Detailed Biography:

Research Interests: Lipoprotein metabolism; macrophage biology; and atherosclerosis. The pathogenesis of atherosclerosis is characterized by inflammatory responses of vascular cells and by the massive accumulation of lipoprotein-derived lipid in the arterial wall. Our investigations focus upon trafficking of low density lipoprotein (LDL) in the arterial wall. LDL, the chief carrier of plasma cholesterol, plays multiple roles in atherosclerosis. It provides cellular activation stimuli in the form of bioactive products of lipid peroxidation and, upon covalent modification of the apoB protein component by lipid aldehydes, produces chronic deposition of cholesteryl ester in macrophage-derived arterial foam cells. Subpopulations of LDL which are characterized by an increased content of sialyl oligosaccharide appear particularly effective in generating these cellular responses. Combinations of experimental approaches in biochemistry, cell biology, and molecular biology are utilized to address several lines of inquiry. The first is directed toward the role of lipoprotein-borne sialyl gangliosides in endothelial activation. The second is directed toward changes in hepatic biosynthesis of apoB protein-bound oligosaccharide triggered by chronic inflammation, and subsequent impact upon leukocyte extravasation. The third is directed toward endothelial expressed apoB protein as a cytokine-inducible monocyte adhesion site. These lines of investigation integrate trafficking of LDL in the arterial wall with concepts of endothelial activation and monocyte-macrophage biology to develop an understanding of early events in the pathogenesis of atherosclerosis.