Daniel Greif, MD

Our laboratory investigates blood vessel development and disease as well as fibroblasts in lung development and fibrotic disease. To this end, we utilize fundamental biochemical, genetic/epigenetic, -omic, computational and developmental biological approaches. We uncovered novel smooth muscle cell progenitors that undergo clonal expansion during diverse vascular diseases, such as pulmonary hypertension and atherosclerosis.

Our ongoing and planned studies of vessel and lung development, maintenance and disease use similar fundamental approaches. Our initial investigations focused on pulmonary artery development, and 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. Little is known about the maintenance of blood vessels, and we are interested in evaluating 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 and pericytes, such as atherosclerosis, supravalvular aortic stenosis, restenosis, intracranial hemorrhage and pulmonary hypertension. In addition, we have extended our studies to lung fibrosis which is an important cause of hypoxia and hence pulmonary hypertension. Furthermore, we are studying clinical samples obtained from patients with vascular and lung diseases and relating them to our findings in animal models and cultured cells.

Current Research Projects:

• Excess smooth muscle in pulmonary hypertension: pathogenesis and reverse remodeling
• Arterial development, disease (atherosclerosis, supravalvular aortic stenosis), aging: progenitor cell specification, migration and epigenetics.
• Pericytes and blood-brain barrier formation: implications for intracerebral hemorrhage.
• Fibroblasts in lung development and fibrotic disease