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.

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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!