7:30 AM - 7:00 PM - Registration
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Registration and Information Desk
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8:00 AM - 9:00 AM - Plenary Session
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Robert J. Cotter New Investigator Award Plenary Session
The Endurance of Proteins in Context
The “endurance” of a protein lies in its activity and lifetime. The dynamic decoration by post-translational modifications (PTMs) during the protein lifespan, normally in an amino acid site-specific manner, can induce protein activity alteration. On the other hand, coordinated protein synthesis, turnover, and degradation can determine a protein’s lifetime in cells. Both protein PTM and turnover can now be well measured in a large scale by current mass spectrometry (MS) techniques, such as data-independent acquisition (DIA)-MS. In this presentation, we will discuss how we develop and apply MS methods to quantify and understand protein PTM dynamics (mainly phosphorylation) and turnover behaviors in different biological contexts, such as cancer aneuploidy, cell starvation, and cell fate decision. In particular, we will discuss an example of a lung cancer model of isogenic immortalized cells discordant for chromosome 3 aneuploidy, in which we demonstrated that protein turnover control is not universal in all “gain-type” and “loss-type” aneuploidies. We will also cohesively discuss other relevant ongoing projects in the Liu Lab. In addition, I look forward to sharing personal career experience with young proteomic scientists and early investigators.
Presented By:
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Yansheng Liu, Assistant Professor, Department of Pharmacology, Yale University School of Medicine, New Haven, CT, United States
(Bio)
Yansheng Liu is an Assistant Professor in the Department of Pharmacology at Yale University School of Medicine. He is also a group leader in quantitative proteomics at the Yale Cancer Biology Institute and Yale Cancer Center. Dr. Liu received his Ph.D. in Biomedical Sciences from the Chinese Academy of Sciences in 2011. He then carried out his post-doctoral training at ETH Zurich, Switzerland, under the mentorship of Ruedi Aebersold. In December 2017, Yansheng joined the faculty at Yale and began his independent career. His research program is focused on analyzing protein turnover and post-translational modifications for understanding cancer aneuploidy, cellular signaling transduction, and biodiversity. The Liu Lab also aims to contribute to the development of multiplexed data-independent acquisition mass spectrometry (DIA-MS) approaches. To date, Dr. Liu has co-authored 65 research and review articles. He has received the 2019 ASMS Emerging Investigator, the 2021 ASMS Research Award, the 2021 HUPO ECR Award (winner), and the 2023 US HUPO Robert J. Cotter New Investigator Award. He serves as an editorial board member of Proteomics and Proteomics-Clinical Applications, a scientific advisory board member for Review Commons, and a member of the HUPO Awards Committee and HUPO ETC Committee.
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9:00 AM - 10:00 AM - Lightning Session
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Lightning Talks - Round 02
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10:00 AM - 11:30 AM - Poster Session
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Poster Session 02 and Exhibitor Viewing
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11:30 AM - 12:50 PM - Parallel Sessions
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Parallel Session 07: Protein Dynamics and Turnover
This parallel session will feature two invited presentations, followed by two selected oral abstract presentations.
Optimizing dynamic SILAC based protein turnover measurements in vivo
The last years have shown how precise measurements of protein turnover – the interplay between protein production and loss - yield important insight about gene expression regulation. Moreover, several different approaches have been introduced to provide precise turnover measurements for thousands of proteins. These include dynamic SILAC measurements which were either followed by deep fractionation and data dependent acquisition (DDA) proteomics measurements, also sometimes combined with TMT labeling, or by data independent acquisition (DIA) measurements of unfractionated samples. We are systematically testing these different approaches in two mammalian in vivo model systems. First, we are determining protein turnover changes in mouse organoids derived from pancreatic tumor and metastases. Second, we are measuring protein turnover in brain tissue from wildtype mice and mice where an important regulator of protein homeostasis is knocked out. In my talk I will share insight about our ongoing work to optimize the yield of reliable protein turnover measurements in both these systems and the advantages and challenges associated with all the tested approaches to measure protein turnover.
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Marko Jovanovic, Assistant Professor, Columbia University, New York, NY, United States
(Bio)
Marko Jovanovic did his PhD in the lab of Michael Hengartner at the University of Zurich, Switzerland. In close collaboration with the Ruedi Aebersold lab at the ETH Zurich, they developed novel large-scale approaches to identify microRNA targets genes in C. elegans. After his PhD, he joined the group of Aviv Regev at the Broad Institute of MIT and Harvard in Cambridge, USA. In collaboration with the Steven Carr lab at the Broad Institute, they developed new methods to integrate transcriptomics and proteomics data in order to gain new insight about how protein level changes are regulated during the immune response of dendritic cells. Marko started his own research group at Columbia University in 2017. The overarching research goal of his lab is to understand the principles and mechanisms by which translational regulation controls the dynamics of gene expression and therefore affects processes like differentiation, stress response and pathogenesis.
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Novel Gene-Specific Translational Mechanism in Human Diseases
By largely unknown mechanisms, COVID-19 patients with pre-existing chronic inflammatory diseases are vulnerable to severe symptoms. Excessive serum cytokines and abnormally activated macrophages are found in the bronchoalveolar lavage fluid of these severe COVID-19 patients. Thus, effective therapies to minimize mortality depends on a mechanistic understanding of SARS-CoV-2-induced pathogenesis. We report a novel gene-specific translation mechanism that suppresses synthesis of proteins associated with SARS-CoV-2 transmission, impaired T cell function, blood clotting, and the host hyperinflammatory response. First, we employed our chromatin-activity based chemoproteomics (ChaC) approach to dissect the interactome/pathways associated with G9a, a histone methyltransferase whose mRNA was upregulated with virus load in COVID-19 patient peripheral mononuclear cells. This ChaC analysis revealed that constitutively (enzymatically) active G9a interacted with multiple regulators of translation and ribosome biogenesis. This finding implicated a noncanonical function of G9a in the translational regulation of COVID-19 immunopathogenesis. Accordingly, using our translatome proteomics approach, we identified and profiled proteins whose translation depended on G9a activity, that is, G9a upregulated the widespread translation of a battery of COVID-19 pathogenesis-related genes. Mechanistically, based on ChaC identification of G9a interaction with METTL3, an N6-methyladenosine (m6A) RNA methyltransferase, we found that G9a methylates the nonhistone protein METTL3 to co-upregulate m6A-mediated translation (synthesis) of specific proteins functionally associated with immune checkpoint and hyperinflammation. Therefore, we conducted a correlated multiomics study on the m6A/METTL3 transcriptome, proteome, and phosphoproteome of SARS-CoV-2 infected human alveolar epithelial cells that overexpressed ACE2 (A549-hACE2) with or without treatment with inhibitors of G9a. Results indicated that G9a inhibition reversed the multiomic landscapes established by SARS-CoV-2 infection and from which proteins that showed G9a-dependent translation unite the networks associated with viral replication, virus-host interactions, T cell activation/proliferation, and systemic cytokine response. Inhibition of G9a suppressed SARS-CoV-2 replication, which validated our discovery of G9a-regulated translational mechanism of COVID-19 pathogenesis. Further, our correlated multiomics analysis revealed a mechanism of G9a inhibition action that showed multifaceted virus- and host-directed therapeutic effects. Because translational regulation is a precise and energy-efficient step of controlling the expression of proteins, inhibiting the G9a-mediated translation regulatory mechanism can be highly specific and effective by immediately suppressing the aberrant synthesis of COVID 19-related proteins without the need for altering transcriptional activation and mRNA processing steps.
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Xian Chen, Professor in the Dept. of Biochemistry and Biophysics, School of Medicine, University of North Carolina (UNC)-Chapel Hill, Chapel Hill, NC, United States
(Bio)
Dr. Xian Chen is a Professor in the Dept. of Biochemistry and Biophysics, School of Medicine at University of North Carolina (UNC)-Chapel Hill. He is also the Director of Technology Development at UNC Proteomic Center. Dr Chen has multi-disciplinary expertise in mass spectrometry (MS)-based proteomics and multiomics, immunology, signaling and epigenetic regulation of inflammation, proteogenomics, cancer biology, molecular and cellular biology. His pioneering work on introducing mass tags with stable isotopes, termed amino acid-coded mass tagging (AACT), a.k.a. SILAC, as a new strategy for proteomic research, was recognized in 1999 with the prestigious Presidential Early Career Award for Scientists and Engineers, the highest award in US to the scientists at their early careers. He is also the inventor of an array of functional proteomic approaches for the discovery of disease markers and new drug targets, including Chromatin-activity-based Chemoproteomics (ChaC) and ChaC-based multi-omics. Dr. Chen has a long-standing interest in understanding the molecular pathways and mechanisms underlying chronic inflammation-associated diseases such as cancer, sepsis, Alzheimers disease, diabetes, and COVID-19. In these research areas he has authored and co-authored more than 160 papers including some in high impact journals such as Nature, Science, Cell, Nature Immunology, Molecular Cell, Immunity, Cancer Discovery, Nature Cancer, Cell Reports, Science Advances, Nature Communications, Cell Chemical Biology, iScience, etc. He also holds five patents for his technology innovations and a provisional patent application for New Therapeutics for COVID-19. His H-index is at 60 with 32,440 citations.
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OA07.01 | Simultaneous Proteome Localization and Turnover (SPLAT) Analysis Reveals New Spatiotemporal Features of Unfolded Protein Responses
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Jordan Currie, University of Colorado School of Medicine, Aurora, CO, United States
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OA07.02 | Time-resolved interactome profiling to deconvolute protein quality control dynamics
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Lars Plate, Vanderbilt University, Nashville, TN, United States
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Parallel Session 08: Biomarkers and Precision Medicine
This parallel session will feature two invited presentations, followed by two selected oral abstract presentations.
Profiling Phosphoproteome Landscape in Circulating Extracellular Vesicles from Microliters of Biofluids
Many biological processes are regulated through dynamic protein phosphorylation. Monitoring disease-relevant phosphorylation events in circulating biofluids is highly appealing but also technically challenging. We introduce here a functionally tunable material and a strategy, extracellular vesicles to phosphoproteins (EVTOP), which achieves one-pot EV isolation, extraction and digestion of EV proteins, and enrichment of phosphopeptides starting with only trace amount of biofluids. The streamlined, ultra-sensitive platform enables us to quantify 500 unique EV phosphopeptides with only a few μL of plasma and over 1,200 phosphopeptides with 100 μL of cerebrospinal fluid (CSF). We demonstrated its clinical application through evaluating the outcome of chemotherapy of primary central nervous system lymphoma (PCNSL) patients with small volume of CSF, presenting a powerful tool for broad clinical applications.
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Andy Tao, Professor, Department of Biochemistry, Purdue University, West Lafayette, IN, United States
(Bio)
Prof. W. Andy Tao's group focuses on new developments in proteome analyses using systems biology approaches. He received his mass spectrometry training through his dissertation work on gas-phase chiral analysis in the Aston Lab at Purdue University, headed by Dr. R. Graham Cooks. After receiving his Ph.D. in December 2001, he became a Damon Runyon Postdoctoral Fellow in the Institute for Systems Biology at Seattle, under the supervision of Drs. Leroy Hood and Ruedi Aebersold. He started his own research group in the Department of Biochemistry at Purdue University in 2005, and currently is Professor in ranking. He also has joined appointments in the Department of Chemistry, Department of Medicinal Chemistry & Molecular Pharmacology at Purdue University.
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Can We Democratize Precision Medicine?
An underlying premise of precision medicine is that increasing the number of clinical and molecular features will improve accuracy diagnosing disease and predicting clinical outcomes (e.g., a biomarker predictive value, PPV). In other words, more is better. We propose that developing a parsimonious multi-omic model, composed of the minimal number of features able to provide similar or equal predictive performance to models produced with larger and more complex analyte compositions is required for traction in the clinical situation, especially in health care systems with economic burden. Furthermore, we propose that the features underlying a parsimonious model will represent the minimal mechanisms driving the disease outcome even in diseases with high heterogeneity in clinical manifestation. As a first test of our proposal, we analyzed 74 patients with pancreatic ductal adenocarcinoma (PDAC) obtaining >6500 features from clinical, computational pathology, and molecular (DNA, tissue RNA, tissue and plasma protein, and plasma lipid). Multiple independent machine learning models were developed and tested on curated single- and multi-omic analyte panels to determine their ability to predict clinical outcomes in patients. Interesting, the best performing multi-Omic models were comprised of different feature types even if they had equivalent PPV and accuracy for survival (0.85, 0.87, respectively), suggestive of diverse disease mechanisms achieving the same clinical outcome. The parsimonious model with 589 multi-Omic features had the same PPV while <50 features comprised of only plasma lipids and plasma protein had only slightly lower PPV. Thus, the parsimonious model is both cost effective and easily deployable in clinical practice, regardless of health care system, especially if two tier analysis is deployed with an initial plasma sample followed, if positive, by a more invasive biopsy. The adoption of remote sampling devices, where an individual can take their own blood sample and submit by mail to practitioners, could reduce barrier in medical deserts leading to broader adoption of clinical care.
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Jennifer Van Eyk, Professor of Medicine and Director of Basic Science Research, Cedars-Sinai Medical Center, Los Angeles, CA, United States
(Bio)
Dr. Van Eyk is a Professor of Medicine at Cedars-Sinai Medical Center, Director of the Basic Science Research in the Barbra Streisand Womans Hearth Center and Director of the new Advance Clinical Biosystems Institute where she recently moved from Johns Hopkins University. Most recently she has become the co-director of the Cedars Sinai Precision Health, focused on in-hospital and population individualization of health care. Dr. Van Eyk is an international leader in the area of clinical proteomics and her lab has focused the 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. Her 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.
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OA08.01 | Proteoform-reaction-monitoring (PfRM) and the discovery of biomarker candidates in liver-transplanted recipients
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Che-Fan Huang, Northwestern University, Evanston, IL, United States
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OA08.02 | Biomarker discovery in loss of TDP-43 function in frontotemporal dementia
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Andy Y. Qi, National Institute on Aging, Bethesda, MD, United States
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2:10 PM - 3:30 PM - Parallel Sessions
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Parallel Session 09: Fundamental Understanding of the Nervous System
This parallel session will feature two invited presentations, followed by two selected oral abstract presentations.
The Role of Medium Spiny Neurons in Neurodegenerative Diseases, such as Huntington's Disease and XDP Parkinsonism
Huntington’s disease (HD) is a neurodegenerative disease caused by a CAG repeat expansion in the Huntingtin (HTT) gene. The resulting polyglutamine (polyQ) tract alters the function of the HTT protein. Although HTT is expressed in different tissues, the medium spiny projection neurons (MSNs) in the striatum are particularly vulnerable in HD. Thus, we sought to define the proteome of human HD patient-derived MSNs. We differentiated HD72 induced pluripotent stem cells and isogenic controls into MSNs and carried out quantitative proteomic analysis by two approaches. First, using data-dependent acquisitions with FAIMS (FAIMS-DDA) for label-free quantification on the Orbitrap Lumos mass spectrometer, we identified 6,323 proteins with at least two unique peptides (FDR ≤ 0.01). Of these, 901 proteins were significantly altered in the HD72-MSNs, compared to isogenic controls. Second, we quantitatively validated protein candidates by comprehensive data-independent acquisitions on a TripleTOF 6600 mass spectrometer quantifying 3,106 proteins with at least two unique peptides. Functional enrichment analysis identified pathways related to the extracellular matrix, including TGF-beta regulation of extracellular matrix, epithelial-mesenchymal transition, DNA replication, senescence, cardiovascular system, organism development, regulation of cell migration and locomotion, aminoglycan glycosaminoglycan proteoglycan, growth factor stimulus and fatty acid processes. Conversely, processes associated with the downregulated proteins included neurogenesis-axogenesis, the brain-derived neurotrophic factor-signaling pathway, Ephrin-A: EphA pathway, regulation of synaptic plasticity, triglyceride homeostasis cholesterol, plasmid lipoprotein particle immune response, interferon-γ signaling, immune system major histocompatibility complex, lipid metabolism and cellular response to stimulus. Moreover, proteins involved in the formation and maintenance of axons, dendrites, and synapses (e.g., Septin protein members) are dysregulated in HD72-MSNs. Importantly, lipid metabolism pathways were altered, and we found that lipid droplets accumulated in the HD72-MSNs, suggesting a deficit in lipophagy. Our proteomics analysis of HD72-MSNs identified relevant pathways that are altered in MSNs and confirm current and new therapeutic targets for HD.
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Birgit Schilling, Professor and Director of the Mass Spectrometry Core, Buck Institute for Research on Aging, Novato, CA, United States
(Bio)
Dr. Schilling is a Professor and the Director of the Mass Spectrometry Core at the Buck Institute for Research on Aging in California, and she is also an Adjunct Professor at the University of Southern California (USC). The Schilling lab develops and implements advanced innovative protein analytical technologies (including quantitative proteomics, posttranslational modifications, protein dynamics and biomarker discovery) to advance basic biology and biomedical research related to aging research. Several research projects include investigation of protein phosphorylation, acylation, and other posttranslational modifications, as well as differential expression of proteins during disease and aging processes. We are particularly interested in deciphering underlying mechanisms of senescence during aging, and we have developed MS methodologies to quantitatively analyze protein secretomes, secreted exosomes and to perform accurate quantitative protein expression workflows. The Schilling lab has adopted several novel proteomic technologies with comprehensive and extremely sensitive quantification capabilities, and these are particularly applicable for the proposed project. We are using proteomic data-independent acquisitions (DIA), or SWATH which allows us to accurately determine changes in relative protein expression level between multiple different conditions.
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Time Resolved Metabolomics in the Brain using Sampling with LC-MS
Brain extracellular space contains a wide range of molecules including neurotransmitters, neuromodulators, and metabolites. The chemical milieu in this space is indicative of cellular activity and is involved in regulation of that activity. Samples from this space can be accessed by microdialsyis probes. Most work to date using microdialysis has focussed on measuring a small number of neurotransmitters or metabolites at a time. In this work we apply LC-MS based metabolomics approaches to monitoring the brain metabolome. Our goal is to both identify the chemicals present and begin to understand their relationship to phenotype, behaviour, drug effects, or disease state. In undirected metabolomics compounds can be identified by matching the mass spectra to a database. Often only a small fraction of the signals detected can be attributed to specific compound. For example, it is not uncommon to detect 104 “features” (signal at a given retention time and mass) but only identify a few hundred compounds. We show how deeper analysis can be performed by using advanced separations and concentrated samples. Once identified, compounds can be tracked using faster seprations for good throughput. We have identified over 300 compounds present in the brain extracellular space so far with potential for many more. We also show how directed metabolomics methods can be used to uncover chemical differences of phenotypes, in this case the HR/LR behavioural model, and relate these to differences in behavior. Finally, we describe a LC-MS based method to using stable-isotope tracing to track specific pools of glutamate as a neurotransmitter.
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Robert Kennedy, Hobart H. Willard Distinguished University Professor of Chemistry and Professor of Pharmacology, University of Michigan, Ann Arbor, MI, United States
(Bio)
Robert Kennedy is the Hobart H. Willard Distinguished University Professor of Chemistry and Professor of Pharmacology at the University of Michigan. He earned a PhD at University of North Carolina in 1988 where his work focused on using open tubular LC to analyze single cells. After a post-doc in neuroscience he started his own research program at University of Florida in 1991 before moving to University of Michigan as the Hobart H. Willard Professor of Chemistry in 2002. His research has combined his interest in biology with chemical analysis and separations. A theme of his group has been development of new chemical analysis tools that can be used at the nanoscale for several applications including screening of drugs, engineering enzymes, monitoring neurotransmitters in the brain, and studying the secretion of insulin and other hormones. His work has been recognized by several awards including the American Chemical Society Award in Chromatography, the Ralph Adams Award in Bioanalytical Chemistry, and NIH MERIT awards. He has held several service posts including Chair of the Chemistry Department at University of Michigan and is presently Associate Editor of Analytical Chemistry and ACS Measurement Science Au.
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OA09.01 | The Neuropeptide Neuroparsin-A Regulates Caretaking Behavior in Leafcutter Ants
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Michael Gilbert, University of Pennsylvania
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OA09.02 | Quantitative histone proteoform analysis of the Mus Musculus brain throughout lifespan and with life extension, spatial, and cell type specificity
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Bethany Taylor, Baylor College of Medicine, Waco, TX, United States
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Parallel Session 10: MS and Non-MS Strategies for Structural Biology
This parallel session will feature two invited presentations, followed by two selected oral abstract presentations.
Using advanced cross-linking MS to investigate the spatio-temporal distribution of long-lived proteins.
Intracellular long-lived proteins (LLPs) provide structural support for several highly stable protein complexes and assemblies that play essential roles in ensuring cellular homeostasis and function. Recently, using using in vivo dynamic metabolic stable isotope (15N) labeling of rodents, we showed that a subset of the mitochondrial proteome can persist for months in mammalian brains. Interestingly, our analysis revealed that mitochondrial LLPs (mt-LLPs) are concentrated at the inner mitochondrial membrane, specifically the sub-compartment of mitochondria called cristae. The exceptional longevity of the mt-LLPs over the course of months prompted a question of how the old and newly synthesized proteins are integrated within mitochondria and whether same peptide chains are recycled and intermixed, or spatially restricted within the organelles. To address this question, we performed a pioneering crosslinking experiments on intact mitochondria isolated from cortex and heart extracts of dynamically 15N-labeled mice. Through a combination of mitochondria immunocapture, advanced cross-linking and hybrid MS2–MS3 fragmentation approach we were able to directly probe for protein-protein interactions within old, new, and mixed mitochondrial complexes and showed that mt-LLPs are not randomly dispersed throughout individual mitochondria, but are rather spatially restricted and co-preserved for months is brains of mice.
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Ewa Bomba-Warczak, Postdoctoral Fellow , Northwestern University, Evanston, IL, United States
(Bio)
Dr. Ewa Bomba-Warczak is a neuroscientist and mitochondrial biologist investigating the lifelong fidelity of mitochondria in mammalian brains. She obtained her B.S. in Biological Sciences from the University of Illinois at Chicago, and her doctorate in Neuroscience from University of Wisconsin - Madison under the tutelage of Dr. Edwin Chapman, an HHMI Investigator. As an NINDS MOSAIC K99/R00 Scholar and ASCB Fellow in the lab of Dr. Jeffrey Savas at Northwestern University, she focuses on the application of in vivo whole rodent metabolic stable isotope pulse-chase labeling combined with proteomic mass spectrometry (MS)-based analysis to investigate the mechanisms governing the longevity of mitochondrial proteins and mtDNA.
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Matrix Landing Mass Spectrometry for 3D protein structure determination
In this presentation I will describe modifications to an Orbitrap hybrid mass spectrometer that allow for deposition of protein-protein complex cations onto transmission electron microscopy grids. These samples are then directly imaged using TEM and the three-dimensional structures of the particles solved. Here we describe the roles of the chemical matrix, the use of the mass filter for sample purification, and outline how the technique has potential to advance the exciting field of cryo-EM.
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Josh Coon, Professor of Chemistry and Biomolecular Chemistry, UW-Madison, Madison, WI, United States
(Bio)
Hailing from a small town in central Michigan, Coon escaped from the cold to earn a Ph.D. at the University of Florida. He went on to conduct his postdoctoral studies with Don Hunt at the University of Virginia. During that time he, along with Hunt and John Syka, co-invented electron transfer dissociation. In 2005 he joined the faculty at Wisconsin to start his own program. Coons research group aims to advance mass spectrometer technology to make proteome analysis faster and more accessible. Coons research in these areas has been recognized by several awards including the Biemann Medal from the American Society for Mass Spectrometry and the Ken Standing Award from the University of Manitoba. He is the Director of the NIGMS funded National Center for Quantitative Biology of Complex Systems.
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OA10.01 | Structural Elucidation of Endogenous Human Cardiac Troponin Complexes by Native Top-Down Mass Spectrometry
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Emily Chapman, University of Wisconsin - Madison, Madison, WI, United States
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OA10.02 | Global Proteome Metastability Response in Isogenic Animals to Missense Mutations and Polyglutamine Expansions in Aging
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Xiaojing Sui, Northwestern University, Chicago, IL, United States
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3:30 PM - 4:00 PM - Break
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Coffee Break and Exhibitor Viewing
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4:00 PM - 5:30 PM - Parallel Sessions
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Parallel Session 11: Metabolomics, Lipidomics, and Glycomics
This parallel session will feature two invited presentations, followed by two selected oral abstract presentations.
Protein-Protein Interactions in the Cell Glycocalyx
The glycocalyx is a highly interactive environment composed of glycans on lipids and proteins. Cell-cell interactions are mediated through the glycocalyx, however the characterization of the glycocalyx remains a considerable challenge. In this presentation, new methods for the characterization of the cell membrane will be described. We have developed enrichment methods and liquid chromatography – mass spectrometry techniques that yield the glycolipid and glycoprotein components of the cell membrane. We have employed glycosyltransferase inhibitors that allow us to modify the glycocalyx and create specific glycoforms and glycotypes. We then developed new methods for characterizing glycan-mediated protein-protein interactions. Through these tools, we explore the most comprehensive characterization of interactions in the glycocalyx.
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Carlito Lebrilla, Distinguished Professor, Department of Chemistry and Biochemistry and Molecular Medicine, University of California, Davis, Davis, CA, United States
(Bio)
Dr. Carlito B. Lebrilla is a Distinguished Professor at the University of California, Davis in the Department of Chemistry and Biochemistry and Molecular Medicine in the School of Medicine. He received his BS degree from the University of California, Irvine and Ph.D. from the University of California, Berkeley. He was an Alexander von Humboldt Fellow and a NSF-NATO Fellow at the Technical University in Berlin. He returned to the UC Irvine as a Presidents Fellow and has been at UC Davis. He has served as Chair of the Chemistry Department. His research is in Analytical Chemistry focused on mass spectrometry with applications to clinical glycomics and biofunctional food. He has over 450 peer-reviewed publications with an H-index of 95. He has co-founded several start-ups in the areas of bioactive foods and disease biomarkers. He has been awarded the Field and Franklin Medal for outstanding contributions to mass spectrometry, MCP Lectureship in Glycobiology, UCD Outstanding Researcher Award and UCD Innovator Award. He is also co-editor of Mass Spectrometry Reviews and has been on the editorial board of Molecular and Cellular Proteomics, Glycobiology, Mass Spectrometry Reviews, Journal of American Society for Mass Spectrometry, European Mass Spectrometry, and International Journal of Mass Spectrometry.
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Exploring the Molecular Universe of the Human Kidney with MALDI-MSI: From Spatial Metabolomics to Spatial Glycomics
The Kidney Precision Medicine Project (KPMP) consortium, in part, aims to create a human kidney tissue atlas from evaluating healthy and diseased biopsies. We have developed and optimized matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI)-based spatial metabolomics, lipidomics, and N-glycomics assays for analysis of human kidney biopsy tissues obtained from tissue recruitment sites (TRS) across the USA. The KPMP TRS acquire tissue from patients with varying disease states (e.g., Acute kidney injury, Chronic kidney disease, and Diabetic kidney disease). We have also linked our data to other omics-based analyses being performed within the consortium. By combining data obtained within our tissue integration site (TIS) with data from other TISs, we have begun to identify key metabolite, lipid, and N-glycan markers of cell types and disease states.
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Chris Anderton, Biogeochemical Transformations Team Lead; Mass Spectrometry Imaging Scientist, Pacific Northwest National Laboratory - PNNL, Richland, WA, United States
(Bio)
Dr. Chris Anderton is the team leader for the Biogeochemical Transformations team in PNNLs Environmental Molecular Sciences Division and the Environmental Molecular Sciences Laboratory (EMSL) user program. He has an extensive background in elucidating chemical interactions occurring across all kingdoms of life, including those within soils and the rhizosphere.
Through his graduate endeavors to his recent position, he focuses on the power of multimodal imaging methods to expand the type of information gained from samples. For his graduate work and postdoc at National Institute of Standards and Technology, he used atomic force microscopy, scanning electron microscopy, and secondary ion mass spectrometry to understand the physicochemical properties of biological samples.
At PNNL, his focus has been, in part, on expanding the mass spectrometry imaging capability within EMSLmaking these valuable tools for analyzing bacteria communities, rhizosphere-related systems, and even human health-related processes. He also focuses on visualizing the key mechanisms that drive interkingdom interactions within soil to understand the key drivers that lead to resiliency in the face of a changing environment.
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OA11.01 | Biochemical Implications of the TMEM97/ Histatin-1 Interaction
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Dominick Pierre-Jacques, University of Illinois Chicago, Chicago, IL, United States
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OA11.02 | MS-AutoQC Interactive Dashboard for Realtime Quality Control During Mass Spectrometry Data Acquisition
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Brian DeFelice, Chan Zuckerberg Biohub, Santa Clara, CA
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Parallel Session 12: Chemical Proteomics and Drug Discovery
This parallel session will feature two invited presentations, followed by two selected oral abstract presentations.
Network Systems Biology: Chemical Proteomics-Based Mapping of Macromolecular Interactions for Drug Discovery
Knowledge of protein–metabolite interactions enhances understanding of biochemical processes and facilitates drug discovery, but the generation of unbiased data is challenging. We developed a sensitive, high-throughput ligand-purification/mass spectrometry approach to map endogenous small-molecule metabolites associated with essential enzymes, putative transcription factors, and functionally-unannotated proteins in the Gram-negative bacterium, Escherichia coli. We applied structure-based computational modeling to define high-confidence ligand binding pockets, and assessed metabolic pathway relationships and evolutionary conservation to determine functional significance. The resulting interaction network includes hundreds of chemically diverse compounds including reaction substrates, products, analogs and cofactors. This ligand-interactome landscape illuminates gene function, reveals unexpected pathway crosstalk and feedback mechanisms, and suggests scaffolds for antimicrobial leads. Our approach is scalable and may be equally informative for mapping similar interactions, functional dependencies and drug design in other organisms, including human.
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Andrew Emili, Department of Biology and Department of Biochemistry, Cell Biology and Genomics, Knight Cancer Institute - Oregon Health & Science University, Portland, OR, United States
(Bio)
Prof. Andrew Emili is internationally recognized for his research in functional proteomics, interactomics and systems biology. Prof. Emilis research lab develops innovative technologies to map cellular protein interaction networks on a global-scale, publishing interactome maps of unprecedented quality, scope and resolution. He oversees a multi-disciplinary research program advancing functional proteomics technologies, including methods to profile protein-ligand networks with high resolution in model systems for both basic and translational projects.
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Post-Translational Modification Proteomics in 4D
Post-translational modifications control the structure, activity, localization, and lifetime of nearly all proteins and are often dysregulated in human disease. However, identification of post-translational modifications has far outpaced assignment of their biological functions, an endeavor that requires detailed information about where and when these modifications occur within the cell. We are integrating principles from organic chemistry, protein engineering, and mass spectrometry-based proteomics to develop innovative tools for spatially and temporally resolved mapping of protein modifications in living cells. These technologies will advance our understanding of how post-translational modifications program biological function, leading to the development of new therapeutic hypotheses for the treatment of human disease.
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Amy Weeks, Assistant Professor, University of Wisconsin-Madison, Madison, WI, United States
(Bio)
Amy Weeks is an Assistant Professor of Biochemistry at the University of Wisconsin-Madison. She received her S.B. in Chemistry from the Massachusetts Institute of Technology and earned her Ph.D. in Chemistry at the University of California, Berkeley under the mentorship of Prof. Michelle Chang. She completed postdoctoral studies in the laboratory of Prof. James Wells at the University of California, San Francisco. Her research group is focused on developing technologies for mapping the spatial organization and temporal dynamics of cellular signaling.
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OA12.01 | Deciphering the Therapeutic Accessibility of the Human Cysteineome using Experimental Quantitative Chemoproteomics
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Lisa Boatner, University of California Los Angeles, Los Angeles, CA, United States
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OA12.02 | Multiplexed kinase interactome profiling quantifies cellular network activity and plasticity
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Martin Golkowski, University of Utah
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5:30 PM - 7:00 PM - Exhibitor Mixer and Poster Session
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Evening Mixer with Exhibitors and PI-Posters
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7:00 PM - 8:30 PM - Evening Workshops
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Clinical Applications of DIA Mass Spectrometry
Data Independent Acquisition Mass Spectrometry (DIA-MS) offers a reproducible approach to unbiasedly measure hundreds to thousands of proteins in clinical sample types. The label-free nature of DIA-MS makes this approach appealing to researchers who want to sample broad swaths of the proteome from large clinical cohorts. In this workshop, experts in the field will weigh in on best practices to qualify DIA-MS proteomic methods for clinical use and strategies to make quantitation in DIA-MS based methods more robust including utilizing matrix matched calibration curves and establishing robust filtering criteria for datasets. Examples of how DIA-MS is being used for clinical and drug development applications including monitoring health status of patients and measurement of candidate pharmacodynamic biomarkers to support drug development will be presented. The expert panel will also discuss data analysis challenges associated with processing large DIA-MS datasets and suggest various options for software tools to efficiently search and quantify proteins.methods. The goal of this workshop is to look behind the curtain with experts focusing in each respective modern data acquisition method and answer the tough questions. How confident are you in that identification or intensity value? How do you make those cutoffs? How do you dig into your data to make sure when everything is on the line?
Presented By:
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Veronica Anania, Genentech
(Bio)
Veronica Anania, PhD. is a Senior Principal Scientist and Director of the Biomarker Mass Spectrometry Group within the Department of Translational Medicine at Genentech. Her laboratory utilizes mass spectrometry approaches to enable biomarker hypothesis testing in the context of clinical trials. Her research aims to develop state-of-the-art targeted MS and DIA-MS approaches to enable measurement of pharmacodynamic analytes in a broad range of clinical matrices in order to identify early biomarkers reflective of proof of activity for investigational new drugs. Results from these studies support forward and reverse translation efforts and inform clinical biomarker strategies in key therapeutic areas including inflammatory bowel disease, multiple sclerosis, lupus, fibrosis, and Alzheimers Disease.
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Human Glycoproteomics Initiative Workshop on Glycoproteomics and Glycoinformatics
This workshop organized by the Human Glycoproteomics Initiative (HGI, https://www.hupo.org/Human-Glycoproteomics-Initiative) under the HUPO B/D Human Proteome Project seeks to bring together thought leaders and users in glycoproteomics as well as general proteomics scientists with an interest in glycoanalytics to discuss the latest technology and informatics developments in the field. The workshop strategically places a focus on new methods for the MS-based generation and software-driven analysis of large-scale glycopeptide data that remain current bottlenecks in glycoproteomics. The workshop also explores how such advances can be leveraged to improve our insight into the immensely complex and dynamic human glycoproteome and ultimately translate into improved glycobiological knowledge and clinically useful products.
Presented By:
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Nicholas Riley, Postdoctoral Scholar, Chemistry, Stanford University, Stanford, California, United States
(Bio)
Nick Riley is a K99 postdoctoral fellow in 2022 Chemistry Nobel Laureate Prof. Carolyn Bertozzi's lab at Stanford University, and he will start as an assistant professor of Chemistry at the University of Washington in summer 2023. He received his B.S. in Chemistry and Psychology from the University of South Carolina with Honors from the South Carolina Honors College and earned his Ph.D. in Chemistry at the University of Wisconsin-Madison under the mentorship of Prof. Joshua Coon. His research centers around developing mass spectrometry-based technologies for studying extracellular and cell surface biology, with a special focus on glycosylation and the glycoproteome
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7:00 PM - 8:00 PM - ECR Networking Event
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ECR Speed Dating Elevator Pitches
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8:00 PM - 9:00 PM - ECR Networking Event
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ECR Town Hall
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