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)

• 批准号: 9790907
• 负责人: Lisa Blake Haddad
• 金额: $ 149.82万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 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/9790907
• 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; Comorbidity; 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; Reporting; Research; Research Personnel; Research Project Grants; Research Support; Resources; Risk; Risk Factors; Science; Services; Sex Differences; Specialized Center; Stem cells; Stress; TNF gene; Testing; Translational Research; United States National Institutes of Health; Universities; Vision; Woman; Women' s Health; age related; antiretroviral therapy; biological sex; bone; cardiovascular health; career; career development; chronic infection; cohort; 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; regenerative; response; sex; social; synergism; therapy development

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 外部资助的妇女健康研究。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 女性健康。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 和传染病的发病机制； b) 建立领导行政核心（LAC）； c) 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； d) 生物统计资源核心 (BRC)，以优化所有 SCORE 的严格性 支持的研究。我们对传染病的关注凸显了这些疾病在全球造成的负担 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 在感染艾滋病毒的老年女性中观察到炎症和雌激素不敏感引起的炎症。在 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。使用基本动物 模型和转化临床研究，肌肉骨骼项目 2（Weitzmann 博士和 Ofotokun 博士）将 检验以下假设：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 与艺术。心血管项目 3（Quyyumi 博士和 Shaw 博士）的目标是评估综合 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（CT 血管造影）和颈动脉（MRI）动脉粥样硬化的进展 与 HIV 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 HIV 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。