Thomas Quertermous, MD, Professor, Department of Medicine, Stanford University

Research Description: The fundamental goal of the Quertermous laboratory is to characterize the epigenetic and transcriptional mechanisms by which human trait and disease-associated allelic variation modulate causal gene expression and function. Toward that goal, we have primarily focused on coronary artery disease (CAD), the worldwide leading cause of morbidity and mortality, because of the current lack of understanding regarding the molecular mechanisms that mediate the primary disease process and the rich genome-wide association data that has been acquired over the past two decades. Studies are focused on the cellular and molecular mechanisms by which GWAS-associated genes mediate disease risk. Causal variants and genes are identified with combined human coronary artery smooth muscle cell high-order genomic datasets and complementary genome editing. Mechanistic studies employ a combination of lineage tracing, conditional gene targeting, and single-cell genomics in mouse models. As for almost all complex human diseases, CAD is mediated by transcriptional variation, and we are using single cell epigenomic approaches to map disease-relevant enhancers and study epigenetic effects that mediate disease-causal transcriptional imbalance in vascular cells. The ultimate goal of our research is to establish causal transcription factor networks that regulate pathology and disease risk, linking disease genes and lesion anatomy. We collaborate extensively with many members of the NORC.