The overall goal of this training program is to identify talented, young biomedical scientists, to nurture their research interests and talents, and to equip them with mental and manual skills that will enable them to become highly productive biomedical scientists capable of developing new, creative, and effective approaches for the diagnosis, prevention, and treatment of atherosclerosis and vascular diseases. To achieve this goal, a multidisciplinary program has been developed to train predoctoral students and postdoctoral fellows in four broad areas: 1) A structural biology component will focus on elucidating the structure of biomolecules involved in lipid transport and metabolism by modern methods including electron crystallography, x-ray crystallography, and multi-dimensional NMR. 2) A biochemistry component will emphasize mechanisms of lipoprotein oxidation, lipoprotein metabolism, and interaction of platelet proteins. Applicable techniques include protein sequencing, stable isotope turnover methodology, and plasmon resonance spectroscopy. 3) A cell biology/ molecular biology component will involve studies of leukocyte adhesion, adipocyte lipid biosynthesis, cardiocyte alterations by cytokines, and platelet binding to endothelium. These studies will utilize gene knockout and transfer in mice established as models for lipid disorders, diabetes, and obesity. This component will also provide direction in understanding the basis of SMC proliferation and how specific genes are induced by blood flow and shear stress. 4) A new clinical translational component will include i) implementation of new algorithms for localization and quantification of atherosclerotic lesions by MRI, and their use for monitoring the efficacy of lipid altering interventions;ii) clinical testing of soluble TNF receptor antagonists shown to reverse undesirable effects of TNF in myocytes and animals;iii) human testing of novel gene therapy strategies shown to reverse dyslipidemia and normalize diabetes mellitus in mice. This interdisciplinary, multi-faceted training plan includes both established investigators with extensive training experience, and carefully selected junior faculty who represent a vital source of newly emerging technology and an important link in program continuity.
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