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.
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.
Objective
To provide an interactive forum in which attendees will be introduced to critical aspects of clinical protein measurements.
Summary
The motivation for using mass spectrometry to quantify proteins in clinical research and in clinical care will be discussed as part of this interactive workshop. Technical topics uniquely affecting quantitative protein and peptides measurements by mass spectrometry will be a point of emphasis. Case studies from assay inception through validation will be presented and participants will work interactively to critique various aspects of clinical proteomic measurements.
Syllabus
- Protein vs Peptide Measurands
- Workflows
- Sample Preparation (Digestion & Enrichment)
- Internal standards
- Calibration
- Validation
- Quality control
800
1200
Workshop: Why We Fail at Biomarkers
Location: De Anza 3
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).
Objective
This workshop is designed to teach attendees reasons why most biomarkers do not translate to clinical diagnostics as a way to improve the process for future research
Summary
Biomarker discovery is one of the major areas of clinical research especially in metabolomics yet less than 1% of published biomarkers translate to clinical diagnostics. Biomarker discovery generally starts in phase 1 with a few samples to identify a biomolecule that differentiates the disease or disorder under investigation from control samples. Once a biomolecule is selected a targeted quantitative method would be developed in phase 2 to use on a larger number of samples to validate the results from phase 1. There are several common reasons for biomarker failure such as using samples that are not representative of the clinical population, not including diversity in the initial discovery phase, improper use of statistical approaches, not having a sufficient number of samples and improper quality control for analysis. With the growth of metabolomic methods recently, a discussion on approaches to help improve phase 1 of biomarker discovery is important to have confidence that the selected markers are indeed unique.
Syllabus
- Metabolomics in clinical research
- Quality control for better method assessment
- Experimental design
- Statistical analyses with validation
- Real-world samples
800
1200
Short Course: Data Science 101 : Breaking up with Excel: An Introduction to the R Statistical Programming Language
Location: Bonsai
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.
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.
** Part In-Person (optional, also available pre-recorded) and Part Online **
This is the first segment (4 hr) of a three segment (16hr total), part in-person (optional) and part online, short course.
Segment 1 will be available both IN-PERSON on April 5 at the MSACL 2022 conference in Monterey, CA and ONLINE (pre-recorded) if you can't make it in person. Registration for Segment 1 is free (although to attend on-site you must be registered for MSACL 2022).
Segments 2 and 3 will take place ONLINE on April 29-30, 2022.
While the first SEGMENT is FREE, SEGEMENTS 2 and 3 that occur only ONLINE are fee-based. You can REGISTER HERE.
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Does Excel lag on you when you open a file bigger than 1000 rows? Has it ever changed your data to a date against your will? Are you ready to jump right past Tableau and into the world of Data Science using a real programming language?
Well, your wait is over because at MSACL we again will be offering a course for complete programming newbies that will help you get going analyzing real data related to LC-MS/MS assay development, validation, implementation and publication.
The only background expected is the ability to use a spreadsheet program. The skills that you will acquire will allow you to take advantage of the many tools already available in the R language and thereafter, when you see that your spreadsheet program does not have the capabilities to do what you need, you will no longer have to burst into tears.
The course will be run over three days (one in person to start and two online later) and time will be evenly split between didactic sessions and hands on problem solving with real data sets. Drs Holmes and Bunch will adopt a “no student left behind policy”. Students will be given ample time to solve mini problems taken from real life laboratory work and focused on common laboratory tasks. All attendees will need to bring a laptop with the R language installed R Studio interface installed. Students may use Windows, Mac OSX or Linux environments. Both R and R studio are free and open-source. No cash required.
Students should be prepared for learning what computer programming is really like. This may involve some personal frustration but it will be worth it.
Obtaining the Software
!!! DOWNLOAD PROGRAM PACKAGES PRIOR TO ARRIVAL ONSITE !!! THERE WILL NOT BE OPEN INTERNET WIFI IN THE CONFERENCE CENTER.
!!! POWER : Make sure your computer is charged to hold power for 4 hrs, as power outlets may not be available.
The major types of R variables: vectors (numerical, character, logical), matrices, data frames and lists.
The important classes: numeric, character, list and changing between them
Importing data from Excel
Dealing with non-numeric instrument data
Manipulating and cleansing your data
Exporting data to Excel-like format.
Basics of tidyverse: dplyr, filter, mutate, join
Regressions: ordinary least squares,Passing Bablok, Deming, weighted regressions.
Non-linear regressions
Looping: Doing things repeatedly
group_by and summarize
Writing your own functions
Making highly customized figures with base plot or ggplot
Putting it all together projects:
Preparing method comparison regression and Bland Altman plots
Preparing mass spectrometry data for upload to LIS.
800
950
Short Course: LC-MSMS 101 : Hands-On Training Session (GROUP 1)
Location: Colton
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).
Jacqueline Hubbard, PhD, DABCC
Hubbard Lab Consulting
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. In 2022, she became the Laboratory Director at Three Rivers Diagnostics, a reference laboratory in Pittsburgh, PA. Her research focus still includes mass spectrometry method development and toxicology test interpretation.
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.
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.
900
1200
Workshop : How to Convince Admin THEY Want to Buy You a Mass Spectrometer
Location: De Anza 2
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.
Juan David Garcia, MBA MT
University Of Texas Medical Branch
JUAN D. GARCIA, MBA MLS
Mr. Garcia has more than 20 years of extensive experience in healthcare and medical laboratory industry having worked and managed a wide range of settings including large medical centers with multiple in-house laboratories, multi-hospital systems, academic healthcare institutions, and hospital-based outreach facilities. He specializes in business and strategic planning, operations management, operations analysis & improvement, quality assessment and improvement, lean/six sigma process improvement, information system/LIS integration, system evaluation, selection and implementation, vendor consulting and subrogation, outreach development as well as team building and employee engagement.
Mr. Garcia holds a strong technical knowledge in multiple lab disciplines through the earlier years of working in the laboratory field. The combination of superior technical and business qualifications allowed him to understand healthcare and laboratory business from multiple perspectives and have the ability to analyze an organization’s critical business requirements, identify deficiencies and opportunities and provide innovative and cost-effective solutions for enhancing operations with financial success.
Mr. Garcia currently works as the Administrative Director for the Laboratory Services at University of Texas Medical Branch in Galveston, TX. Prior to this, he directed the Central Laboratory Services at New York Presbyterian Hospital Weill Cornell Medical Center in New York and managed the Laboratory Services at the University of Miami in Miami Fl. He also is the founder and former Director of HCLA (HealthCare & Laboratory Advisors) consulting firm.
Mr. Garcia received his MBA in Management and HealthCare Management from the Business School at University of Miami and a Bachelor of Science in Medical Laboratory Science from University of Valle in Cali Colombia. He is also Lean/Six Sig Sigma Green Belt certified and an active member of several management and professional organizations.
Objectives
The objective of this workshop is to give attendees the knowledge necessary to put together a convincing business case for purchasing a mass spectrometer. This knowledge will be imparted by presenting and discussing successful and unsuccessful examples of such business cases. Throughout the course, essential business terminology will be presented and explained.
Summary
Many laboratorians can discuss the benefits of implementing mass spectrometry into the clinical laboratory. From improved confidence in results to minimization of interferences, there are substantial and well-discussed benefits to mass spectrometry. Unfortunately, mass spectrometers cost money and the individuals empowered to write checks rarely relate to such technical justifications. This workshop is designed to help clinical laboratorians understand what factors matter to financial decision makers. The presenters include a clinical laboratorian with experience successfully acquiring mass spectrometers and an experienced administrator with significant laboratory and financial expertise. The presenters will walk attendees through the process of preparing a business case. Attendees will be presented with numerous examples of business cases that need improved and the attendees will be given the chance to discuss what is wrong and what needs to be done to fix them. Attendees will also be given a chance to submit their own personal business cases ahead of time if desired. These can be discussed in private after the workshop or (with attendee permission) can be discussed in part as part of the workshop. The goal is to prepare attendees to put together and present a business case that supports the acquisition of a mass spectrometer in terms that matter to financial decision makers.
Syllabus/Topics
How to assemble the worst business case ever (and guarantee failure)
Attendees will begin the session with an introduction to the worst possible business case one can present. The numerous flaws will be pointed out and addressed in an effort to highlight the many ways business cases can go wrong.
From LCMS and qTOF to ROI and DEPR (speaking the language of finance)
After attendees have a chance to see what not to do, it will be time to discuss what administrators/finance officers are looking for in a business plan. The goal is that attendees walk away with an understanding of the important terms and metrics their business cases will be evaluated by. In addition, an overview of hospital accounting and do's and don't's of capital equipment purchasing will be given.
Estimating costs
The cost of a mass spectrometer is far more than the instrument itself. This section will help attendees begin to consider everything they need to account for when proposing how much mass spectrometry will cost- labor, supplies, service contract, etc.
Estimating reimbursement
This section will cover how to estimate revenue- whether it is insourcing from a reference lab or setting up a new service line. The importance of payer mix and inpatient vs outpatient will be addressed
What's wrong with my business case?
Ending where the course started, the final section will cover examples of business cases. These cases will be used to illustrate cases that are very strong and those with weaknesses that can be improved. If submitted by attendees ahead of time, these example cases will be anonymized versions of those submissions.
1000
1150
Short Course: LC-MSMS 101: Hands-On Training Session (GROUP 2)
Location: Colton
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).
Jacqueline Hubbard, PhD, DABCC
Hubbard Lab Consulting
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. In 2022, she became the Laboratory Director at Three Rivers Diagnostics, a reference laboratory in Pittsburgh, PA. Her research focus still includes mass spectrometry method development and toxicology test interpretation.
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.
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.
** Supplemental Hands-On Segment In-Person : Main Course is Online **
This is the supplemental bonus segment (2 hr) of a 16 hour online short course taking place on March 11-14, 2022. Attendance at this in-person segment is free, but REQUIRES pre-registration (separate from conference registration, coming soon) with priority given to online course registrants. There will be two instances of this segment (Group 1 and Group 2, both the same), with each to be capped at 20 participants.
This two hour workshop is a supplement to the MSACL Online Short Course – “Getting Started with Quantitative LC-MS/MS in the Diagnostic Laboratory (LC-MS 101)”. The short course will be offered online, March 11-14, 2022 (register here). The hands-on workshop content is designed for attendees from the online short course, but the short course is not a prerequisite. Anyone starting out with quantitative LC-MS troubleshooting may find it useful.
Format and Content
The first 50 min session will include brief instructor demonstrations and then ample hands-on time for attendees to practice troubleshooting tasks, such as
- cutting (and recutting) PEEK tubing correctly
- connecting (and reconnecting) PEEK fittings to LC columns, other components
- changing LC pump check valves
- changing LC injection valve rotor seals
- reviewing chromatography problems caused by leaks, tubing/fitting mistakes and damage, excess LC dead volume, and aged LC components
The second 50 min session is a discussion of real world instrument troubleshooting cases from the instructors’ laboratories. Aside from the examples presented, the goal is to develop a standardized approach to troubleshooting complex LC-MS systems, including
- Know your LC flow path and LC components, how to avoid damaging the MS/MS
- How to look for leaks and sources of overpressure
- Using chromatogram overlays, pressure traces, maintenance chart review, system suitability testing and MS/MS infusion to locate the problem within the instrument
1000
1145
Workshop: Design of Experiments for Development and Optimization of LC-MS Clinical Diagnostic Assay
Location: Steinbeck 1
Margret Thorsteinsdottir, PhD
University of Iceland
Professor in Pharmaceutical Analytical Chemistry at the Faculty of Pharmaceutical Sciences, University of Iceland and R&D Director of ArcticMass LTd, Reykjavik, Iceland. Dr. Thorsteinsdóttir received her PhD from Uppsala University, Sweden in 1998. From 2000 to 2009 she was the managing director of Bioanalytical Laboratories at deCODE Genetics, Reykjavik, Iceland. She has extensive experience in development of analytical methods for metabolite profiling and quantification of clinical biomarkers in various biofluids utilizing chemometrics with the goal of improved clinical management of patients towards personalized patient care.
Her current research interest includes studies of lipid metabolism in cancer cells and profiling plasma derived biomarkers for early detection of BRCA-related breast cancer. She is responsible for implementation of clinical mass spectrometry for support of diagnostics and therapeutic drug monitoring in collaboration with ArcticMass and the Landspitali University Hospital, Reykjavik, Iceland with major focus on quantitative targeted proteomics for clinical diagnosis. She is a principal investigator of the Icelandic Research Rannis projects, profiling metabolites for breast cancer diagnosis and search for novel biomarkers for early breast cancer diagnosis by metabolomics. Dr. Thorsteinsdóttir is a principal investigator for the Marine Biotechnology ERA-net project CYNOBESITY and the Horizon 2020 project MossTech, with the main task to isolate, identify and structurally characterize bioactive compounds from cyanobacteria, Icelandic mosses and liverworts. She is one of the founders of Females in Mass Spectrometry (FeMS), she is a vice-leader of the working group clinical significance and applications of (epi)lipidomics in the pan-European network, EpiLipidNET and vice-chair of the Nordic Metabolomics Society.
Finnur Eiriksson, PhD
ArticMass
Objectives
The objective of the workshop is to provide an introduction into design of experiments (DoE) for clinical application with special focus on optimization of MS-based bioanalytical assays. The workshop is focused on practical implementation of DoE and will demonstrate how method development of UPLC-MS/MS clinical diagnostic methods can become much more efficient by utilizing DoE.
Summary
The chemometric approach, design of experiments (DoE) is an efficient tool for development and optimization of UPLC-MS/MS for quantification of biomarkers in complex biological matrices. The UPLC-MS/MS platform is composed of several processes which involves many experimental factors that need to be simultaneously optimized to obtain maximum sensitivity with adequate resolution at minimum retention time. DoE offers a practical approach for performing experiments in accordance to predefined plan, modelling by empirical functions, and graphical visualization. Basic concept of DoE will be presented with emphasis on practical implementation of DoE which include the three main stages, screening, optimization, and robustness testing. Example from optimization of a UPLC-MS/MS method for clinical diagnostic purposes and therapeutic drug monitoring will be used to show the cost-effective benefit of DoE, where it allows the effect of variables to be assessed with only a fraction of the experiments that would be required by changing one-separate-factor-at-time (COST) approach. A fractional factorial design was used for experimental screening to reveal the most influential experimental factors. When multi-levels qualitative factors were included in the screening experiments D-optimal design was applied. Significant factors were studied via central composite design and related to sensitivity, resolution and retention time utilizing partial least square (PLS)-regression. A specific and reliable UPLC-MS/MS assay for simultaneous quantification of urinary 2,8-dihydroxyadenine (DHA) and adenine was optimized efficiently with DoE. The assay has been implemented for clinical diagnosis and therapeutic drug monitoring of patients with adenine phosphoribosyltransferase (APRT) deficiency, which is an inborn error of purine metabolism.
Syllabus
-- Design of Experiments (DoE) - Get it right from the beginning
-- Basic concept and assessment of DoE
-- Optimization of LC-MS based clinical assay by DoE
1200
1400
Short Course & Workshop Lunch Mixer
Location: Steinbeck Foyer
1215
1345
Workshop: Ion Mobility in the Clinical Lab?
Location: Steinbeck 1
Christopher Chouinard, PhD
Clemson University
I received my PhD from University of Florida in 2016, where I developed ion mobility-mass spectrometry (IM-MS) methods for steroids and vitamin D metabolites. I then worked as a post-doctoral research at Pacific Northwest National Laboratory, building Structures for Loss Ion Manipulations (SLIM) ion mobility instrumentation for application in metabolomics and proteomics. In 2018, I began my independent career as an Assistant Professor at Florida Institute of Technology. I have since moved to Clemson University in August 2022. Work in my research group focuses on ion mobility-mass spectrometry (IM-MS)-based methods and technology, including structurally selective reactions for improved characterization of steroids and other controlled substances.
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.
Objective
Workshop attendees will learn about the basic operating principles of various ion mobility techniques, the potential benefits and challenges to its routine implementation in the clinical lab, and several potential applications.
Summary
Ion mobility-mass spectrometry (IM-MS) has become a cornerstone of biomedical analysis, with applications ranging from isomeric small molecule differentiation to the study of protein structure and folding dynamics. Despite its many advantages, IM-MS has yet to see routine implementation in the clinical lab due to challenges in quantitation, limited universal standards, data processing software, and reproducibility across different IMS techniques/vendor platforms. This workshop will introduce the common IMS techniques (e.g., drift tube, traveling wave, FAIMS/DMS, etc.) and their operating principles, expanding upon the benefits of incorporating IMS into conventional LC-MS/MS workflows and discussing the challenges that have limited such incorporation. Finally, an overview of current applications (including metabolomics, lipidomics, and proteomics examples) will be provided.
Objective 1: Understand the basic operating principles of IMS and the differences between the different techniques (e.g., drift tube, traveling wave, FAIMS/DMS, etc.)
Objective 2: Recognize the benefits and limitations to incorporating IMS into conventional LC-MS/MS workflows in the clinic
Objective 3: Become familiar with current (and potentially future) applications of IMS to the clinical lab
Syllabus
1. Basic Operating Conditions of IMS: Electric field application, experimental conditions (temperature, pressure, gas composition)
2. Different IMS techniques: Drift tube/traveling wave, field asymmetric/differential mobility, emerging techniques (i.e., TIMS, SLIM, cIMS, etc.)
3. Applications: Current examples from metabolomics, lipidomics, and proteomics
1400
1425
Welcome Orientation
Location: De Anza
Chris Herold, PhD, MBA
MSACL
Chris Herold is a scientifically-trained entrepreneur. He received his BS in Chemical Engineering from the University of Virginia, after which he left the US to spend nine months in Lausanne, Switzerland at Scitec SA working on a Perkin Elmer Q-Mass quadrupole to analyze soil and water samples for toxic components. He returned to the US and completed his PhD in Molecular Pathology at the University of California, San Diego (UCSD) and then joined the start-up, Prediction Sciences (PS). While at PS he wrote and directed SBIR grants from the NIH and NSF as Principal Investigator with the goal of identifying correlations between SNP profiles and drug response (pharmacogenomics).
He left PS to pursue an MBA from Cornell University and then joined the start-up Arrayomics, which focused on the development of liquid microarray technology. He is a founding board member of MSACL and, as President & COO, has been responsible for its operational logistics since the organization's inception. He is the managing editor of the Journal of Mass Spectrometry & Advances in the Clinical Lab (JMSACL), which is owned by MSACL and published by Elsevier.
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.
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).
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.
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 is 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.
Cory Bystrom, PhD
Ultragenyx
Opening Orientation with (1) a brief welcome from Chris Herold, (2) a brief presentation from Stephen Master (President of AACC), (2) an introduction to our new JMSACL co-Editors-in-Chief, Kara Lynch and Tim Garrett (and acknowledgement of founding co-Editors-in-Chief, Alan Rockwood and Michael Vogeser, who brought the journal to this point), and (3) an official welcome from the Chair of the MSACL 2022 Steering Committee, Cory Bystrom.
1425
1445
State of the Science
Location: De Anza
Cory Bystrom, PhD
Ultragenyx
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.
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.
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.
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Location: De Anza Foyer
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Beyond the Human Genome: A Million Person Precision Population Health Project
Location: De Anza
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.
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Location: De Anza Foyer
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The Clinical Laboratory Perspective on Wellness Testing: Let’s Take a Look Under the Hood
Location: De Anza
Geoff Baird, MD, PhD
University of Washington
Geoffrey Baird, M.D., Ph.D., is a board certified pathologist at UW Medicine, and professor and acting chair of Laboratory Medicine and Pathology. He directs the Clinical Chemistry Laboratory at Harborview Medical Center.
Dr. Baird’s goal is to provide the highest quality lab services to patients in the UW community and Pacific Northwest region.
Dr. Baird earned his M.D. and Ph.D. from UC San Diego. He is board-certified in Anatomic Pathology, Clinical Pathology and Clinical Chemistry. His clinical and research interests include lab test utilization management, proteomics, tissue analysis, general laboratory medicine, pathology and pathophysiology of organ systems and anatomic pathology.
As medical science continues to make gains in the elucidation of disease pathophysiology and the discovery of cures , some have questioned the value of dedicating dwindling financial resources to maintaining wellness rather than to fighting disease per se. While both approaches are meritorious and complementary, neither approach is alone sufficient to ensure the health of a population. One major problem with the focus on wellness is the Bayesian dilemma that the positive predictive value of clinical laboratory testing in apparently healthy people is often low, as the specificities of few clinical tests are high enough to ensure that most positive results are true. The impact of this dilemma on laboratory-based wellness approaches will be discussed.
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Location: De Anza Foyer
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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
Location: De Anza
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.
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’t sound appealing, you would be in the majority! While the analytical advantages of mass spectrometry resulted in it decisively displacing ligand binding methods as the gold standard approach for protein quantitation, making progress on the routine testing front has taken additional effort. Here we look at how re-evaluating the status quo in clinical proteomics has helped us take leaps forward and implement protein mass spectrometry to improve patient care.
About the Award
