Studies in HIV-1 Pathogenesis and Transmission

描述（由申请人提供）：在艾滋病毒相关的以患者为导向的研究中，这项中期职业研究者奖的主要目标是利用由此产生的受保护的时间和精力来指导布朗大学及其附属医院的新一代初级研究者。 HIV发病机制和传播的转化研究。学员将从强大的教育基础设施中招募，其中包括NIH资助的几个以艾滋病毒为中心的项目，包括培训赠款（T32 DA 013911、T32 MH 078788、T32 AA 007459），国际艾滋病培训和研究项目（D43 TW 000237，D43 TW 009597）和中心赠款，包括寿命/塔夫茨/布朗CFAR（P30 AI 042853）和布朗大学酒精研究中心艾滋病毒（P01 AA 019072）。最近资助的5年研究补助金（R 01 HD 072693）将被用作指导的即时可用基础，并将允许以患者为导向的研究，将诊所和实验室与追求以下具体目标（目标1）相连接的指令量化外源性和内源性生殖激素对绝经前后妇女生殖道HIV易感性的影响。(Aim 2）确定生殖激素是否改变负责HIV通过宫颈阴道上皮传播的机制。(Aim 3）量化生殖激素对女性生殖道中HIV依赖因素的影响。K24机制将用于支持一个新的目标，涉及对性暴力成年女性受害者的宫颈阴道进行纵向研究，目的是描述性创伤导致的炎症变化。追求这些目标将使学员能够接受有关临床研究方案的设计和管理，生物样品的收集和处理以及涉及基因和蛋白质表达和组织成像的最先进技术的实验室实验的执行的广泛指导。用于评估此K24应用程序的进展的基准将包括通过摘要，演示文稿和同行评审的出版物的数量以及职业发展赠款（NIH K系列，私人基金会）的数量来衡量的学员的生产力，这些补助金来自我的以患者为导向的研究计划。

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.