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Genomic and Proteomic Determinants of Lower Extremity Revascularization Failure

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This five-year training program is designed to take advantage of the candidate's basic research background and tailor it to a translational patient-oriented initiative. The training module focuses on developing the applicant's working knowledge of advanced genomics/proteomics and bioinformatics with functional application to human disease. It outlines two tangible goals: 1) the basic coursework necessary to satisfy a Master of Science degree in Clinical Investigation;and 2) establishment of a multidisciplinary collaborative group of clinicians, scientists, and statisticians to create a formal functional genomics/proteomics outcomes program in Vascular Surgery at the University of Florida. The candidate's mentor is uniquely qualified to mold the career of a young academic surgeon, and the advisory panel is comprised of experts in inflammation biology, vascular biology, molecular genetics, bioinformatics, clinical trial design, and epidemiology. The didactic instruction follows the detailed curriculum of the Advanced Postgraduate Program in Clinical Investigation K30 program at the University. It outlines coursework in advanced genomics and proteomics, statistics/bioinformatics, epidemiology, clinical investigation, and ethical and responsible human subject research. Practical training in genomic/proteomic techniques and study design as well as the application of bioinformatics tools to the resultant dataset will come through direct interaction of the candidate and his mentor/ advisors. Taken together, these aspects of the development plan promise to help the candidate realize his goal of becoming an independent clinician-investigator. The proposed human research initiative takes advantage of several strengths at the University of Florida--the most important of which is the Laboratory of Inflammation Biology and Surgical Science with recognized expertise in the application of functional genomics and proteomics to human disease. Using these resources, the candidate aims to test the hypothesis that the systemic inflammatory response following vascular intervention influences the local milieu responsible for vascular repair and adaptation. The expectation being that this response is not uniform in all patients, but rather, is modulated by either some preoperative genetic predisposition or differential regulation of monocyte function that drives the vascular response towards an occlusive maladaptive phenotype. Early intervention failure with recurrent lower extremity ischemia and a negative impact on quality of life is the result. Peripheral arterial occlusive disease is a significant national health care concern and the information gained through this work will lead to new strategies to improve existing approaches to lower extremity angioplasty/stenting. It will also provide new knowledge in the overall management of cardiovascular disease on a significantly broader scope.
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