Research

Cardiovascular and pulmonary diseases are major causes of death globally. My laboratory utilizes multi-disciplinary approaches to investigate how blood vessels initially form, are maintained and go awry in disease. In addition, we study lung development and fibrosis. Our research spans from cultured cells to mouse models to human samples. We aim to gain critical insights into the pathogenesis of diverse cardiovascular and pulmonary pathologies and leverage these insights into novel therapeutics and diagnostics for human disease.

Our laboratory investigates blood vessel development and disease as well as fibroblasts in lung development and fibrotic disease. To this end, we utilize cutting-edge biochemical, developmental biological, genetic/epigenetic, -omic and computational 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, aging and disease use similar fundamental approaches. Our investigations have evaluated morphogenesis of the pulmonary artery, aorta and cerebral vasculature. Little is known about the maintenance of blood vessels during adulthood, 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. Aging is a major risk factor for chronic disease, and we are studying the aging of the vascular system. Finally, we are investigating animal models of diseases that involve ectopic and aberrant vascular mural cells (i.e., smooth muscle cells and pericytes), such as atherosclerosis, supravalvular aortic stenosis, restenosis, metabolic syndrome, 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.

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