January 2021 Virtual Meeting

Speaker: Shao-En Ong, University of Washington

Topic: Kinome analyses for pharmacoproteomics

Date: Tuesday, January 19th, 2021

Time: 2:00 PM Presentation

Location: Webinar – see emails on Jan. 8 and 15 for invite link. Join the mailing list

Abstract: With few targeted therapies for genetic alterations in cancer, pharmacogenomics has been used to link genetic features with drug response. Because proteomics allows sensitive and direct measurements of cellular signaling pathways, we developed a novel pharmacoproteomics platform to identify kinase pathways correlating with drug response by combining kinobead-based activity profiling of 346 kinases and high-throughput screening of 299 kinase inhibitors in 17 hepatocellular carcinoma (HCC) cell lines. We identified novel kinases involved in drug resistance, that upon small molecule inhibition or genetic knockdown, rewired cellular signaling and restored chemosensitivity. We applied kinobead-MS in clinical HCC samples to identify signatures of drug sensitivity common to cell lines and patient tumors. Our broadly applicable approach identifies kinome features responsible for the activity of individual drugs and provides a resource for biomarker discovery and target deconvolution.

December 2020 Virtual Meeting

Speaker: Perry Wang, US Food and Drug Administration

Topic: Advanced Application of LC-MS and Challenges

Date: Monday, December 14th, 2020

Time: 2:00 pm Presentation

Location: Webinar – see emails on Dec. 3 and 10 for invite link. Join the mailing list

Abstract: Liquid chromatography-mass spectrometry (LC-MS) is the most sensitive analytical technique by far. It combines the physical separation power of liquid chromatography with the mass analysis capabilities of mass spectrometry. Because the individual capabilities of each technique are synergistically enhanced, the combination of liquid chromatography with mass spectrometry could be called a “perfect marriage” -liquid chromatography separates components in mixtures by affinity and mass spectrometry differentiates the components by mass. Therefore, LC-MS is applied in a broad field including biotechnology, environment monitoring, food safety, and pharmaceutical, agrochemical, and cosmetic industries. However, the technique often faces a great challenge -matrix effect, which can be observed as either a loss (ion suppression), or an increase (ion enhancement) in responses. The matrix effects affect the detection capability, precision and/or accuracy for the analytes of interest. Thus, the matrix effects should be evaluated during method development by comparing the response of a standard solution prepared in a sample matrix over the response in neat solutions or comparing the calibration-curve slope of standard solutions prepared in sample matrix over the slope of standards prepared in neat solutions. Unfortunately, a representative matrix is not always available for some studies, and how to evaluate and minimize the matrix effects are challenging. Different techniques to minimize matrix effects will be presented and the concept of matrix effect factor (MEF) will be introduced and discussed.

November 2020 Virtual Meeting

Speaker: Yansheng Liu, Yale University School of Medicine

Topic: DIA-MS and Its Application to Profiling Cellular Proteome and Proteoform Dynamics

Date: Monday, November 16th, 2020

Time: 2:00 pm Presentation

Location: Webinar – see emails on Nov. 5 and 12 for invite link. Join the mailing list

Abstract: The term ‘proteoform’ is now used to designate different molecular forms in which the protein product of a single gene can be found, including changes due to genetic variations, alternatively spliced RNA transcripts, and post-translational modifications. Although proteoform is normally studied by the top-down approach, we will discuss a new bottom-up strategy to investigate the site-specific modiforms. We will first review the data-independent acquisition mass spectrometry (DIA-MS) and its development in our group. We will then present how we use DIA-MS, pulse stable isotope-labeled amino acids in cells (pSILAC) approach, and genome-wide correlation analysis for quantifying both abundance and turnover rate of proteins in cancer cell models.

September 2020 Virtual Meeting

Speaker: Joe Cannon, Merck

Topic: Simplifying Cyclic Peptide Hydrolysis Interpretation in Metabolite Identification

Date: Monday, September 21st, 2020

Time: 1:00 pm Presentation

Location: Webinar – see emails on Sept. 10 and 18 for invite link. Join the mailing list

Abstract: Peptides, as therapeutics, can be used to disrupt crucial protein-protein interactions in disease states. As a modality, they offer an exciting compromise between large molecule-like specificity and small molecule-like absorption and distribution, all without the need for orthosteric binding. Despite these favorable properties, peptides suffer from short in vivo half-life due to protease mediated hydrolysis. To combat this, peptides are often conjugated and internally crosslinked to enhance rigidity or cyclized to decrease susceptibility to amino and carboxypeptidases. For linear peptides, identifying the site of hydrolysis is simple and similar to peptide identification in proteomics experiments. For cyclized peptides, it is very challenging due to the fact that hydrolysis simply linearizes the molecule, and the mass of a peptide from hydrolysis at one position is isobaric with every other position. 2-pyridine carboxaldehyde (2PCA) is used here to selectively conjugate the N-terminal amino acid and provide an amino acid specific low mass reporter fragment ion doublet that points to the site of hydrolysis. The chemistry is demonstrated here on a HeLa tryptic digest and proof-of-concept studies are shown on cyclic peptides.

June 2020 Virtual Meeting

Topic: Post-ASMS Virtual Poster Night and ASMS Travel Award Presentations

Date: Monday, June 22nd, 2020

Time: Poster listing online; 1:00 pm Presentations (Zoom link in June 11, 19 email)

ASMS Travel Award Recipients:

    • Gessica Vasconcelos, George Washington University

: “Fiber-based laser ablation electrospray ionization mass spectrometry for molecular profiling and metabolite gradients in anatomical regions selected by fluorescence microscopy”

    • Kunyu Zheng, Georgetown University

: “Non-targeted detection of fluorinated compounds using dielectric barrier discharge nano-electrospray ionization”

    • Yulemni Morel, Univ. of Maryland School of Pharmacy

: “Integrating Qual/Quan Workflows for Combined Structure Characterization and Quantitation of Vinyl Ether Phosphatidylethanolamine”

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WBMSDG attendees are invited to submit their posters for an online listing in lieu of an in-person poster night. Submit yours via the form below!

MP 031 Non-proximate Ambient Sampling for Solvent-free Analysis of Intact Objects; G. Asher Newsome1; Kathleen Martin2; Julia Campbell-Such3; 1Smithsonian Museum Conservation Institute, Suitland, MD; 2Smithsonian National Museum of the American Indian, Hillcrest Heights, MD; 3Smithsonian National Museum of African Art, Washington, DC

MP 206 Optimization of a targeted, multi-allergen LC-MS/MS method for the quantification of egg, milk, and peanut in food; Weili Xiong1; Christine H. Parker1; Katherine L. Fiedler1; 1U.S. Food and Drug Administration, Center for Food Safety and Applied Nutrition, College Park, MD

MP 296 The Inelasticity of Ion-Molecule Collisions in Ion Mobility Spectrometry, Glenn Spangler, Technispan LLC

MP 355 Hepatic dyslipidemia in little brown bats (Myotis lucifugus) and big brown bats (Eptesicus fuscus) with white nose syndrome; Evan L. Pannkuk1; Nicole A. S.-Y. Dorville2; Yvoone A. Dzal2; Quinn E. Fletcher2; Kaleigh J. O. Norquay2; Craig K. R. Willis2; Albert J. Fornace Jr.1,3; Evagelia C. Laiakis1,3; 1Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC; 2Department of Biology, University of Winnipeg, Winnipeg, MB; 3Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC

TP 265 Enhanced Ionization and Facile Selection of Ions at Atmospheric-pressure by Perturbation-induced Pulsing of nano-ESI Coupled to a Single Ion Gate; William McMahon and Kaveh Jorabchi; Department of Chemistry, Georgetown University, Washington, DC

TP 516 Measuring protein conformational change in living cells by quantitative, comprehensive, and ultra-sensitive protein footprinting. Jenna G. Caldwell1*, Bjorn-Erik Wulff1, Lichao Zhang2, Joshua E. Elias2, Pehr A.B. Harbury2. 1Department of Biochemistry, Stanford School of Medicine, Stanford, CA; 2Chan Zuckerberg Biohub, Stanford, CA

WP 020 Identification approaches of the efflorescence detected in Infinity of Nations at the Smithsonian National Museum of the American Indian; Alba Alvarez-Martin* [1]; John George [2]; Emily Kaplan [2]; Lauren Osmond [2]; Leah Bright [2]; G. Asher Newsome [1]; Gwénaëlle Kavich [1]; Rachel Kaczkowski [1]; Susan Heald [2]. [1] Museum Conservation Institute, Smithsonian Institution, Suitland, MD; [2] The National Museum of the American Indian, Smithsonian Institution, Washington, DC

WP 462 Mass Spectrometric Approaches for the Structural Characterization of Chemically Targeted PreQ1 Riboswitches; Christopher C. Lai1; Desta D. Bume1; John S. Schneekloth, Jr.1; James A. Kelley1. 1Chemical Biology Laboratory, Center for Cancer Research, NCI-Frederick, National Institutes of Health, Frederick, MD

ThP 279 Trypsin – a Tired Workhorse? The Selectivity of Atypical Cleavages by Trypsin; Meghan Burke1; Yuxue Liang1; Stephen E. Stein1; 1National Institute of Standards and Technology, Gaithersburg, Maryland