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Biomolecular Mass Spectrometry Core

$272,429P30FY2025ESNIH

University Of Pennsylvania, Philadelphia PA

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Abstract

BIOMOLECULAR MASS SPECTROMETRY CORE (BMSC): ABSTRACT The Biomolecular Mass Spectrometry Core (BMSC) is a key component of exposure assessment in the Center of Excellence in Environmental Toxicology (CEET) described in the Strategic Vision. The mission of the Core is to foster the use of biomolecular mass spectrometry to measure reporters of the exposome, (e.g., proteome, lipidome, metabolome and adductome) as biomarkers of exposure, adverse response, outcome and therapeutic response for diseases of environmental etiology. It performs work in cell-culture based models, in animal models and patient cohort studies designed in the Translational Research Support Core (TRSC). The BMSC recognizes the need to relate phenotypic changes in biomarkers with either changes in the transcriptome or with genetic variants and this is achieved by data integration performed by the Environmental Health Informatics Core (EHIC). The integration of genomic data and reporters of exposomic biomarkers offers the promise to deliver multi-omics approaches to diagnosis and prognosis. The BMSC is equipped with state-of-the-art ultraperformance liquid chromatography (UPLC)-MS and UPLC-high resolution (HR) MS instrumentation. It is also equipped with an ionchromatography system coupled to inductively coupled plasma (ICP)-MS for heavy metal analysis with speciation. In the Core untargeted approaches are followed by targeted LC-MS assays. Our targeted LC-MS assays use stable-isotope dilution (SID) LC-MS as the gold standard for precision and accuracy; many of the assays cannot be performed elsewhere in the world. The BMSC will achieve the CEET mission under the following aims: Aim 1: We will support the CEET thematic areas (Air Pollution & Lung Health; Environmental Exposures & Cancer; Windows-of- Susceptibility; and Environmental Neuroscience) and the cross-cutting theme of the effects of extreme weather on health with high-throughput services and facilitate biomarker discovery using Exposomics approaches (proteomics, lipidomics, metabolomics and adductomics). We will also support large multi-investigator grant applications, transcending CEET thematic areas. Aim 2: We will provide CEET investigators with highly sensitive and specific assays to quantify biomarkers of exposure and effect in model systems and in biofluids from population cohorts and patients. Aim 3: We will develop new assays for the thematic areas and prioritize services based on the needs of CEET investigators. Aim 4: We will provide analytical support for pilot project recipients, for preliminary studies in environmental health sciences and provide support for adjunct faculty with NIEHS funding from other universities in our area and from other Environmental Health Sciences Core Centers (EHS CCs) that do not have access to our assays. Aim 5: We will provide access and training to use state-of-the-art analytical equipment and software, for CEET investigators and their trainees, through monthly training sessions and annual workshops.

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