February Meeting

Speaker: Joshua Coon, University of Wisconsin-Madison

Topic: From Systems to Structural Biology – new MS technology to drive discovery

Date: Wednesday February 28, 2024

Time: 6:15 pm Dinner, 7:15 pm Presentation

Location: University of Maryland (Lecture Hall CHM 1402 Directions)

Dinner: Please RSVP to Jonathan Ferguson (jonathan.ferguson33@gmail.com) by Monday, February 26 if you will be attending the dinner.

Abstract: In this presentation I will provide several examples of how MS technology can drive biological discovery. First, we use a high-throughput proteomic, metabolomic, and lipidomic methodology to profile nearly 1,000 human cell lines that each are missing a mitochondrial gene. Then, using computation and informatics, we combine this dataset to discovery the functions of several genes, linking two of them directly to human disease. Next, we use multiple proteases and extensive MS to provide the deepest coverage and analysis of the human proteome to date – confirming that the majority of spliced RNA molecules do indeed get converted into proteins. Next, we describe use of the Orbitrap Astral hybrid to profile human proteomes in under one hour, profile human plasma at a depth of nearly 7,000 proteins, and measure protein phosphorylation at unprecedented depth and speed. Finally, we present on a modified Orbitrap mass spectrometer that is used to prepared samples for cryoEM. Briefly, protein-protein complexes are ionized using native ESI and then either mass analyzed or landed onto a cryogenically cool EM grid within the MS system. Water vapor is introduced to cover the landed particles with amorphous ice. Following landing, the samples are removed from vacuum and placed in a cryoEM instrument for direct imaging.

January Meeting

Speaker: Keenan Walker, National institute on Aging, NIH

Topic: Biomarkers and Peripheral Drivers of Dementia Identified Using Plasma Proteomics

Date: January 22, 2024

Time: 6:15 pm Dinner, 7:15 pm Presentation

Location: Shimadzu Scientific Instrument, Inc. Training Center 7100 Riverwood Drive, Columbia, MD 21046 (Directions)

Dinner: Please RSVP to Jonathan Ferguson (jonathan.ferguson33@gmail.com) by Friday, January 19 if you will be attending the dinner.

Abstract: Recent advances in high-throughput technology for the characterization of the human proteome have enabled the simultaneous assessment of thousands of circulating proteins at scale. Using this technology to examine plasma proteomic changes that precede the onset of dementia and Alzheimer’s disease may provide a window into the underlying disease biology and nominate new biomarkers and targets for intervention. By applying SomaLogic’s SomaScan Assay to conduct a large-scale prospective analysis of the plasma proteome in cognitively normal individuals who later progress to dementia, we take a data-driven approach to discovery of early-stage blood-based biomarkers for Alzheimer’s disease, dementia, and cerebral small vessel disease. Through multi-cohort efforts which leverage network-based proteomics, genetics, brain imaging, and cerebral spinal fluid (CSF) biomarkers, we have identified a novel set of proteins, protein networks, and related biological pathways that may play a mechanistic role in age-related neurodegenerative conditions, including Alzheimer’s disease and vascular cognitive impairment.
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lightning talks
Noah Smeriglio (George Washington University)
Yingwei Hu (Johns Hopkins University)

December Meeting

Speaker: Dingyin Tao, National Center for Advancing Translational Sciences, NIH

Topic: From Mass Spectrometry-Based Proteomics to Patient Care

Date: December 11, 2023

Time: 6:15 pm Dinner, 7:15 pm Presentation

Location: Shimadzu Scientific Instrument, Inc. Training Center 7100 Riverwood Drive, Columbia, MD 21046 (Directions)

Dinner: Please RSVP to Jonathan Ferguson (jonathan.ferguson33@gmail.com) by Friday, December 8 if you will be attending the dinner.

Abstract: Mass spectrometry-based proteomics plays a vital role in various stages of translational science, e.g. biomarker discovery and drug target identification. I will discuss these two separate cases: the first part focuses on the discovery of 35 parasite markers from which we selected a single candidate for use in a point-of-need (PON) rapid diagnostic test. We performed a cross-sectional, multi-omics study of saliva from 364 children with subclinical infection in Cameroon and Zambia, and produced a prototype saliva-based PON lateral flow immunoassay test for P. falciparum gametocyte carriers. This assay is being commercialized by a company founded in South Africa. The second part focuses on a new drug target for an old drug, Auranofin. UBA1 is the primary E1 ubiquitin-activating enzyme responsible for generation of activated ubiquitin required for ubiquitination, a process that regulates stability and function of numerous proteins. Abnormal UBA1 activity or ubiquitination causes or drives many human diseases, such as cancer, major neurodegenerative diseases, Angelman syndrome, VEXAS syndrome, and spinal muscular atrophy, as well as aging, highlighting the importance of the discovery of small molecule modulators of UBA1 activity for research and therapeutic purposes. Auranofin, a drug approved for the treatment of rheumatoid arthritis, was found in our high-throughput compound screen assay. Furthermore, HPLC-MS/MS was used to identify UBA1 as the new drug target of Auranofin. Through proteomics analysis, it was confirmed that auranofin binds to UBA1’s ubiquitin fold domain and conjugates to the Cys 1039 residue. This binding enhances interactions of UBA1 with at least 20 different E2 ubiquitin-conjugating enzymes, facilitating ubiquitin charging to E2 and increasing the activities of seven representative E3s in vitro. Auranofin promotes ubiquitination and degradation of misfolded ER proteins during ER-associated degradation in cells at low nanomolar concentrations. It also facilitates outer mitochondrial membrane-associated degradation. These findings suggest auranofin can serve as a much-needed tool for UBA1 research and therapeutic exploration.
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WBMSDG is including a lightning talk before the main talk at each event. Each lightning talk lasts 7 minutes with no more than 5 slides, and 5 minutes for Q&A. The desired speakers are early-career researchers/scientists in mass spec-related areas. They can be junior scientists, postdoctoral fellows, graduate or undergraduate students.

Please submit abstracts to co-chairs to apply for the lightning talks, and our board members will review the abstracts on a rolling basis.

Structure the abstract (maximum 300 words) with the following headings:
Title (maximum 20 words)
Authors and affiliations (Including senior authors/PIs)
Introduction
Methods
Results
Conclusions