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Persistent Functional Immune Defects in Treated HIV Infection

HIV感染治疗后持续存在功能性免疫缺陷

基本信息

批准号：
10593968
负责人：
PETER W HUNT
金额：
$ 18.43万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-07 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10593968
关键词：
AIDS clinical trial group Acquired Immunodeficiency Syndrome Address Adipose tissue Aging Anti-Inflammatory Agents Automobile Driving Award Blood Vessels CD4 Positive T Lymphocytes CD8-Positive T-Lymphocytes California Cardiovascular system Cells Cessation of life Clinical Cytomegalovirus Data Dedications Defect Diabetes Mellitus Disease Educational workshop Environment Epithelial Cells Etiology Event Exhibits Foundations Frequencies Funding Grant HIV HIV Infections HIV Seropositivity Heart Diseases Immune Immunologic Deficiency Syndromes Immunologics Impairment Individual Inflammation Inflammatory Insulin Resistance International Intervention K-Series Research Career Programs Laboratories Life Expectancy Link Malignant neoplasm of lung Mediating Medicine Mentored Research Scientist Development Award Mentors Mentorship Mid-Career Clinical Scientist Award (K24)Modernization Morbidity - disease rate Non-Insulin-Dependent Diabetes Mellitus Organ Pathway interactions Peer Review Peptides Persons Phase Physicians Placebos Population Process Productivity Publications Randomized, Controlled Trials Recovery Reporting Research Research Institute Research Personnel Research Training Risk Role San Francisco Science Scientist Secure Series Smoking Substance Use Disorder T cell infiltration T-Cell Activation T-Lymphocyte TNF gene Time Training Training Activity Training Programs Universities Valganciclovir Vascular Diseases Vascular Endothelium Viral antiretroviral therapy base cardiometabolism career career development co-infection cohort collaboratory disorder risk gastrointestinal epithelium high risk immune activation improved indexing inflammatory marker inhibitor interest lifestyle factors microbial mid-career faculty mortality multidisciplinary patient oriented research programs skills skills training systemic inflammatory response

项目摘要

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.

项目总结