Translating Pre-Clinical Research to Clinical Patient Care™

Educational Grantee Partners:

Distinguished Contribution Award Lecture

On the Award

Tue April 04 @ 17:40 (05:40 PM) in Steinbeck
Lecture Title Pending
Jennifer Van Eyk
Cedars-Sinai Heart Institute

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


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

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

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

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.