Elaine Raines, MS
Research Professor, Department of Pathology
The Raines laboratory is examining the cellular and molecular mechanisms involved in formation of lesions of atherosclerosis. Evaluation of diseased and normal human vessels helps identify genes altered during lesion formation, and primary cultures of human vascular cells are used to define the role of candidate genes in regulation of vascular cell migration, proliferation and survival. The importance of specific molecular pathways are subsequently tested in mouse models of atherosclerosis using a combination of gene therapy and gene targeting approaches. Specific pathways currently being investigated include: (1) use of a novel macrophage-specific retroviral gene expression system to test the role of macrophage-derived matrix metalloproteinases in atherosclerotic lesion progression and plaque rupture; (2) regulation of endothelial cell and monocyte adhesion molecules and ligands critical to the inflammatory response by a family of proteases (ADAMs) that can rapidly shed these molecules from the cell surface; (3) use of proteomic approaches to identify novel substrates of ADAM17 and matrix metalloproteinases identified in lesions of atherosclerosis; (4) generation of mice with floxed ADAM17 alleles to test effects of its targeted deletion from endothelial cells and macrophages; and (5) characterization of signals from the extracellular matrix that regulate the ability of smooth muscle cells to respond to stimulants of migration and growth.