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

描述（由申请人提供）：我们提出了一个新的U 01合作研究伙伴关系，以促进生殖科学的劳动力多样性，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，发音为“演员”）是埃默里大学（欧盟）和莫尔豪斯医学院（MSM）生殖研究项目之间的合作伙伴关系，将由罗伯特N。泰勒，医学博士，欧盟博士和温斯顿E。汤普森，MSM博士。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拥有丰富的经验和生产力。此外，该计划将得到亚特兰大临床和转化科学研究所支持下提供的现有基础设施的促进，该研究所自2007年以来一直由欧盟和男男性行为者联合运营。NICHD的“细胞自我”主题（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的科学重点将集中在肿瘤细胞周期动力学的调节，以确定为什么肿瘤细胞凋亡失调，以及如何治疗诱导。目的#1将确定来自患有和不患有子宫内膜异位症的妇女的组织标本中的特定生存因子途径。尤其是NF-？B和抑制素途径将被强调。原代细胞培养物将使用Taylor博士开创的良好表征的方法进行开发。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促凋亡剂的作用，并使用mRNA分析和2D凝胶磷酸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将利用具有类神经纤维瘤病变的大鼠来测试设计用于在体内病变中诱导细胞凋亡的新型治疗剂的功效。学者们将在诊所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干部将接触到整个翻译经验，从疾病到可能的药物开发。来自欧盟和男男性接触者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课程的入学。 公共卫生相关性：特定的肿瘤病变生存和抗细胞凋亡的科学主题提供了一个有针对性的重点，让代表性不足的少数民族学生了解生殖科学调查的智力兴奋和患有这种疾病的妇女未满足的临床需求。此外，ACTRE将促进对整个大亚特兰大生物医学研究联盟的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.