Memorial Symposium in Honor of Dr. Andrew J. Alpert

Sept. 13-15, 2023, Zoom

It is with heavy hearts and profound respect that we announce this memorial symposium to honor the life and legacy of the esteemed Dr. Andrew J. Alpert. Dr. Alpert is a brilliant scientist, a dedicated mentor, a devoted collaborator, and a legend in the field of chromatography. Dr. Alpert’s significant contributions left an indelible mark on the world of chromatography! Andy is a very kind person! Andy touched the lives of so many, he was always willing to stop what he was doing and help others. Dr. Alpert was also a talented artist, linguist (four languages), musician (pianist), sportsman (pole vaulter), chef, naturalist, and above all – a beloved husband, father, brother, and grandfather to five grandchildren.

The symposium will feature distinguished speakers, colleagues, and friends together with his family members to celebrate his legacy by highlighting the extraordinary contributions he made to the field of chromatography and mass spectrometry-based proteomics as well as the personal connections he forged throughout his life. In addition to the speakers, there will be opportunities for attendees to participate in the virtual receptions and pay their respects through heartfelt tributes. The symposium aims to foster an atmosphere of intellectual exchange, inspiration, and remembrance, just as Dr. Alpert did throughout his distinguished career.

The conference website is now available: https://labs.wisc.edu/aams/. Please register at your earliest convenience. Registration is free but required. Everyone is welcome. Let us come together to celebrate the life and legacy of Dr. Andrew J. Alpert!

With deepest respect,
Organizers (CACA, PolyLC, Inc, 仪器信息网, and Ge Research Group)

September 2023 Meeting and Vendor Night

Speaker: John R. Yates, The Scripps Research Institute

Topic: How a single mutation in CFTR causes the systemic disease cystic fibrosis: interactions, PTMs, and structure

Date: Monday, September 11, 2023

Time: 6:00 pm Dinner and Vendor Night, 7:15 pm Presentation

Location: Shimadzu Scientific Instrument, Inc. Training Center 7100 Riverwood Drive, Columbia, MD 21046 (Directions) This will be an in-person meeting.

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

Abstract: Protein conformation is dynamic as it is influenced by post-translational modifications (PTMs) and interactions with other proteins, small molecules or RNA, for example. However, in vivo characterization of protein structures and protein structural changes after perturbation is a major challenge. Therefore, experiments to characterize protein structures are typically performed in vitro and with highly purified proteins or protein
complexes, revealing a static picture of the protein. To identify the true conformational space occupied by proteins in vivo, we developed a novel low-resolution method named Covalent Protein Painting (CPP) that allows the characterization of protein conformations in vivo. Here, we report how an ion channel, the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), is conformationally changed during biogenesis and channel opening in the cell. Our study led to the identification of a novel opening mechanism for CFTR by revealing that the interaction of the intracellular loop 2 (ICL2) with the nucleotide binding domain 2 (NDB2) of CFTR is needed for channel gating, and this interaction occurs concomitantly with changes to the narrow part of the pore and the walker A lysine in NBD1 for wt CFTR. However, the ICL2:NBD2 interface, which forms a “ball-in-a-socket” motif, is uncoupled during biogenesis, likely to prevent inadvertent channel activation during transport. Mutation of K273 in the ICL2 loop severely impaired CFTR biogenesis and led to accumulation of CFTR in the Golgi and TGN. CPP further revealed that, even upon treatment with current approved drugs such as Trikafta or at permissive temperature, the uncoupled state of ICL2 is a prominent feature of the misfolded CFTR mutants ∆F508 and N1303K that cause Cystic Fibrosis (CF). Although Trikafta treatment reduced the amount of uncoupled ICL2:NBD2 interfaces, more than 75% of F508 CFTR remained in the uncoupled state, suggesting that stabilization of this interface could produce a more efficient CF drug. CPP can characterize a protein in its native environment and measure the effect of complex PTMs and protein interactions on protein structure, making it broadly applicable and valuable for the development of new therapies.
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The Washington-Baltimore Mass Spectrometry Discussion Group is pleased to announce that our first event of 2023-2024 will be kicked off on September 11, 2023 (Monday) at Shimadzu Scientific in Columbia, MD. It is our true privilege this year that a giant in our field, Dr. John Yates III from Scripps Research, will be speaking as the keynote speaker at this event.

Our WBMSDG board has decided to include two lightning talks before the main talk starting with our October event. Each lightning talk lasts 7 minutes with no more than 5 slides, and 5 minutes for Q&A for both talks. 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

(We are updating our sponsors list for 2023-2024.)

June 2023 Meeting

Topic: Post-ASMS Poster Night and ASMS Travel Award Presentations
All attendees are invited to put up an ASMS poster

Date: Monday, June 12, 2023

Time: 6:15 pm Dinner and ASMS posters, 7:30 pm Presentations

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

Dinner: Please RSVP to Andy Qi (andy.yue.qi@gmail.com) by Friday, June 9 if you will be attending the dinner and/or if you will participate in the poster session.

ASMS Travel Award Recipients:

    • Bowen Shen, University of Maryland

: “Electrophoresis-Correlative Mass Spectrometry Enables Ultrasensitive Proteomics”

    • Ashley Frankenfield, George Washington University

: “Deep Proteome Turnover in human iPSC-derived Neurons”

    • Delaney Rutherford, National Institute on Aging

: “Mass Spectrometry Analysis with Cellular Thermal Shift Assay to Assess Senolytic Pathways in Senescent Monocytes”

Thank you to our 2022-2023 sponsors!

May Meeting

Speaker: Aleksandra Nita-Lazar, NIAID, NIH

Topic: Macrophage signaling mechanisms: deciphering protein networks

Date: Monday, May 15, 2023

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

Location: Shimadzu Scientific Instrument, Inc. Training Center 7100 Riverwood Drive, Columbia, MD 21046 (Directions)
This will be an in-person meeting. Attendees are required to show a vaccine card (either at the door or in advance using the web form) . If you have submitted your vaccine card before, your status is already recorded.

Dinner: Please RSVP to Andy Qi (andy.yue.qi@gmail.com) by Friday, May 12 if you will be attending the dinner.

Abstract: Toll-like receptor (TLR) signaling in macrophages is essential for generating effective innate immune responses. Quantitative differences dependent on the dose and timing of the stimulus critically affect cell function and often involve proteins that are not components of widely shared transduction pathways. Mathematical modeling is an important approach to better understand how these signaling networks function in time and space. We have successfully modeled the S1P signaling pathway in macrophages using selected reaction monitoring (SRM) to measure the absolute abundance of the pathway proteins. The resulting values became parameters in a computational pathway model. To model the TLR signaling networks, we developed assays for the canonical
TLR signaling pathway and related proteins and phosphoproteins and used parallel reaction monitoring (PRM) with heavy-labeled internal peptide standards to quantify protein and phosphorylated protein molecule numbers per cell in untreated and LPS-stimulated macrophages. The absolute protein abundance values were entered into a model of the TLR pathway developed using Simmune, the rule-based modeling tool with a visual interface. To reach beyond basal level quantification, the TLR signaling network model is tested further and combined with global proteomic approaches to discover
biologically important new proteins, protein complexes and PTMs involved in this innate immune pathway. The protein and PTM levels are quantified in macrophages under diverse, but well-defined conditions (different TLR ligands, whole pathogens, and cells with mutations in specific signaling molecules). These data will allow to parameterize and test the TLR network model under a variety of conditions. Together, the interconnected projects will lead to the better understanding how the immune signaling pathways are regulated and activated during an infection. This research was supported by the Intramural Research Program of NIAID, NIH.

Thank you to our 2022-2023 sponsors!

April Meeting

Joint with the Washington Chromatography Discussion Group

Speaker: Ina Nemet, Lerner Research Institute, Cleveland Clinic

Topic: Dissecting gut microbial metabolic pathways in cardiometabolic diseases by mass spectrometry-based metabolic approaches

Date: Monday, April 17, 2023

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

Location: Shimadzu Scientific Instrument, Inc. Training Center 7100 Riverwood Drive, Columbia, MD 21046 (Directions)
This will be an in-person meeting. Attendees are required to show a vaccine card (either at the door or in advance using the web form) . If you have submitted your vaccine card before, your status is already recorded.

Dinner: Please RSVP to Andy Qi (andy.yue.qi@gmail.com) by Friday, April 14 if you will be attending the dinner.

Abstract: Elucidating pathways that contribute to cardio-metabolic diseases beyond traditional risk factors, is important for developing new strategies effective in preventing and reducing disease progression. Multiple diseases including cardiovascular disease, obesity, type 2 diabetes, metabolic syndrome, and hypertension are associated with altered gut microbial structure and function. Rational design of personalized therapeutic strategies that target gut microbiota driven pathways require a comprehensive understanding of gut microbial metabolism and the relationship between systemic levels of metabolites and disease risks.
Recently we have clinically and mechanistically linked phenylacetylglutamine (PAGln), a gut microbially derived metabolite from aromatic amino acid phenylalanine, with cardiovascular disease risks. PAGln was elevated in diabetics and predicted incident risks for cardiovascular events independent of blood glucose levels. Mechanistic studies reveal PAGln acts via the adrenergic receptor. We have continued mapping out microbial metabolic pathways that are associated with adverse phenotypes in the host. The results of these studies will provide a meaningful starting point for the development of new therapeutic treatments for cardiometabolic diseases aimed at shifting nutrient fermentation away from metabolites associated with disease toward ones that are beneficial to the host.

Thank you to our 2022-2023 sponsors!