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

描述(由申请人提供)：我们建议建立一个新的U01合作研究伙伴关系，以促进生殖科学中劳动力的多样性，以响应RFA-HD-09-008。亚特兰大子宫内膜异位症转化研究中心(ACTRE)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，将由欧盟医学博士罗伯特·N·泰勒和MSM博士温斯顿·E·汤普森联合指导。这些领导人是备受尊敬的独立调查人员，在协调的、多学科的生殖研究和教育团队中拥有丰富的经验和生产力。此外，该计划将由亚特兰大临床和翻译科学研究所提供的现有基础设施推动，该研究所自2007年以来一直由欧盟和MSM联合运营。NICHD的主题“细胞到自己”(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症的关系的生物学基础。ACTRE的科学焦点将集中在子宫内膜异位症细胞周期动力学的调控上，以确定子宫内膜异位症细胞凋亡为何失调，以及如何在治疗上诱导它。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。特别要强调的是核因子-βB和抑制素途径。原代细胞培养将使用泰勒博士开创的具有良好特性的方法进行开发。在Aim#2中，Thompson博士将使用这些培养物来测试荷尔蒙和非荷尔蒙凋亡诱导剂的效果，并使用mRNA图谱和2D-Gel磷酸蛋白质组学技术验证特定的细胞质和线粒体凋亡机制。目的#3将利用带有子宫内膜异位症样病变的大鼠，在体内测试旨在诱导病变细胞凋亡的新型治疗药物的疗效。这些学者将在临床上被介绍给患有子宫内膜异位症的妇女，并跟踪她们的子宫内膜标本到实验室，在那里将进行分子机制的研究。从疾病到可能的药物开发，不同的本科生干部将接触到整个翻译体验。来自欧盟和MSM的导师将指导学者进行临床和实验室研究、教学指导，并提供个性化的导师，目标是促进与生殖科学相关的研究生和专业课程的入学。 公共卫生相关性：子宫内膜异位症病变存活和抗凋亡的具体科学主题提供了一个有针对性的重点，让代表不足的少数族裔学生参与生殖科学研究的智力兴奋以及患有这种疾病的妇女未得到满足的临床需求。此外，Actre将在整个大亚特兰大生物医学研究联盟中促进对子宫内膜异位症的原因和可能的治疗方法的合作调查。

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. PUBLIC HEALTH RELEVANCE: The specific scientific theme of endometriotic lesion survival and resistance to apoptosis provides a targeted focus to engage underrepresented minority students about the intellectual excitement of reproductive science investigation and the unmet clinical needs of women suffering from this condition. Additionally, ACTRE will promote collaborative investigation into the causes and possible treatments of endometriosis across the greater Atlanta biomedical research consortium.