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Regulation of Monocyte Endothelial Interactions My research deals with the events mediating chronic inflammatory processes such as occur in atherosclerosis, cancer and rheumatoid arhtritis. Our research employs cell, molecular and biochemical methods to address several questions related to the regulation of the specific interaction of endothelial cells with monocytes. We have shown by Mass Spectroscopy and HPLC that particular oxidized phospholipids play a major role in activating endothelial cells to increase their interaction with monocytes. We have demonstrated that these phospholipid oxidation products are increased in cells exposed to oxidative stress, viral infection and are increased in atherosclerotic lesions. Current studies are focused on identifying the novel receptors for these lipids and the transcriptional and signal transduction pathways activated by them. For these studies we are employing a number of basic molecular biology methods as well as microarrays, proteomics and RNAi. Several candidate receptors and pathways have now been identified using cell culture. To verify their role, in vivo, human disease tissue is being analyzed for activation of particular pathways. In addition, we are testing the role of candidates by over and underexpression in mice using endothelial specific promoters. These studies should allow identification of important and novel pathways mediating chronic inflammatory diseases.
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