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!

March Meeting

Speaker: Robert Cole, Johns Hopkins University School of Medicine

Topic: What’s on your albumin?

Date: Monday, March 20, 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, March 17 if you will be attending the dinner.

Abstract: Environmental exposures contribute to chronic disease risk substantially more than heritable genetic variants. Outdoor air pollution is a complex environmental
mixture which is responsible for over 4 million deaths each year, an impact that is projected to rise over the next several decades. The International Agency for Research on Cancer (IARC) has declared outdoor air pollution to be Group 1 human carcinogen. Outdoor air is a complex mixture of volatile organic toxins and carcinogens (e.g., aldehydes and benzene), sulfur dioxide, nitrogen oxides, polycyclic aromatic hydrocarbons, and particulate matter. Assessing personal exposure to environmental toxicants in complex mixtures, such as outdoor air pollution, is a critical challenge for predicting disease risk. Thus, developing and validating biomarkers which reveal exposure to these complex mixtures would advance individual risk analysis. Using human serum albumin (HSA)-based biomonitoring, we reported dosimetric relationships between adducts at HSA Cys34 and ambient air pollutant levels. However, modifications at other sites in HSA may reveal a great number of novel adducts and provide a panel of exposure biomarkers for disease risk. To bridge this gap, we developed a novel untargeted mass spectrometry-based method, termed Pan-Protein Adductomics (PPA),
to agnostically detect and quantify modifications at multiple residues in human serum albumin (HSA). Our PPA method combines nanoflow-liquid chromatography, gas-phase fractionation, overlapping-window data-independent acquisition, and high-resolution tandem mass spectrometry to assay modifications on HSA. Our initial application of PPA is to assess temporal changes in HSA modifications in non-smoking women exposed to high levels of outdoor air pollution. While we are currently focused on modifications in albumin, the PPA approach is applicable to any protein and may expand the knowledge base of protein modifications.

Thank you to our 2022-2023 sponsors!

February Meeting

Speaker: Zachary Goecker, NIST

Topic: Developing Reproducible Methods in Site-Specific Glycosylation Analysis

Date: Monday, February 27, 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, February 24 if you will be attending the dinner.

Abstract: Many proteins are glycosylated at multiple sites, and each site can contain complex
distributions of attached glycans. Until recently, reliable determinations of these distributions have not been possible. Instead, glycosylation analysis of glycoproteins has been primarily accomplished by releasing and identifying glycans, thereby losing all protein site-specific information. This glycomics approach works well for understanding the diversity of glycosylation in a digest, but does not answer questions relevant to site-specific structures (glycan microheterogeneity) and therefore is not as useful in determining direct functional implications. Recent developments in high resolution mass spectrometry have opened the door for the identification of intact glycopeptides. This study assesses methods in site-specific analysis of intact glycopeptides to demonstrate
reproducibility and measure variation in glycosylation quantitatively between different experimental factors. Here, we report the use of stepped HCD fragmentation, contingent ion scan, and many downstream data filters for the production of highly robust and reproducible glycosylation distribution spectra. In this presentation, we will report site-specific glycosylation profiles on glycoproteins from Sars-Cov-2, influenza, blood serum, and breastmilk. Results demonstrate that glycosylation profiles are highly reproducible among replicates and different digestion methods. However, glycosylation patterns do change based on factors such as source, proteins sequence, and glycosylation site.

Thank you to our 2022-2023 sponsors!

January Meeting

Speaker: Jace Jones, University of Maryland School of Pharmacy

Topic: The Pursuit of How Structure Impacts Function: From Lipids to Oligonucleotides

Date: Monday, January 23, 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, January 20 if you will be attending the dinner.

Abstract: The functional role of a biological molecule hinges on its unique structure. The context by which structure impacts function is a vital piece of information that can
provide insight into underlying biological processes. One set of biological molecules that have received renewed interest for their biological significance and potential role as markers of cellular dysfunction are lipids. Cellular lipids have significant potential to inform on physiology owing to the pivotal role lipids play in many biological processes including cellular integrity, energy storage, and signaling pathways. In this presentation, I will share several examples of our multidimensional approach using separations (liquid and gas-phase), adduct consolidation, and mass spectrometry to characterize lipid structure. I will also present our recent progress on the lab’s effort to translate our analytical methods to the analysis of oligonucleotide therapeutics.

Thank you to our 2022-2023 sponsors!

December Meeting

Speaker: Stephen Valentine, West Virginia University

Topic: Developing Next-Generation Tools for Native Mass Spectrometry

Date: Monday, December 12, 2022

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, December 9 if you will be attending the dinner.

Abstract: Native mass spectrometry (MS) is a powerful approach for structuralelucidation of large biomolecules. A number of technical and instrumental advances have enabled studies of diverse species ranging from protein machines to whole virus particles. However, biomolecules such as partially structured/unstructured proteins present a particular challenge to native MS. This presentation describes the development of new ionization technology with advantages in sensitivity and functionality for the study of these challenging molecules. The methods offer the best opportunity to study biomolecule conformer formation with broad implications for the study of disease processes and the development of therapeutics.

Thank you to our 2022-2023 sponsors!