Our work focuses on atherosclerosis-related signal transduction and the genetic bases of atherosclerosis and vein graft failure, both in vitro and in vivo. We investigate the regulation of receptor protein tyrosine kinases by G protein-coupled receptor kinases (GRKs), and the role of GRKs and β-arrestins in atherosclerosis; the role of tumor necrosis factor and its receptors in atherosclerosis; and the role of the dual Rho-GEF kalirin in atherosclerosis. For in vivo modeling of atherosclerosis and neointimal hyperplasia, we use mouse carotid artery bypass grafting with either veins or arteries from gene-deleted or congenic wild type mice, as well as aortic atherosclerosis studies and bone marrow transplantation. To study receptor phosphorylation, signal transduction, and intracellular trafficking, we employ primary smooth muscle cells, endothelial cells, and macrophages derived from knockout mice or treated with RNA interference.
Key Words: atherosclerosis, G protein-coupled receptor kinases, arrestins, desensitization, phosphorylation, platelet-derived growth factor receptors, receptor protein tyrosine kinases, smooth muscle cells, neointimal hyperplasia, Rho-GEF.
Education and Training
- Fellow in Cardiology, Medicine, Duke University, 1990 - 1993
- Visiting Scientist, Massachusetts Institute of Technology, 1989 - 1990
- Research Fellow in Medicine, Medicine, Brigham and Women's Hospital, 1988 - 1989
- Medical Resident, Medicine, Beth Israel Deaconess Medical Center, 1985 - 1988
- M.D., Harvard University, 1985
- Mechanistic studies of Mas receptor activation and its role in aortic aneurysm formation
- Multidisciplinary Heart and Vascular Diseases
- Role of Drebrin in Atherosclerosis
- Anti-atherogenic Mechanisms of the Dual Rho-GEF Kalirin
- Regulation of B-arrestin2's pro-atherogenic activity by the deubiquitinase USP20
- Role of Drebrin in Vascular Smooth Muscle Remodeling