The main focus of my laboratory is on development and differentiation of coronary vessels. Progenitors for the coronary vasculature are found in the proepicardium, a transient cell population that arises independently of the heart itself, and provides epicardial cells to the looped heart tube during cardiac development. The appearance of the epicardium and its derivatives in evolution correlates with the transition of the heart from a primitive tubular structure with a thin-walled, epithelial-type myocardium, as is found in pre- and early chordates, to a thick multilayered pumping organ found in most vertebrates.

Fate mapping studies show that proepicardial cells are the forerunners for the endothelium, smooth muscle and adventitial cells of the coronary vasculature. Formation of the coronary vessels occurs by an epithelial to mesenchymal transformation (EMT) of proepicardial cells, followed by vasculogenesis in the subepicardial layer, assembly and remodeling of a primitive coronary plexus, and investment by coronary smooth muscle cells (CoSMCs).

My laboratory uses molecular biological and developmental genetic approaches to identify mechanisms for CoSMC commitment and differentiation during heart development. We use both chick embryo and mouse models to explore the relation between EMT and CoSMC differentiation. We are currently using transgenic and knockout approaches to examine the role of hedgehog signaling, rhoGTPase activation, and cytoskeletal remodeling in the stimulation of SRF and Tbx-dependent transcription that mediates SMC differentiation in the coronary lineage.