Studies in HIV-1 Pathogenesis and Transmission

描述(由申请者提供)：这个艾滋病毒相关患者导向研究的职业中期调查员奖的主要目标是利用由此产生的受保护的时间和努力来指导布朗大学及其附属医院的新一代初级调查人员 艾滋病毒致病机制和传播的翻译研究。学员将从强大的教育基础设施中招募，其中包括由NIH资助的几个以艾滋病毒为中心的项目，包括培训补助金(T32DA013911、T32MH078788、T32AA007459)、国际艾滋病培训和研究项目(D43TW000237、D43TW009597)和中心赠款，包括LIFESPAN/Tuft/Brown CFAR(P30AI042853)和布朗大学酒精研究中心(P01AA019072)。最近资助的为期5年的研究补助金(R01HD072693)将被用作立即可用的指导基础，并将允许指导以病人为导向的研究，将临床和实验室与追求以下具体目标(目标1)联系起来，以量化外源性和内源性生殖激素对绝经前和绝经后妇女生殖道艾滋病毒易感性的影响。(目的2)确定生殖激素是否改变了通过宫颈阴道上皮传播艾滋病毒的机制。(目的3)量化生殖激素对女性生殖道中艾滋病毒依赖因素的影响。K24机制将用于支持一项新的目标，该目标涉及对性暴力的成年女性受害者的宫颈阴道部进行纵向研究，目的是特征性创伤引起的炎症性变化。对这些目标的追求将使学员能够在临床研究方案的设计和管理、生物样本的收集和处理以及实验室实验的执行方面获得广泛的指导，这些实验涉及基因和蛋白质表达以及组织成像方面的最先进技术。评估K24申请进展的基准将包括通过摘要、演示文稿和同行评议出版物的数量以及我的以患者为导向的研究计划产生的职业发展拨款(NIH K系列，私人基金会)的数量来衡量受训者的生产力。

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.