DEAN Y. LI, M.D., Ph.D.

LAB WEBSITE

B.A. University of Chicago
M.D. Washington University
PhD. Washington University

RESEARCH:

Our goal is to describe vascular development as a series of sequential and coordinated molecular events. This information is vital for understanding embryogenesis and devising strategies for the prevention and treatment of malignancies and obstructive vascular disease. We hypothesize that many genes implicated in human vascular disease play fundamental roles in vascular development.

Loss-of-function mutations in the elastin gene cause an autosomal dominant vascular disease in humans, supravalvular aortic stenosis. To understand the role of elastin in vascular development and disease, we generated mice lacking elastin. These mice die from uncontrolled vascular smooth muscle cell proliferation and migration. Thus, elastin has an unanticipated regulatory function during arterial development, controlling proliferation of smooth muscle cells and stabilizing arterial structure. Recently, we have shown that in vitro elastin regulates the migration and differentiation of vascular smooth muscle cells. Together, these data suggest that elastin may prevent vascular smooth muscle cells from dedifferentiating, proliferating and occluding vessels, pathology characteristic of all obstructive vascular diseases. We are currently testing this hypothesis in atherogenic animal models.

SELECT PUBLICATIONS:

Urness LD, Sorensen LK, Li DY (2000) Arteriovenous malformations in mice lacking activin receptor-like kinase 1. Nature Genetics 26:328-331

Li DY, Sorensen LK, Brooke B, Urness LD, Davis EC, Taylor D, Boak B, Wendel D (1999) Defective angiogenesis in mice lacking endoglin: Science 284:1534-1537

Faury G, Maher GM, Li DY, Keating MT, Mecham RP, Boyle WA (1999) Relation between outer and luminal diameter in cannulated arteries: Am. J. Physiol. Nov; 277 (Pt 2): H1745-53

Li DY, Brooke B, Davis EC, Sorensen LK, Boak BB, Eichwald E, Mecham RP, Keating MT (1998) Elastin is an essential determinant of arterial morphogenesis: Nature 393:276-280

Li DY, Faury G, Taylor DG, Davis EC, Boyle WA, Mecham RP, Stenzel P, Boak B, Keating MT (1998) Novel arterial pathology in mice and humans hemizygous for elastin: J. Clin. Invest. 102:1783-1787