School of Medicine

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  • Brian Wayda

    Brian Wayda

    Postdoctoral Scholar, Cardiovascular Medicine
    Fellow in Medicine

    Current Research and Scholarly InterestsHeart transplant policy and outcomes, cost-effectiveness, mathematical modeling

  • Chad S. Weldy, M.D., Ph.D.

    Chad S. Weldy, M.D., Ph.D.

    Postdoctoral Medical Fellow, Cardiovascular Medicine
    Fellow in Medicine
    Resident in Medicine

    Current Research and Scholarly InterestsAs a physician-scientist in the lab of Dr. Quertermous I work to understand the genetic basis of cardiovascular disease and the transcriptional and epigenomic mechanisms of atherosclerosis. My work is focused across three main areas of cardiovascular genetics and mechanisms of coronary artery disease and smooth muscle biology:

    1.CRISPRi screening with targeted perturb seq (TAPseq) to identify novel CAD genes in human coronary artery smooth muscle cells
    2.Investigation of the epigenetic and molecular basis of coronary artery disease and smooth muscle cell transition in mice with conditional smooth muscle genetic deletion of CAD genes Pdgfd and Sox9
    3.Defining on single cell resolution the cellular and epigenomic features of human vascular disease across vascular beds of differing embryonic origin

    My work with Dr. Quertermous is focused on driving discovery in vascular biology by understanding how common genetic variation in humans in complex disease can lead to novel understandings of disease mechanism. With nearly 100,000 GWAS loci discovered across all complex disease, and nearly 300 GWAS loci identified within coronary artery disease, the methods by which GWAS loci are mapped to causal gene is often times limited based proximity to lead SNP without confirmatory functional genomic testing. By using CRISPRi screening in human coronary artery smooth muscle cells with targeted perturb seq (TAPseq), we aim to epigenetically modify specific GWAS loci to then understand enhancer-gene pairs and identify causal CAD genes within the region of a CAD GWAS loci. For identified CAD genes with high confidence for their causality, understanding how CAD genes modify smooth muscle cell state transition within the vascular wall and the epigenomic mechanisms by which this transition occurs is crucial. By using a vascular smooth muscle cell lineage traced mouse model, we can induce smooth muscle specific deletion of CAD genes, Pdgfd and Sox9 to better understand their causal mechanism in vascular disease with single cell RNAseq and single cell ATACseq. Understanding this cell state transition and epigenomic basis of disease is further expanded to human disease with collaboration from our cardiothoracic surgical colleagues. By harvesting human vascular samples at the time of transplant or organ donation, we have the unique ability to understand on a single cell resolution the mechanisms of vascular disease. Importantly, by comparing the cellular gene expression and cell population with scRNAseq in combination with understanding chromatin accessibility on single cell resolution with scATACseq across vascular beds from differing embryonic origin (coronary, ascending aorta, aortic arch, descending thoracic, infrarenal, carotid artery) we can work to understand why there is differential susceptibility to vascular disease across vascular sites and the epigenomic and transcriptional mechanisms that facilitate this differential susceptibility.

    This work attempts to apply multiple scientific research arms to ultimately lead to novel understandings of vascular disease and discover important new therapeutic approaches for drug discovery.