The overarching goal of the Emory SCORE is to advance the quality of women's health research by leveraging the rich, collaborative and interdisciplinary research environment at Emory University to grow NIH and other extramurally funded research in women's health. The long-term vision is to develop a program at Emory that serves as a regional hub for studying the influence of biological sex on the outcomes of infectious diseases and for promoting the normalization of sex as a biological variable in research with the goal of improving women's health. These goals will be met through a) the implementation of 3 cross-cutting Research Projects employing the ?HIV-host pathogen interaction? as a model for probing the influence of sex on the pathology and pathogenesis of infectious diseases; b) the development of a Leadership Administrative Core (LAC); c) the establishment of a Career Enhancement Core (CEC) to foster the career of junior investigators working in women's health research; and d) a Biostatistics Resource Core (BRC) to optimize the rigor of all SCORE- supported research. Our focus on infectious diseases highlights the global burden of these conditions in women, aligns with the priorities of the NIH Office of Women's Health Research (OWHR), and capitalizes on Emory's research strengths in HIV translational research, basic immunology, and anti-viral drug development. The three Research Projects will explore the synergy between HIV induced immune activation and chronic inflammation and that induced by estrogen insensitivity observed in women aging with HIV infection. In the Neuro hypothalamic pituitary adrenal (HPA) axis Project 1 (Drs. Neigh & Michopoulos), we speculate that HIV interacts with multiple factors including stress exposure to decrease systemic estrogen levels and down regulate cellular expressions of estrogen receptors thereby creating relative estrogen insufficiency state with consequent heightening of chronic inflammation in women living with HIV (WLH). Using basic animal models and translational clinical studies, the Musculoskeletal Project 2 (Drs. Weitzmann & Ofotokun) will test the hypothesizes that enhanced fracture risk observed in WLH is due to the collision between HIV/antiretroviral therapy (ART) induced inflammation and that induced by estrogen insufficiency as WLH age with ART. The goal of the Cardiovascular Project 3 (Drs. Quyyumi & Shaw) will be to assess the combined immune effects of HIV and estrogen status described in Project 1 & Project 2 on cardiovascular health as assessed by endogenous reparative/regenerative capacity (circulating progenitor cells) and the development/ progression of sub-clinical coronary (CT angiography) and carotid artery (MRI) atherosclerosis in WLH compared with HIV negative controls. All three projects will examine the same cohort of HIV infected women and HIV negative controls prospectively recruited from active participants at the NIH funded Atlanta WIHS.
Leveraging the robust research environment at Emory University, this application will explore the pathways underlying the influence of biological sex in the manifestations of infectious diseases using HIV as a model, with the hope of shedding additional light on the pathology and the pathogenesis underlying sex-mediated responses to chronic infections in order to enhance the development of interventions that take these factors into account. Through its leadership administrative and Career Enhancement cores, it will advance sex/gender science at Emory University and the Southeast region.