Studies in HIV-1 Pathogenesis and Transmission

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DESCRIPTION (provided by applicant): The major goal of this Mid-Career Investigator Award in HIV related Patient-Oriented Research is to use the resulting protected time and effort to mentor a new generation of junior investigators at Brown University and its affiliated hospitals in translational studies of HIV pathogenesis and transmission. Mentees will be recruited from a robust educational infrastructure that includes several NIH funded HIV-centric programs including training grants (T32DA013911, T32MH078788, T32AA007459), international AIDS training and research programs (D43TW000237, D43TW009597) and Center grants including the Lifespan/Tufts/Brown CFAR (P30AI042853) and the Brown University Alcohol Research Center on HIV (P01AA019072). A recently funded 5-year research grant (R01HD072693) will be used as an immediately available foundation for mentoring and will allow instruction in patient oriented research that connects the clinic and laboratory with the pursuit of the following specifi aims (Aim 1) To quantify the effect of exogenous and endogenous reproductive hormones on HIV susceptibility of the reproductive tract of pre- and post-menopausal women. (Aim 2) To determine if reproductive hormones alter mechanisms responsible for HIV transmission through cervicovaginal epithelia. (Aim 3) To quantify the effect of reproductive hormones on HIV dependency factors in the female genital tract. The K24 mechanism will be used to support a new aim involving the longitudinal study of the cervicovaginal tract of adult women victims of sexual violence with the goal of characterizing inflammatory changes that result from sexual trauma. Pursuit of these aims will allow mentees to receive broad instruction on the design and management of clinical research protocols, collection and processing of biologic samples and execution of laboratory experiments involving state-of-the-art techniques in gene and protein expression and tissue imaging. Benchmarks for evaluating the progress of this K24 application will include the productivity of mentees measured by the number of abstracts, presentations and peer-reviewed publications as well as the number of career developments grants (NIH K- series, private foundation) that result from my patient oriented research program.