The Quertermous Laboratory

The fundamental goal of our laboratory is to characterize the epigenetic and transcriptional mechanisms by which human trait and disease associated allelic variation modulates 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 in our laboratory are focused on the cellular and molecular mechanisms by which GWAS-associated genes mediate disease risk. The approach is the combination of lineage tracing, conditional gene targeting, and single cell genomics. 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. Ultimate goal of our research is to establish causal transcriptional TF networks that regulate pathology and disease risk, linking disease genes and lesion anatomy.

Overall, research activities in the lab are carried out with bioinformatic and experimental approaches, with some trainees focusing on one or the other disciplines, but it is encouraged that most trainees have some expertise in both generating and analyzing the high order datasets that reflect transcriptional and epigenetic mechanisms of complex human traits.

To expand the repertoire of causal CAD genes, and the understanding of fundamental cellular and molecular processes in vascular cells, we are actively involved in two large consortia. We are assembling an arterial cell atlas for the CZI Human Cell Atlas project. Single cell data is being generated and analyzed for the eight arterial beds that mediate the bulk of human vascular disease and will be publicly available. Our lab is also participating in the Impact of Genomic Variation on Function (IGVF) consortium funded by the National Human Genome Research Institute. The IGVF Program seeks to understand how genomic variation affects genome function to influence phenotypes and our lab along with 5 other laboratories at Stanford are working together to decode role of cardiovascular GWAS variants in related disease phenotypes.