of Lp(a) was assessed through literature study, and the masses of apoB and apo(a) were determined based on their amino acid sequence. A model for the molecular composition of Lp(a) was developed based on the assumption that the lipid composition of the particle is not affected by the apo(a) size polymorphism. The number of kringle IV-2 repeats reported in literature is 3-50, and chemical compositions were calculated for these values. Glycosylation patterns of both apoB and apo(a) were taken into account.
Results
The outcomes of the developed model correspond well with previously reported chemical compositions of Lp(a) [1,2]. An Lp(a) particle containing only three kringle IV-2 repeats per apo(a) is calculated to have a particle mass of 2,767 kDa with a lipid portion of 70% (w/w), apoB of 20% (w/w) and apo(a) of 10% (w/w). However, for a particle containing 50 kringles, the particle mass is 3,639 kDa with a lipid portion of 53% (w/w), apoB of 16% (w/w) and apo(a) of 31% (w/w). The huge mass variation of Lp(a) impedes Lp(a) standardization efforts, whereas molecular characterization of the apo(a) measurand and molar expression of apo(a) content may avert standardization problems.
Conclusions
The expression of Lp(a) particle concentrations in mass units is metrologically inappropriate and should be abandoned. Mass spectrometry using LC-MRM-MS allows molecular characterization of the apo(a) measurand and enables accurate quantitation in molar units, unaffected by the apo(a) size polymorphism and glycosylation. Future traceability of apo(a) to SI units can only be accomplished with an unequivocally molecularly defined protein measurand and the consistent use of molar units [3].
References
1. Kostner et al. J Lipid Res. 1999;40:2255-63.
2. Tsimikas et al. J Clin Lipidol. 2018;12:1313-23.
3. Cobbaert et al. Clin Chem Lab Med. 2018;56:1598-1602.
A Proposal to Standardize the Description of LC-MS-based Measurement Methods in Laboratory Medicine
Prof. Dr. med. Michael Vogeser
University Hospital, LMU Munich
Dr. Michael Vogeser, MD, is specialist in Laboratory Medicine and senior physician at the Hospital of the University of the Ludwig-Maximilians-University Munich, Germany (LMU; Institute of Laboratory Medicine). As an Associate Professor he is teaching Clinical Chemistry and Laboratory Medicine. The main scope of his scientific work is the application of mass spectrometric technologies in routine clinical laboratory testing as translational diagnostics. Besides method development in therapeutic drug monitoring and endocrinology a further particular field of his work is quality and risk management in mass spectrometry and in clinical testing in general. Michael has published >240 articles in peer reviewed medical journals. Michael heads the Commission for In Vitro Diagnostics in the German Association of Scientific Medical Societies (AWMF).)
Background: So far, most publications reporting mass spectrometry-based measurement methods intended for diagnostic use describe in detail the method realization in one individual laboratory site - showing a very limited level of abstraction
Methods: To overcome this limitation we suggest a standardized approach to reporting LC-MS based methods, differentiating between fundamental characteristics of a measurement method on the one hand; and variable characteristics on the other hand. In this concept, fundamental characteristics are those that can be essentially translated into separate realizations too - e.g. the mode of ionization (e.g., electrospray in positive polarity) or the m/z ratio of monitored ions. They are intended to define in their entirety the identity of a measurement method. In contrast, variable characteristics are those that cannot realistically be standardized over time and space
Impact of the New European In-Vitro Diagnostics Regulation for Medical Laboratories and Related Stakeholders
Folker Spitzenberger
University of Applied Sciences, Luebeck, Germany
Currently Folker is the Professor for regulatory affairs and quality management for medical devices at the University of Applied Sciences, Luebeck, Germany Drug and medical device regulatory affairs, standardization, quality management, conformity assessment, accreditation, laboratory medicine, in vitro diagnostic medical devices. His focus area of clinical/scientific work is drug and medical device regulatory affairs, standardization, quality management, conformity assessment, accreditation, laboratory medicine, in vitro diagnostic medical devices. Since 2005 until present experience as consultant, scientific expert, advisor for WHO, EU, PTB and other organizations in numerous international projects related to regulatory affairs, quality assurance, quality management, biosafety/biosecurity, accreditation/certification and standardization of medical/health laboratories.
The current regulatory rules governing in vitro diagnostic medical devices (IVDMD) in the European Union are mainly represented by the European IVD Directive dating back from 1998. This directive does not cover devices with characteristics related to newer techniques and applications in current in vitro diagnostic testing. It also lacks conformity with current international guidelines and regulation systems with regard to a number of regulatory elements such as risk-based classification of IVDMD, clinical evaluation, identification and labelling of IVDMD and handling of requirements for
Everything You Wanted to Know about Internal Standards But Were Too Afraid to Ask
Russell Grant, PhD
Labcorp
Dr. Grant earned a first-class honors degree in Industrial Chemistry from Cardiff University and a PhD in Chromatographic and Mass Spectrometric technologies from the University of Swansea, Wales, United Kingdom. He continued his scientific training in various industrial settings, which have included senior scientist at GSK, Principal scientist at Cohesive Technologies, Technical director at Eli Lilly, and Director of Mass Spectrometry at Esoterix Endocrinology. Dr Grant is currently the Vice President of Research and Development and co-discipline director for Mass spectrometry at Labcorp. Dr Grant has pioneered the use of direct injection technologies, chromatographic systems multiplexing, microsampling, utility of automation, and other new analytical platforms in direct patient care. His research goals are focused upon improvements in speed, sensitivity, and quality of liquid chromatography with tandem mass spectrometric (LC-MS/MS) analytical systems and assays. Dr Grant has been awarded 100 patents and received both the MSACL Distinguished contribution award and ASMS AL Yergey “Unsung Hero” Award in 2024 for his contributions to Clinical Diagnostics using Mass Spectrometry.
Introduction
Internal standards are ideally a perfect mimic for analytes and correct for a multitude of analytical variance and bias, when designed and used correctly. Internal standards provide qualitative details that can elucidate confidence in results release apriori, such as enabling analyte peak selection (retention time) and expected peak shape (asymmetry). Internal standards are used quantitatively to correct for inter-sample recovery variance (absolute recovery and matrix effects), as such, much credence is afforded to their performance. In our experience over >15 years, many confounding and fundamental errors in these simple premises are observed. This has led to extensive determination of absolute agreement between analytes and internal standards, with some rather surprising outcomes.
Methods
Key experimental considerations and "cause-effect" will be detailed to establish when internal standards are behaving in a manner consistent with the analyte.
Session 1 will include: What level should I add IS at? what does the IS actually do? Qualitative details and error observations, quantitative assessment of binding equivalency (Reverse admixing - and when it can be misleading), drift over time using dynamic extraction and automation tools (and how to both elucidate and correct).
Session 2 will highlight examples of internal standardization failures such as the impact of excessive labeling, Isotopic contribution (from and to analyte), and when to use an "analog" internal standard - correctly.
Session 3 will detail expanded uses of Internal standards such as in-vitro redox correction (prior to receipt in the laboratory for sample analysis), results reporting outside the calibration range and how an internal standard can be used as a calibration system (and when not to!)
Results
The end result in each of these examples is an LC-MS/MS assay that is appropriate for use in patient management - in every scenario.
Conclusions & Discussion
You will take home a number of key developmental tools and practical solutions to get the most out of your Internal Standards and know when and hopefully how to correct implicit errors in their use to provide high quality actionable results using LC-MS/MS.
Translating from Troubleshooting to Quality Improvement
William Clarke, PhD, MBA, DABCC
Johns Hopkins University School of Medicine
Dr. Clarke received his Ph.D. in Analytical Chemistry from the University of Nebraska in Lincoln in 2000, followed by a post-doctoral fellowship in Clinical Chemistry at the Johns Hopkins School of Medicine, ending in 2002. In addition, he received an MBA focused on medical services management from the Carey School of Business at Johns Hopkins in 2007. Following his post-doctoral fellowship, he remained at Johns Hopkins, where he is a Professor in the Department of Pathology, as well as the director of Point-of-Care Testing, Reference Toxicology, and Phlebotomy for the hospital. He also serves as the Vice-Chair for Quality and Regulatory Affairs in the Department of Pathology. His research interests include clinical mass spectrometry, method development and evaluation for therapeutic drug monitoring, clinical toxicology, point-of-care testing, and development/validation of biomarkers for use in drug management. Dr. Clarke has published as author or co-author over 170 peer-reviewed manuscripts or book chapters, and is the Co-Editor of the textbook Contemporary Practice in Clinical Chemistry.
Cases are reviewed that range from simple human error during routine production, to evolution of method protocols to add robustness, to process improvements implemented to cope with too many specimens from a large clinical trial. The perspective of troubleshooting as a filter that can uncover issues to then address with quality improvement processes is highlighted.
1. list basic approaches to LC-MS/MS trouble shooting
2. discuss common causes for LC-MS/MS assay problems
3. formulate strategies for LC-MS/MS troubleshooting, and converting them to QA processes.
Alan Rockwood, PhD, DABCC is Professor (Clinical) Emeritus of Pathology at the University of Utah School of Medicine in Salt Lake City, Utah, USA. Originally trained in Physical Chemistry, he performed research on the fundamentals of mass spectrometry and instrumentation development before focusing his career on Clinical Chemistry. He became certified by the American Board of Clinical Chemistry and has held a Certificate of Qualification in Clinical Chemistry from the New York State Board of Health. Currently, his primary area of research is the development of mass spectrometry-based quantitative assays for targeted analytes of clinical interest, including small molecules and more recently proteins and peptides. Additionally, he maintains a smaller research effort on fundamentals of mass spectrometry, particularly novel approaches for isotopic profile calculations. He has published >150 papers in peer reviewed journals.
Learn from the experiences gained at a large reference laboratory that was an early adopter of LC-MSMS and successfully executed high test volumes and sophisticated methods. Follow the painstaking inquiries necessary to solve devious and difficult cases that occurred with LC-MSMS testing for endocrine and other analytes. Quality measures that can detect or prevent subtle variance from normal method performance are reviewed.
1. outline an overall strategy for troubleshooting problems in a clinical mass spectrometry lab,
2. explain the relationship between record keeping and troubleshooting in a clinical mass spectrometry lab
The Basics of LC-MSMS Troubleshooting: Tools, Strategy, Cases
Judy Stone, MT (ASCP), PhD, DABCC
Clinical Chemist (retired)
Judy Stone, MT (ASCP), PhD, DABCC has worked with LC-MS in diagnostic laboratories since 1999. Her clinical practice involved small molecule method development, instrument to instrument and instrument to LIS interfacing, LC-MS automation, monitoring quality of LC-MS methods in production and staff training for clinical LC-MSMS. She served as faculty chair for the 2009 AACC online certificate program “Using Mass Spectrometry in the Clinical Laboratory”, as a scientific committee member for the MSACL Practical Training track, and was editor-in-chief for the AACC Clinical Laboratory News quarterly feature series on Clinical LC-MS. She enjoys documenting and presenting esoteric as well as absurdly common LC-MS problems in creative ways in order to help trainees learn troubleshooting (and avoid repeating her mistakes).
Learn the tools and strategies of LC-MSMS troubleshooting and work through cases found all too often during routine operation. Selected best practices for robust instrument operation, preventative maintenance and basic repairs are presented.
1. list 3 troubleshooting tools for LC-MSMS,
2.create a calendar for LC-MSMS preventative maintenance,
3.describe checks to distinguish an LC problem from a Sample Preparation mistake from an MSMS loss of sensitivity.