We initially investigated the origins of the smooth muscle and adventitial cells of the pulmonary artery and delineated with cellular resolution the patterns of cell differentiation, proliferation, recruitment and migration in the developing pulmonary arterial wall. Furthermore, we have initiated a genetic dissection of the molecular processes and signals that underlie blood vessel formation and have demonstrated a key role of the platelet derived growth factor pathway in this process.
Our ongoing and planned studies of vessel development, maintenance and disease use similar fundamental approaches. For instance, we are studying the morphogenesis of the walls of other vessels, such as the aorta and cerebral vasculature, and comparing and contrasting their morphogenesis with that of the pulmonary artery. In addition, little is known about the maintenance of blood vessels, and we are embarking on a study to evaluate the patterns of cell turnover, proliferation and migration as well as the underlying mechanisms in the adult vessel wall. Moreover, diseases of the vasculature are thought to largely involve a recapitulation of developmental programs, and we are applying our approaches to study animal models of vascular diseases that involve ectopic and aberrant smooth muscle cells, such as pulmonary artery hypertension, atherosclerosis, supravalvular aortic stenosis, restenosis, and aneurysmal diseases. Finally, we will study clinical samples obtained from patients with vascular diseases and relate them to our findings in animal models.
Current Research Projects:
- Excess smooth muscle in pulmonary hypertension: cellular origins and recruitment and the role of pluripotency factors.
- Aortic wall development and disease: specification, migration and differentiation.
- Mural cell TGFβ signaling and blood brain barrier formation: implication for intracerebral hemorrhage.