1/2-Atlanta Center for Translational Research in Endometriosis (ACTRE)

描述（由申请人提供）：为响应RFA-HD-09-008，我们提议建立一个新的U01合作研究伙伴关系，以促进生殖科学领域的劳动力多样性。亚特兰大子宫内膜异位症转化研究中心（ACTRE，发音为“actor”）是埃默里大学（EU）和莫尔豪斯医学院（MSM）生殖研究项目的合作伙伴关系，将由EU医学博士Robert N. Taylor医学博士和MSM医学博士Winston E. Thompson共同指导。领导者是备受尊敬的独立调查员，在协调的多学科生殖研究和教育团队中具有丰富的经验和生产力。此外，该计划将由亚特兰大临床和转化科学研究所提供的现有基础设施提供便利，该研究所自2007年以来一直由EU和MSM共同运营。NICHD的主题“细胞自我”（NIH指南，2002年1月30日）是研究子宫内膜异位症病变生长和凋亡的基本机制及其与疼痛和不孕的关系的生物学基础。ACTRE的科学重点将集中在子宫内膜异位症细胞周期动力学的调节上，以确定子宫内膜异位症细胞凋亡失调的原因以及如何通过治疗诱导。目的1将在患有和不患有子宫内膜异位症的妇女的组织标本中确定特定的生存因子途径。特别是NF-？B和禁止途径将得到强调。原代细胞培养将采用泰勒博士开创的方法进行。在目标#2中，Thompson博士将使用这些培养物来测试激素和非激素细胞凋亡诱导剂的效果，并使用mRNA分析和2d凝胶磷酸化蛋白质组学技术验证细胞凋亡的特定细胞质和线粒体机制。目的3将利用患有子宫内膜异位症样病变的大鼠来测试新型治疗药物在体内诱导病变细胞凋亡的效果。这些学者将被介绍给患有子宫内膜异位症的妇女，并将她们的子宫内膜标本带到实验室，在那里将进行分子机制的研究。一个多样化的本科生骨干将接触到整个转化经验，从疾病到可能的药物开发。来自EU和MSM的导师将指导学者进行临床和实验室研究，教学指导，并提供个性化的指导，以促进与生殖科学相关的研究生和专业项目的入学。

DESCRIPTION (provided by applicant): We propose a new U01 Cooperative Research Partnership to Promote Workforce Diversity in the Reproductive Sciences in response to RFA-HD-09-008. The Atlanta Center for Translational Research in Endometriosis (ACTRE, pronounced "actor") is a partnership between the reproductive research programs of Emory University (EU) and Morehouse Schools of Medicine (MSM) and will be jointly directed by Robert N. Taylor, MD, PhD of EU and Winston E. Thompson, PhD of MSM. The leaders are highly respected independent investigators with extensive experience and productivity in coordinated, multidisciplinary reproduction research and education teams. Moreover, the program will be facilitated by extant infrastructure provided under the aegis of the Atlanta Clinical and Translational Science Institute, which has been jointly operated between EU and MSM since 2007. The NICHD theme of "cells to selves" (NIH Guide, January 30, 2002) serves as the biological foundation to study the fundamental mechanisms of endometriosis lesion growth and apoptosis and their relationship to pain and infertility. The scientific focus of ACTRE will concentrate on the regulation of endometriotic cell cycle dynamics to determine why endometriotic cell apoptosis is dysregulated and how might it be therapeutically induced. Aim #1 will identify specific survival factor pathways in tissue specimens from women with and without endometriosis. In particular, the NF-?B and prohibitin pathways will be emphasized. Primary cell cultures will be developed using well characterized methods pioneered by Dr. Taylor. In Aim #2, Dr. Thompson will use these cultures to test the effects of hormonal and nonhormonal apoptosis-inducing agents and validate specific cytoplasmic and mitochondrial mechanisms of apoptosis using mRNA profiling and 2D-gel phosphoproteomic techniques. Aim #3 will utilize rats bearing endometriosis-like lesions to test the efficacy of novel therapeutic agents designed to induce apoptosis in the lesions in vivo. The Scholars will be introduced in the clinic to women suffering from endometriosis and follow their endometrial specimens to the laboratory, where investigation of molecular mechanisms will take place. A diverse cadre of undergraduates will be exposed to the entire translational experience, from disease to possible drug development. Mentors from EU and MSM will guide scholars in clinical and laboratory research, didactic instruction, and provide individualized mentorship with the goal of facilitating matriculation in graduate and professional programs related to reproductive sciences.