Professor of Laboratory Medicine and Pathobiology
My research is focused on understanding the molecular mechanisms involved in the disease atherosclerosis. We are particularly interested in the initiation of atherosclerosis, and the atherosclerotic complications of plaque rupture and calcification. We are investigating mechanisms of vessel wall thickening, and remodeling using experimental models of arterial injury and atherosclerosis in mouse and rat, studying the role of extracellular matrix, cell-surface integrin receptors, the novel discoidin-domain receptors (DDRs) and matrix metalloproteinases (MMPs) and cadherins in mediating SMC and macrophage responses. To achieve these aims we are using laser capture microdissection, quantitative real-time PCR, and immunohistochemistry to study the expression of matrix, receptors and MMPs in diseased/injured vessels. We are currently using several lines of transgenic mice which overexpress or have gene deletions for components of the extracellular matrix, DDR and MMP families. These in vivo experiments are paralleled by a series of in vitro studies designed to determine the matrix components or matrix degradation products that directly stimulate MMP production and SMC migration after injury, and signaling pathways downstream of DDR1 receptors in SMCs and macrophages. In addition, we are working on developing nanotechnology and microfluidic systems to perform high-throughput assays to develop drugs to antagonize these molecular players.