Fibrocontractile disease affects nearly 80 million people worldwide annually; yet, current treatment modalities are relatively ineffective. There is an unmet need for a novel small molecule drug to prevent fibrocontractile disease but first the mechanisms of disease formation need to be verified. Fibroblast and myofibroblast contractility is putatively responsible for fibrocontractile disease progression. Non muscle myosin II is hypothesized to be the final common effector protein in fibroblasts and myofibroblasts that promotes contractility. It is hypothesized that blockade of non muscle myosin II will prevent fibrocontractile disease progression. Non muscle myosin II isoform expression will be investigated in human ibrocontractile diseased tissue, and in contracting animal wounds. The effects of non muscle myosin II inhibition on fibrocontractile disease progression in animal models will be studied. Gain of function, loss of function and return of function approaches will be used to demonstrate the functional significance of this protein in in vitro contractility assays. The candidate is a board certified general surgeon, who has completed three years of basic wound healing research, and is expected to finish three years of Plastic Surgery training at Duke University Medical Center in July, 2008. In July 2008, he will work as an Assistant Professor in Plastic Surgery at Duke University Medical Center, with an appointment in Pathology. His short-term career development goals are to establish a career as a surgeon scientist, broaden his basic science knowledge base, improve his laboratory skills and verify that non muscle myosin II is essential for fibrocontractile disease progression. The candidate's long term goals are to translate this basic science research into clinical application by developing a novel pharmaceutical to prevent fibrocontractile disease. The candidate's primary mentor is Salvatore V. Pizzo, MD, PhD, Chairman of Pathology, and previous director of the Medical Scientist Training Program at DUMC, and his two co-meritors are L. Scott Levin, MD, Chief of Plastic Surgery at DUMC, and Daniel P Kiehart, PhD, Chairman of the Department of Biology at Duke University who investigates non muscle myosin II function and wound healing in Drosophila. The candidate foresees initially working in Dr Pizzo's laboratory for 3 years, then progressing towards independence, working for 2 years in the Keenan Plastic Surgery Laboratory as a surgeon scientist, and ultimately preparing an R01 towards the end of the 5 years. ? ? ?
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