Lecture Title Pending Jennifer Van Eyk 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.
Plenary Lectures
Tue April 04 @ 16:50 (04:50
PM) in Steinbeck
Translating Multiplexed Proteomic Assays to the Clinic and Beyond: Lessons from a Road Less Traveled Timothy Collier 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)–associated proteins. The validated clinical assay provides insight into a patient’s cholesterol efflux capacity (the ability of HDL cholesterol to transport cholesterol away from the artery wall). The assay helps assess the patient’s risk for developing coronary artery disease and, ultimately, cardiovascular death. The assay is also a component in several clinical studies to further assess its utility. Furthermore, the research framework upon which this assay was designed continues to yield new insights into other pathologies, including non-alcoholic fatty liver disease (NAFLD), metabolic syndrome, and diabetes. In this presentation I will summarize our efforts, our successes, and lessons learned on the road from basic research to clinical deployment.
Wed April 05 @ 08:30 (08:30
AM) in Steinbeck
Molecular Phenomics in Systems, Synthetic, and Chemical Biology John McLean Department of Chemistry, Vanderbilt University
John A. McLean is Stevenson Professor of Chemistry, Chair of the Department of Chemistry, Associate Provost for Graduate Education, and Director of the Center for Innovative Technologies at Vanderbilt University. He is an elected Fellow of the National Academy of Inventors and the American Association for the Advancement of Science. He earned his PhD at George Washington University in 2001 and subsequently performed postdoctoral research at Forschungszentrum Jülich in Germany and then at Texas A&M University before beginning at Vanderbilt University in 2006. McLean and colleagues have focused on the conceptualization, design, and construction of ion mobility-mass spectrometers and structural mass spectrometers, specifically targeting complex samples in systems, synthetic, and chemical biology. His group applies these strategies to forefront translational research areas in drug discovery, personalized medicine, and ‘human-on-chip’ synthetic biology platforms. McLean has received a number of awards, including his laboratory serving as an Agilent Thought Leader Laboratory, a Waters Center of Innovation, the Chancellor’s Award for Research, the Thomas Jefferson Award, Excellence in Teaching Award from the student members of the American Chemical Society, a Defense Threat Reduction Agency Research Award, an American Society for Mass Spectrometry Research Award, and the Bunsen–Kirchhoff Prize from the GDCh (German Chemical Society), among others. He has served in many service roles to the profession including serving terms on the boards of professional societies, scientific companies, and major journals. He has published over 200 manuscripts and received over 30 patents in these and allied areas.
The human genome project is recognized as being one of the most successful big science projects in modern history. One of the primary motivational underpinnings to undertake the HGP was to better understand what made us human and healthy - and how to use this code to improve the human condition by better understanding disease and potential treatment. While the frontiers of our knowledge expanded dramatically, we also uncovered profound biological complexity that we could not understand. This led to the current frontier in the measurement science of molecular phenomics, to catalog the broad-scale changes in the molecular inventory in cells, tissues, and biological fluids at a specific biological state, or in response to exposures and lifestyle choices. In phenomics, we seek to characterize the comprehensive molecular basis of biology (including DNA, RNA, proteins, lipids, carbohydrates, metabolites, and all of their nuances), in both space (e.g. at a cell, tissue, and organismal level) and time (e.g. healthy versus disease state). This places enormous demands on measurement technologies (including minimal sample preparation, fast measurements, high concentration dynamic range, low limits of detection, and high selectivity) and computational approaches to organize the millions of potential species present in vanishingly small spatial coordinates. The interplay between phenomic datasets and bioinformatics forms the nexus of translating phenomics data into actionable information and understanding.
Advances in computational biology rely heavily on the experimental capacity to make omics measurements, i.e. integrated proteomics, metabolomics, lipidomics, glycomics, among many others. Ion mobility-mass spectrometry (IM-MS) provides rapid (ms) gas-phase electrophoretic separations on the basis of molecular structure and is well suited for integration with rapid (us) mass spectrometry detection techniques. This report will describe the fundamental strategies for IM separations and recent advances in IM-MS integrated omics measurement strategies in the analyses of complex biological samples of interest in systems, synthetic, and chemical biology. New advances in artificial intelligence and machine learning based on developments in internet commerce and astronomy will also be described to approach biological queries from an unbiased and untargeted perspective and to quickly mine these massive datasets. These techniques will be highlighted through selected examples ranging from clinical applications of targeted panels, to the creation of microfluidic human-organs-on-chip to replace animal testing in drug development workflows, to probing the outcomes of fast genetic editing experiments (using CRISPR) in the optimization of synthetic biology for fine and commodity chemical production to potential advances in clinical measurements. While enormous challenges remain, the promise is immense – comprehensive diagnostics and predictive capabilities for health and medicine of importance to society and beyond.
Keynote Lectures
Differential Ion Mobility Spectrometry: Understanding the Chemistry in the Mass Spectrometer and How That Affects What Is Detected Gary Glish University of North Carolina
Professor Gary L. Glish earned his Ph.D. from Purdue University under the guidance of Graham Cooks. He spent 12 years as a staff scientist and group leader at Oak Ridge National Laboratory during which time he designed and built the first QTOF instrument and his group was the first to interface ESI to a quadrupole ion trap mass spectrometer. He left Oak Ridge to take his current position as a faculty member in the Department of Chemistry at the University of North Carolina. His group there focused a lot on the fundamentals and development of applications for quadrupole ion traps. More recently the lab has been involved in the development of differential ion mobility spectrometry and development of ionization techniques for real-time analysis of aerosols. He was an associate editor for the Journal of the American Society for Mass Spectrometry for 17 years and has served as VP for Arrangements, VP for Programs, and President of the American Society for Mass Spectrometry.
Differential Ion Mobility Spectrometry (DIMS) is a powerful tool that can help improve targeted detection of analytes using mass spectrometry (MS). DIMS has a number of advantages over more conventional drift type ion mobility techniques, but currently lacks the ability to determine collisional cross-sections. Some of the advantages of DIMS are: it is readily compatible with any type of mass analyzer; it is more orthogonal to MS because the separation is not based just on cross-section; and gas phase chemistry can be used to dramatically affect separation of analytes that are isomeric/isobaric and even have the same cross-section. A very under-appreciated aspect of DIMS is its ability to provide insight into the ionization chemistry and how that chemistry can significantly distort the resulting mass spectrum. This presentation will provide an overview of DIMS, examples of improvement of targeted analysis using DIMS with and without gas phase chemistry, and examples of how DIMS can provide understanding of chemistry occurring in the mass spectrometry experiment that can lead to inaccurate conclusions.
Advancing Neuroscience Research via Novel Application of Ion Mobility Mass Spectrometry (IM-MS) Lingjun Li 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.
Naturally occurring D-amino acid substitution, also known as amino acid D-isomerization, has been observed in many disease-associated peptides and proteins, including amyloid beta (Aβ), one of the putative biomarkers and drug targets for Alzheimer’s disease. Aβ is of significant interest due to the prevalence of post-translational D-isomerization in AD brain samples. While many prior reports have described technical advancements associated with the chiral discrimination and separation of D-amino acid containing peptides, there remains a dearth of tools capable of targeting Aβ42 stereochemistry. Ion mobility-mass spectrometry (IM-MS) has increasingly become an important alternative for the chiral separation of Aβ stereoisomers. IM-MS offers high analytical speed, low sample consumption and the ability to resolve small structural differences in peptide analytes, driven by recent technological advancements in IM-MS. In this talk, I will present a multi-dimensional IM-MS-based structural analysis strategy to facilitate the study of the chiral effects on monomer structure, oligomeric propensity, and receptor binding for Aβ peptides. Furthermore, analytical strategies to enhance peptide epimer differentiation and for site-specific localization of D-amino acid containing peptides will be presented. Finally, I will discuss our recent efforts in developing a high-resolution ion mobility-enabled sn-position resolved lipidomics strategy for probing phospholipid dysregulation in the brain of a mouse model for Alzheimer’s disease.
