Cardiovascular disease is the number one cause of death globally. In order to gain critical insights into the pathogenesis of diverse cardiovascular pathologies, my laboratory utilizes fundamental biochemical, genetic and developmental biological approaches to investigate how blood vessels initially form, are maintained and go awry in disease. Our research primarily focuses on vascular mural cells (smooth muscle cells and pericytes) and spans from cultured cells to mouse models to human samples. With cellular resolution, we compare and contrast the patterns of cell differentiation, proliferation, and migration as well as the underlying signals during morphogenesis of the pulmonary artery, aorta and cerebral vasculature. In addition, little is known about the maintenance of blood vessels, and we aim to evaluate the patterns of cell turnover, proliferation and migration as well as principal molecular mechanisms in the adult vessel wall. Moreover, diseases of the vasculature are thought to largely involve a recapitulation of developmental programs, and we study animal models of vascular diseases that involve ectopic and aberrant mural cells, such as atherosclerosis, supravalvular aortic stenosis, intracranial hemorrhage and pulmonary hypertension. The excess and ectopic accumulation of smooth muscle cells and smooth muscle-derived cells is a critical pathological feature of lesions of diverse vascular diseases, but underlying mechanisms are poorly defined. Seminal work from our lab indicates that novel smooth muscle cell progenitors play a vital role in this process. We have recently extended our investigations to myofibroblasts and lung fibrosis which is an important cause of hypoxia and hence, pulmonary hypertension. Finally, we study clinical samples obtained from patients with vascular and lung diseases and relate them to our findings in animal models and cultured cells. Taken together, our studies promise to continue to yield novel insights into disease pathogenesis that will advance therapies for human pathologies.
Daniel M. Greif, MD