Persistent Functional Immune Defects in Treated HIV Infection

项目摘要 彼得亨特，医学博士是一个医学副教授在加州大学旧金山分校实验医学部和一个 国际公认的以患者为导向的转化研究（POR）的领导者，专注于病因和 在治疗的HIV感染中免疫激活的后果。他正在提交这个K24中期职业生涯 开发应用程序，为他提供受保护的时间来指导初级调查员，为他提供 专门的指导技能培训，并继续发展他的POR计划。主持人：这个提案 将建立在亨特博士的高生产力的研究计划，由200多名同行评审的例子 出版物，引文h指数为52，以及强大的研究资金基础，包括三个R 01赠款和两个 DARE合作实验室和amfAR艾滋病毒治疗研究所的大型项目。他已经 在指导方面表现出良好的记录，特别是在多学科团队科学方面，包括4 已成功申请K23/K 01奖项的学员，以及两名已获得 独立的R系列赠款。他也是2015年UCSF艾滋病研究所奖的获得者， 指导。环境：他有丰富的基础来支持他的学员，包括获得 旧金山弗朗西斯科>2000名HIV感染者的UCSF SCOPE队列以及与其他几个 多中心队列（LSOCA，UARTO，CNICS）和研究网络，包括ACTG，他曾在那里工作 炎症和终末器官疾病委员会主席导师培训：K24奖项将 透过密集的工作坊和训练单元，进一步提升他的师友技能， UCSF CTSI导师培训计划和UCSF-GIVI导师计划。他还将 在他职业生涯的下一个阶段，他得到了一群强大的职业导师的指导。研究计划： 激发研究计划的首要假设是，亚临床免疫缺陷，尽管治疗 HIV感染降低了CD 8 + T细胞介导的CMV监视，这反过来又导致微生物易位 和心脏代谢并发症具体目标是：1）评估无症状CMV的贡献 复制到经治疗的HIV感染中的微生物易位和血管功能障碍的可溶性标志物，2） 评估经治疗的HIV感染与炎性CMV特异性CD 8 + T细胞相关的程度 脂肪组织浸润和胰岛素抵抗，以及3）评估CMV特异性 CD 8 + T细胞出现在治疗的HIV感染中。这些研究也将作为理想的POR培训平台， 他的学员们

Project Summary Peter Hunt, MD is an Associate Professor of Medicine in the UCSF Division of Experimental Medicine and an internationally recognized leader in translational Patient-Oriented Research (POR) focused on the causes and consequences of immune activation in treated HIV infection. He is submitting this K24 Mid-Career Development application to afford him protected time to mentor junior investigators, to provide him with dedicated mentorship skills training, and to continue to grow his POR program. The candidate: This proposal will build upon Dr. Hunt's highly productive research program, exemplified by over 200 peer-reviewed publications, a citation h-index of 52, and robust research funding base including three R01 grants and two large projects in the DARE collaboratory and amfAR Institute for HIV Cure Research. He has already demonstrated a strong track record for mentoring, particularly in multidisciplinary team science, including 4 mentees who have successfully applied for K23/K01 awards, and two who have gone on to secure independent R-series grants. He is also the recipient of the 2015 UCSF AIDS Research Institute Award for Mentoring. The environment: He has a rich foundation for supporting his mentees including access to the UCSF SCOPE cohort of >2000 HIV-infected individuals in San Francisco and connections to several other multicenter cohorts (LSOCA, UARTO, CNICS) and research networks including the ACTG, where he served as Chair of the Inflammation and End Organ Disease Committee. Mentorship training: This K24 award will further enhance his mentorship skills through intensive workshops and training modules supported by the UCSF CTSI Mentorship Training Program and the UCSF-GIVI Mentoring the Mentors program. He will also be coached by a robust group of career mentors as he navigates this next phase of his career. Research plan: The overarching hypothesis motivating the research plan is that subclinical immunodeficiency despite treated HIV infection decreases CD8+ T cell-mediated CMV surveillance, which in turn leads to microbial translocation and cardiometabolic complications. The specific aims will: 1) assess the contribution of asymptomatic CMV replication to soluble markers of microbial translocation and vascular dysfunction in treated HIV infection, 2) assess the degree to which treated HIV infection is associated with inflammatory CMV-specific CD8+ T cell infiltration of adipose tissue and insulin resistance, and 3) assess whether maturational defects in CMV-specific CD8+ T cells occur in treated HIV infection. These studies will also serve as ideal POR training platforms for his mentees.