Emory Specialized Center of Research Excellence (SCORE) on Sex Differences

埃默里大学性别差异专业卓越研究中心 (SCORE)

基本信息

批准号：
10231027
负责人：
Cecile Delille Lahiri
金额：
$ 149.22万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-30 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10231027
关键词：
Age Aging Amenorrhea Angiography Animal Model Antiviral Agents Atherosclerosis Biological Biomedical Research Biometry Bone Density Brain CCL2 gene Cardiovascular Diseases Cardiovascular system Carotid Arteries Centers of Research Excellence Cerebrovascular Disorders Cessation of life Chronic Clinical Research Communicable Diseases Coronary Development Disease Environment Estrogen Receptors Estrogens Exposure to Extramural Activities Female Female of child bearing age Fertility Rates Fostering Funding Gender Goals HIV HIV Infections HIV Seronegativity HIV antiretroviral Health Heart Immune Immune system Immunologic Deficiency Syndromes Immunology Impairment Inflammation Inflammatory Interdisciplinary Study Interferon Type II Interferons Interleukin-1 beta Interleukin-6 Ischemic Stroke Leadership Light Magnetic Resonance Imaging Matrix Metalloproteinases Mediating Menopause Modeling Musculoskeletal Myocardial Infarction NOS2A gene Natural Killer Cells Organ Outcome Ovarian Participant Pathogenesis Pathology Pathway interactions Policies Post-Traumatic Stress Disorders Postmenopause Pregnancy Premenopause Production Recruitment Activity Regenerative capacity Reporting Research Research Personnel Research Project Grants Research Support Resources Risk Risk Factors Science Services Sex Differences Specialized Center Stem Cell Development Stress TNF gene Testing Translational Research United States National Institutes of Health Universities Vision Woman Women&apos s Health age related antiretroviral therapy biological sex bone cardiovascular health career career development chronic infection cohort comorbidity data management drug development early experience early onset experience fracture risk high risk hypothalamic-pituitary-adrenal axis immune activation improved microbial host nervous system disorder pathogen programs prospective response sex social synergism therapy development

项目摘要

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.

埃默里 SCORE 的总体目标是通过利用埃默里大学丰富、协作和跨学科的研究环境有利于 NIH 和其他机构的发展外部资助的女性健康研究的长期愿景是在埃默里大学开发一个项目作为研究生物性别对传染病结果影响的区域中心并促进性别作为研究中的生物变量的正常化，以改善这些目标将通过 a) 实施 3 个跨领域研究项目来实现。采用“HIV-宿主病原体相互作用”作为探讨性别对病理学影响的模型传染病的发病机制； b) 领导行政核心 (LAC) 的发展；建立职业发展核心（CEC），以促进在以下领域工作的初级研究人员的职业发展妇女健康研究；和 d) 生物统计资源核心 (BRC)，以优化所有 SCORE 的严格性我们对传染病的关注凸显了这些疾病的全球负担。妇女，与 NIH 妇女健康研究办公室 (OWHR) 的优先事项保持一致，并利用埃默里大学的研究优势在于艾滋病毒转化研究、基础免疫学和抗病毒药物开发。这三个研究项目将探索艾滋病毒诱导的免疫激活与慢性病之间的协同作用炎症以及在感染艾滋病毒的老年女性中观察到的由雌激素不敏感引起的炎症。我们推测神经下丘脑垂体肾上腺 (HPA) 轴项目 1（Drs. Neigh 和 Michopoulos） HIV 与多种因素相互作用，包括压力暴露降低全身雌激素水平和下调雌激素受体的细胞表达，从而产生相对雌激素不足状态感染艾滋病毒的女性 (WLH) 的慢性炎症随之加剧。模型和转化临床研究，肌肉骨骼项目 2（Weitzmann 博士和 Ofotokun 博士）将测试捕获结果，发现在 WLH 中观察到的骨折风险增加是由于之间的碰撞 HIV/抗逆转录病毒治疗 (ART) 引起的炎症以及雌激素不足引起的炎症与 WLH 年龄有关心血管项目 3（Quyyumi 博士和 Shaw）的目标是评估合并后的结果。项目 1 和项目 2 中描述的 HIV 和雌激素状态对心血管健康的免疫影响为通过内源性修复/再生能力（循环祖细胞）和发育/ WLH 中亚临床冠状动脉进展（CT 血管造影）和颈动脉 (MRI) 动脉粥样硬化的影响与艾滋病毒阴性对照相比，所有三个项目都将检查同一组艾滋病毒感染妇女。艾滋病毒阴性对照是从 NIH 资助的亚特兰大 WIHS 的活跃参与者中前瞻性招募的。