Scientific Human Biomarker Exposure Monitoring Core (HEMC) for the Air pollution disrupts Inflammasome Regulation in HEart And Lung Total Health (AIRHEALTH) Study

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ABSTRACT: HUMAN BIOMARKER EXPOSURE MONITORING CORE (HEMC) The Scientific Human Biomarker Exposure Monitoring Core (HEMC) is a state-of-the-art Core Laboratory at Stanford School of Medicine that builds on the extensive experience of the Stanford Human Immune Monitoring Core Laboratory (HIMC). The HEMC will serve the aims of Projects 1, 2 and 3 by performing comprehensive, standardized immune-based cell culture assays, and cardiovascular assays. The overarching goals of the HEMC are to manage and process biomarker samples, define the multidimension biomarker profile of pollutant exposure, and to provide state of the art assays for epigenic modifications relevant to pollutant exposure. The results of the experiments performed by the HEMC will be central to the individual projects of this PPG by providing needed samples to the individual projects and guiding the use of the most informative samples for mechanistic and modeling studies. To this end, our three specific aims are: Aim 1. To centrally bank air pollution cohort plasma, peripheral blood mononuclear cells (PBMCs), RNA, and DNA, and to provide those specimens to the PPG Projects for both standardized and customized assays; Aim 2. To provide standardized targeted proteomics and gene expression assays instrumental for characterizing pollution exposure signature (PES) that will be complimentary to the specific projects of the PPG; and Aim 3. To provide a standardized, innovative epigenetic assay to enhance mechanistic findings in all projects. The HEMC brings together an unparalleled set of Stanford technologies for inflammasome monitoring and mechanistic work. We have given careful and systematic thought to the selection of assays to be performed that will evaluate different aspects of pollutant exposure. Many of technologies used in the HEMC have been largely developed and optimized at Stanford and validated by institutions outside Stanford, increasing our confidence for their application to the PPG projects. In collaboration with the DMAC, the HEMC will offer innovative tools and support for this proposed PPG to enable analysis of molecular mechanisms and to find therapeutic targets for the prevention and treatment of pollution- related cardiopulmonary risks, as proposed in Projects 1, 2, and 3.