HIV, HCV, and gender effects on Liver, Bone, and Vascular Health

描述（申请人提供）：我是一名传染病和HIV流行病学方面的内科医生，主要研究方向是HIV和HCV感染。自2000年加入加州大学旧金山分校（UCSF）以来，我开发了一个全国公认的临床转化研究项目，专注于了解HIV感染和HCV感染与脂肪组织改变、代谢和炎症性紊乱（包括肝脂肪变性）之间的关系。我目前支持的研究包括：1)一个R01，建立了一个主要由300名HIV和HCV单感染、HIV/HCV合并感染和未感染的男性组成的队列，以确定内脏肥胖、HIV、HCV及其代谢的影响

DESCRIPTION (provided by applicant): I am an internist trained in infectious disease and HIV epidemiology, whose research is focused on HIV and HCV infections. Since joining the faculty at the University of California, San Francisco (UCSF) in 2000, I have developed a nationally recognized clinical translational research program focused on understanding the associations of HIV infection and HCV infection with adipose tissue changes, and metabolic and inflammatory perturbations, including hepatic steatosis (or fatty liver disease). My currently supported research includes: 1) an R01 that establishes a cohort of mainly 300 men with HIV and HCV monoinfection, HIV/HCV coinfection and those with neither infection to determine the effects of visceral adiposity, HIV, HCV and their metabolic and inflammatory consequences on fatty liver disease (VAHH Study); and 2) a U01 in a large prospective cohort of women with and at risk for HIV (Women's Interagency HIV Study [WIHS]) that has a core goal to determine the contribution of HIV, host immune mechanisms, behavioral and cardiovascular risk factors to organ injury. Data from the Study of Fat Redistribution and Metabolic Change in HIV infection (FRAM) also is available to me. Within this framework, I propose to expand my research agenda to: (1) investigate the contribution of HIV, HCV, and their metabolic and inflammatory consequences to long term outcomes including liver disease progression measured using novel non-invasive techniques, as well as osteoporosis and vascular disease; (2) determine sex differences in the association of HIV, HCV, and their metabolic and inflammatory consequences with long term outcomes (by pooling the detailed outcomes data collected from WIHS women and VAHH and FRAM men and women) and how the menopausal transition may further alter these relationships in women compared to men; and (3) use the results to define sex-specific mechanisms that will enable interventional studies that take into account sex effects in the pathogenesis of these outcomes in HIV-infected and HCV-infected persons. With access to the broad range of rigorously collected measurements from these three cohorts (including measurement of liver fibrosis by ultrasound based transient elastography, hepatic steatosis and visceral adipose tissue by MRI, bone mineral density by Dual Energy X-Ray Absorptiometry scans, and carotid intima media thickness by ultrasound), I propose to expand my mentoring program to mentees with an interest in HIV and HCV infections from a multitude of disciplines including infectious diseases, hepatology, endocrinology and metabolism, cardiology, and radiology. The ability to bring in mentees from disciplines outside of infectious diseases will further enrich my research program. I plan to also seek additional training in professional leadership and how to build a structured and sustainable mentoring program in order to develop the next generation of clinical investigators in HIV and HCV research, and to ensure that they will ultimately become skilled mentors themselves.