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overview I am an enthusiastic researcher with specific training and expertise in atherosclerosis pathology, lipid metabolism and molecular biology. Since being appointed as a faculty member in Meharry Medical College 12 years ago, I have been successful in acquiring research funding from the National Institutes of Health and the American Federation for Aging Research (AFAR). Our laboratory has developed a number of techniques in studying the pathogenesis of atherosclerosis in vitro and in vivo. Specifically: a) we have developed methods to assess the histology and immunohistochemistry changes in mouse tissues; b) refined molecular tools for quantifying the steady-state levels of proteins in these target cells and tissues; c) refined methods for assessing not only the steady state levels of mRNAs but also the efficiency mRNA transcription and translation in tissues and cells; and d) developed a proteomics laboratory, which is equipped with 2-D electrophoresis systems, protein spot picker, Typhoon laser scanner and MALDI-TOF-mass spectrometry. With this system, we examined the changes induced by apoE-deficient lipoproteins, atherosclerosis and hypertension in protein profile in cultured cells, animal tissues and human blood. To test many hypotheses at the cellular level, our laboratory has developed protocols for the successful culturing of mouse endothelial cells, smooth muscle cells and peritoneal macrophages that overexpress or underexpress various genes. To study the impact of various interventions on atherosclerosis in vivo, we developed mouse models by crossbreeding existing transgenic and knockout mice. An example is the mouse model that lacks apoE and overexpresses antioxidant enzyme GPx4. Therefore we expect the studies in this proposal to proceed without any technical difficulties. More than this, I have established working relationships with several faculties at Vanderbilt (which is ~ 2 miles from Meharry). As background, in spring, 1999, Meharry and Vanderbilt co-signed an MOU forming the Meharry-Vanderbilt Alliance. Since that time, we have worked together in areas of mutual interest including research, patient care and education. As part of this agreement, our libraries and research cores are open for use by faculty, students on both campuses and a number of faculty hold adjunct appts at the other institution. Thus since ~2005, I have enjoyed a cordial working relationship with faculty at Vanderbilt U Medical Ctr such as L.Jackson Roberts, MD (discoverer of isoprostanes who studies free-radical damage/oxidative stress) and Sergio Fazio, MD, PhD and MacRae Linton, MD, experts in dyslipidemia and atherosclerosis. Although Dr. Fazio recently moved to the West Coast, I frequently contact Drs. Roberts and Linton advice. I also collaborated with several cardiovascular research and other experts, including Drs. Shawn Goodwin and ZhongMao Guo at Meharry and Arlan Richardson at UT-San Antonio. Finally, the research core facilities at Meharry are superb in supporting our proposed research, including the molecular biology core, the confocal morphology core, and the tissue preparation for histology/ immunohistochemistry core. Thus, all of the essential equipment and expertise needed for our proposed work is readily available in this research environment.
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