Washington University in St. Louis (WU)
Despite tremendous progress in CAD/HF research, we still have an incomplete understanding of the precise cell states, transcriptional programs, and regulatory mechanism driving CAD and HF. We hypothesize that in CAD and HF, infiltrating immune cells enter the coronary artery and myocardium respectively, differentiate into diverse cell states, and interact with and cause resident stromal cells to de-differentiate into reparative and pathogenic cell states. To test this hypothesis, we are employing a reverse translation paradigm: starting with human tissue, we will leverage single cell multiomics to dissect the genomic, transcriptional, and regulatory landscape in CAD and HF to generate experimentally testable hypothesis. Next, we will test a subset of patient derived hypothesis by perturbing the immune-stromal axis in vitro and in vivo to identify potential therapeutic targets.