7:30 AM - 7:00 PM - Registration
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Registration and Information Desk
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8:00 AM - 8:30 AM - Break
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Morning Coffee
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8:30 AM - 9:05 AM - Plenary Session
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Robert J. Cotter New Investigator Award Plenary Session
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9:05 AM - 9:35 AM - Break
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Coffee Break
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9:35 AM - 10:55 AM - Parallel Sessions
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Parallel Session 07: Post-Translational Modifications to Proteoforms
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Luca Fornelli, University of Oklahoma, Norman, OK, United States
(Bio)
Dr. Luca Fornelli earned both his B.Sc. and M.Sc. in Biotechnology from the University of Padova, Italy. He received his PhD under the supervision of Dr. Yury Tsybin at the École Polytechnique Fédérale de Lausanne, Switzerland, with a thesis focused on the characterization of antibodies by middle-down and top-down mass spectrometry. He later obtained a postdoctoral fellowship from the Swiss National Science Foundation and joined the research group of Dr. Neil Kelleher at Northwestern University. Since 2019 Dr. Fornelli works as an Assistant Professor at the University of Oklahoma, where he develops new methods for top-down proteomics. He has been nominated "Emerging Investigator" by the Journal of the American Society for Mass Spectrometry in 2021, and received the ASMS Research Award in the same year. He is also the recipient of the 2022 BBA Rising Star Award.
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Site-Directed Photodissociation for Rational Dissection of Intact Proteins
Current dissociation methods for characterizing proteins in top-down experiments yield fragments in a highly stochastic fashion and afford little control over the location or number of dissociation events. Dissociation is also strongly dependent on molecular size and charge state. It doesn’t have to be that way. A new method for dissociating proteins will be presented. The underlying mechanism for dissociation has not been previously observed and affords a high degree of spatial control over the location where dissociation takes place. The experiment can be easily implemented with 266nm laser in a single photodissociation step following quantitative and simple modification of the protein. This new dissociation methodology will enable several new classes of experiments in top-down that were previously not feasible.
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Ryan Julian, UC Riverside, Riverside, CA, United States
(Bio)
Ryan Julian is a professor of Chemistry at the University of California, Riverside, where he leads a mass spectrometry research group. Dr. Julian obtained his PhD in 2003 at Caltech under the guidance of Jack Beauchamp, focusing on a variety of molecular recognition and ion chemistry projects. He pursued postdoctoral training for two years focused on instrumentation and ion mobility with David Clemmer and Martin Jarrold at Indiana University. Since 2005 in his own lab at UCR, research interests have spanned a broad range of subjects including gas-phase ion chemistry, radical-directed dissociation, antioxidant capacity, and the development of a variety of MS-based structural tools. Most recently, a particular interest in the study of isomerization in long-lived proteins and how these modifications relate to age-related diseases has become a major focus.
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Parallel Session 08: Translational Approaches: Cancer, Neurodegeneration, and Cardiovascular Diseases
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11:00 AM - 12:00 PM - Lightning Session
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Lightning Talks - Round 02
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1:30 PM - 3:00 PM - Poster Session
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Poster Session 02 and Exhibitor Viewing
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3:00 PM - 4:20 PM - Parallel Sessions
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Parallel Session 09: Biomarkers and Precision Medicine
A Scaled Proteomic Discovery Study for Prostate Cancer Diagnostic Signatures Using Proteograph Workflow with Trapped Ion Mobility Mass Spectrometry
Purpose: The low cancer specificity of Prostate-Specific Antigen (PSA), the principal blood biomarker for prostate cancer detection, leads to a high frequency of unwarranted prostate biopsies. To alleviate this deficit, we executed a proteomic discovery study seeking PSA reflex signatures using the Proteograph™ Product Suite, a multi-nanoparticle-based deep plasma/serum proteomics workflow (Seer, Inc.), with timsTOF Pro mass spectrometry (Bruker) to interrogate over 900 serum specimens from patients referred for biopsy based on elevated PSA and/or abnormal digital rectal exam.
Methods: Our study followed rigorous design principles including uniform collection, randomization and blinding of specimens, all of which were processed with the Proteograph Product Suite. Liquid chromatography-mass spectrometry (LC-MS) analyses leveraged the Bruker timsTOF Pro MS platform utilizing 30-minute reversed-phase chromatography and a label-free dia-PASEF (data independent acquisition - parallel accumulation serial fragmentation) data acquisition method. Peptides deriving from a chosen subset of specimens designed to maximize peptide diversity were pooled, fractionated and analyzed using DDA (data-dependent acquisition)-PASEF to build a spectral reference library.
Results: The DIA-NN algorithm was employed through the cloud-based Proteograph Analysis Suite (PAS) to search LC-MS data. Leveraging our study-specific spectral library proteomic depth achieved was approximately 3600 protein groups identified (median) per patient serum specimen and more than 4400 in at least 25% of samples across the study. Customized machine learning workflows and the SeerML pipeline were used to identify and assess diagnostic power of new proteomic signatures.
Conclusions: Our data demonstrate the remarkable proteomic depth achievable in a scaled patient serum specimen discovery study using a combination of Proteograph and timsTOF platforms. This significant effort revealed serum proteomic signatures with increased diagnostic performance over that provided by PSA blood measurement and traditional patient-associated metadata alone, providing a foundation for future clinical tests aimed to reduce the current high frequency of unnecessary prostate biopsy.
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Mark Flory, Oregon Health and Science University, Portland, OR, United States
(Bio)
Mark Flory is a Senior Research Scientist at Oregon Health and Science University (OHSU) in Portland and is specifically positioned in the Cancer Early Detection Advanced Research Center (CEDAR) of OHSU's Knight Cancer Institute. Mark received his Ph.D. in Molecular and Cellular Biology at the University of Washington working in Trisha Davis' group, and subsequently trained on proteomic mass spectrometry in Ruedi Aebersold's group at the Seattle Institute for Systems Biology. Mark has since enjoyed professional positions spanning the academic and biotech sectors including work with Parag Mallick in the Canary Center at Stanford for Early Cancer Detection. At OHSU Mark now focuses on implementing powerful proteomic technologies, including Seer Proteograph and Bruker timsTOF mass spectrometry, to facilitate biomarker discovery aimed at uncovering clinically actionable signatures for early cancer detection and to gain new insights into mechanisms underlying disease progression.
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Parallel Session 10: Chemical Proteomics and Drug Discovery
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Keriann Backus, UCLA, Los Angeles, CA, United States
(Bio)
Keriann Backus is an Assistant Professor of Biological Chemistry and Chemistry and Biochemistry at the University of California, Los Angeles. Her research interests include the developing of new chemical probes, chemoproteomic and proteogenomic methods to study and rewire protein function in health and disease.
Dr. Backus received a BS in Chemistry and BA in Latin American Studies in 2007 from Brown University. Her doctoral research was conducted in the laboratories of Benjamin Davis (Oxford) and Clifton Barry (NIH, NIAID) as a 2007 Rhodes Scholar and an NIH Oxford Cambridge Scholar. Her PhD work focused on the development of chemical probes to label and image Mycobacterium tuberculosis. In 2012, Backus completed her doctorate and began an NIH postdoctoral fellowship at The Scripps Research Institute in the laboratory of Benjamin Cravatt. Her postdoctoral research developed chemoproteomic methods for the proteome-wide identification of ligandable cysteine and lysine residues. At UCLA, Dr. Backus's research has been recognized by numerous awards, including a Beckman Young Investigator, DARPA Young Faculty Award, a V Scholar Research Award, Packard Fellowship, NIH New Innovator Award, and Ono Breakthrough Science Initiative Award.
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Proteome-Wide Ligand and Target Discovery in Cells
Advances in DNA sequencing and editing technologies have revolutionized our understanding of the molecular basis of many human diseases. However, many disease-relevant genes encode proteins that are poorly characterized and/or are considered “undruggable”, hindering our understanding of disease mechanisms and translating this knowledge into new therapies. Chemical probes offer a valuable way to directly interrogate the function and disease-relevance of proteins and can also serve as valuable leads for drug development, yet most proteins in the human proteome lack small-molecule ligands that can serve as probes. More generally, the boundaries, if any, on the ligandability, and therefore potential druggability, across native proteomes remains poorly understood. In this seminar, I will describe our lab’s efforts to develop powerful chemical proteomic strategies to broadly map ligandable proteins directly in cells, and how this information can be advanced into useful chemical probes to investigate protein function.
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Christopher Parker, Associate Professor, The Scripps Research Institute, San Diego, CA, United States
(Bio)
Chris is an Associate Professor in the Department of Chemistry at Scripps Research. His lab's research focuses on employing chemoproteomic platforms to develop useful small molecules to modulate complex biological processes and illuminate mechanisms of disease, such as cancer and immune conditions. Chris obtained his B.S. in Chemistry at Case Western University in 2007 and his Ph.D. in Chemistry at Yale University in 2013 under the guidance of Professor David Spiegel. He performed postdoctoral work as an American Cancer Society fellow at Scripps Research with Professor Ben Cravatt, and in 2018 he joined the faculty.
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4:30 PM - 5:50 PM - Parallel Sessions
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Parallel Session 11: Multiplexed and Spatial Imaging Omics
Quantifying Therapeutic Efficacy with Novel Fluorescence Imaging
Deregulation of kinase function in cell signaling pathways is implicated in numerous cancers. In response, kinase inhibitors (KIs) have been developed to interact with these kinases for highly specific treatment. Though nearly 50 KIs have been FDA-approved, KI monotherapy is seldom curative, likely owing to tumor heterogeneity and acquired resistance. In response, effective combination therapies must be tailored to known resistance mechanisms to efficiently engage with their targets and exploit cellular vulnerabilities. However, standard drug screening tools (e.g., plasma analysis, western blot) are bulk in nature, and no established technology exists to quantify KI target engagement, concomitant with local protein expression, while assessing tumor response heterogeneity. To address these shortcomings, our group has (1) developed protocols to fluorescently label KIs (and other small molecule therapeutics) that mimic the native drug, (2) advanced a novel intracellular paired agent imaging (iPAI) platform to quantify drug target availability (DTA) with these fluorescent KIs, and (3) established and validated a highly multiplexed immunostaining strategy utilizing DNA barcoded antibodies, enabling in situ cyclic immunofluorescence (cyCIF) imaging. In this project, we combine these three complementary innovations into a fluorescence imaging platform we call TRIPODD (Therapeutic Response Imaging through Proteomics and Optical Drug Distribution and binding).Deregulation of kinase function in cell signaling pathways is implicated in numerous cancers. In response, kinase inhibitors (KIs) have been developed to interact with these kinases for highly specific treatment. Though nearly 50 KIs have been FDA-approved, KI monotherapy is seldom curative, likely owing to tumor heterogeneity and acquired resistance. In response, effective combination therapies must be tailored to known resistance mechanisms to efficiently engage with their targets and exploit cellular vulnerabilities. However, standard drug screening tools (e.g., plasma analysis, western blot) are bulk in nature, and no established technology exists to quantify KI target engagement, concomitant with local protein expression, while assessing tumor response heterogeneity. To address these shortcomings, our group has (1) developed protocols to fluorescently label KIs (and other small molecule therapeutics) that mimic the native drug, (2) advanced a novel intracellular paired agent imaging (iPAI) platform to quantify drug target availability (DTA) with these fluorescent KIs, and (3) established and validated a highly multiplexed immunostaining strategy utilizing DNA barcoded antibodies, enabling in situ cyclic immunofluorescence (cyCIF) imaging. In this project, we combine these three complementary innovations into a fluorescence imaging platform we call TRIPODD (Therapeutic Response Imaging through Proteomics and Optical Drug Distribution and binding).
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Summer Gibbs, Oregon Health and Science University, Portland, OR, United States
(Bio)
Dr. Summer Gibbs has 20 years of experience in the field of molecular imaging with expertise in fluorescent contrast agent development and its clinical translation as well as single cell fluorescence imaging technologies. She completed her Ph.D. in Biomedical Engineering under the direction of Brian Pogue, Ph.D. at the Thayer School of Engineering at Dartmouth College in 2008. She joined Dr. John Frangioni's Laboratory for her postdoctoral training where she completed three years of postdoctoral training and was promoted to Instructor in Medicine. She joined the faculty in the Biomedical Engineering Department at Oregon Health and Science University (OHSU) as an Assistant Professor in June 2012 and was promoted to Professor in July 2022. The current focus of her laboratory is on the development of novel fluorescent probes and fluorescence imaging technologies to improved macroscopic and microscopic patient-specific imaging.
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Metabolome-Informed Proteome Imaging of Complex Biological Systems
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Kristin Burnum-Johnson, Richland, WA, United States
(Bio)
Dr. Kristin Burnum-Johnson is a Senior Scientist and Team Lead of the Environmental Molecular Sciences Laboratory's Metabolomics group at Pacific Northwest National Laboratory (PNNL). Kristin earned her Ph.D. in Biochemistry from Vanderbilt University with Prof. Richard M. Caprioli, and then completed a postdoctoral fellowship at PNNL with Dr. Richard D. Smith. She was selected to receive a 2019 Early Career Research Program award from the U.S. Department of Energy Office of Science. Her research program is dedicated to characterizing the molecular landscape of heterogeneous samples using novel mass spectrometry approaches to address specific biological, medical, and environmental research questions.
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Parallel Session 12: Functional Characterization of the Proteome
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Tianhao Yu, The University of Illinois at Urbana-Champaign, Champaign, IL, United States
(Bio)
Tianhao Yu is currently a Ph.D. candidate in the Chemical and Biomolecular Engineering department at University of Illinois at Urbana Champaign under the supervision of Dr. Huimin Zhao. Tianhao received his B.S. in Chemical engineering from University of Rochester in 2019. His research focuses on applying machine Learning to address various topics in the field of synthetic biology. During his Ph.D. training, he has published several peer-reviewed research articles and reviews in top-tier journals such as Science and Nature Catalysis. He is the recipient of Mavis future faculty fellowship and Glenn E. and Barbara R. Ullyot Graduate Fellowship.
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Nick Riley, University of Washington, Seattle, WA, United States
(Bio)
Nicholas M. Riley is an Assistant Professor of Chemistry at the University of Washington. He completed his ACS Certified B.S. degree in Chemistry from the University of South Carolina in 2012 with Honors from the South Carolina Honors College, and he earned his Ph.D. in chemistry in 2018 while working on electron-transfer dissociation-centric methodology in the research group of Prof. Joshua J. Coon at the University of Wisconsin-Madison. He then was an NIH K00 and K99 postdoctoral fellow with 2022 Nobel Laureate in Chemistry Prof. Carolyn R. Bertozzi at Stanford University, where he focused on MS-based glycoproteomics and chemical glycobiology. His research program at UW is focused on innovative bioanalytical and chemical biology technologies to investigate essential principles of glycocode regulation and dysregulation.
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6:00 PM - 7:30 PM - ECR Networking Event
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ECR Evening Event
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6:00 PM - 7:30 PM - Evening Workshops
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Evening Workshop
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7:30 PM - 9:00 PM - Exhibitor Mixer and Poster Session
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Evening Mixer with Exhibitors
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