Center for Endometrial Biology and Endometriosis

描述（由申请人提供）：本申请申请在耶鲁大学和范德比尔特大学建立一个专门的生殖研究合作中心，命名为“子宫内膜生物学和子宫内膜异位症中心”。子宫内膜紊乱和子宫内膜异位症导致不孕、子宫异常出血、盆腔疼痛和痛经等显著的发病率。子宫内膜异位症影响10-15%的育龄妇女和高达50%的不孕妇女。子宫内膜紊乱是一个具有广泛公共卫生影响的常见问题。尽管这些疾病普遍存在，但在了解这些疾病及其治疗方面进展甚微。治疗依赖于激素控制，充满了副作用和治疗失败。本应用的中心主题是发现子宫内膜疾病和子宫内膜异位症的新机制和治疗靶点。在初步数据的支持下，每个项目都假设了一种涉及该组织病因或生长的新的调节机制，并建议或测试了新的治疗方法。该中心由三个核心协作和支持。五个互动研究项目解决了这一假设的核心要素。项目一将描述子宫内膜移植和子宫内膜异位症与转分化骨髓源性干细胞。该项目将确定骨髓产生子宫内膜的程度，潜在的机制和功能后果。项目二将探讨组织因子在子宫内膜生长调节中的作用。巨噬细胞衍生的组织因子有助于子宫内膜的生长，并且可以被一种新的靶向组织因子的免疫共轭分子（ICON）阻断。项目III将研究黄体酮在子宫内膜异位症中的作用失败，原因是涉及上皮显性细胞-细胞通信、TGF - β和类视黄醛信号的新途径被破坏。IV项目将进一步确定甲羟戊酸途径在子宫内膜基质细胞生长中的作用，并测试他汀类药物作为子宫内膜生长抑制剂的新用途。项目V是一个试点项目，旨在探索子宫内膜异位症中招募巨噬细胞的趋化因子，并测试传统和新型治疗方法对信号转导的影响。该中心还包含三个核心。管理核心，细胞和组织核心和小鼠建模核心将由每个研究人员使用，并完成一个综合中心。

DESCRIPTION (provided by applicant): This application requests funding for the establishment of a Specialized Cooperative Center in Reproductive Research at Yale and Vanderbilt Universities to be named "The Center for Endometrial Biology and Endometriosis." Disorders of the endometrium and endometriosis result in significant morbidity including infertility, abnormal uterine bleeding, pelvic pain and dysmenorrhea. Endometriosis affects 10-15% of reproductive aged women and up to 50% of women with infertility. Endometrial disorders are a common problem with wide-spread public health implications. Despite the prevalence of these disorders, little progress had been made in understanding these conditions or their treatment. Therapy relies on hormonal manipulation and is fraught with side effects and treatment failures. The central theme of this application is discovery of novel mechanisms and therapeutic targets for endometrial disease and endometriosis. Each project, supported by preliminary data, hypothesizes a novel regulatory mechanism involved in the etiology or growth of this tissue, as well as suggests or tests novel therapies. The Center is collaborative and supported by three cores. Five interactive research projects address the central elements of this hypothesis. Project I will characterize the engraftment of endometrium and endometriosis with transdifferentiated bone marrow-derived stem cells. This Project will determine the extent to which bone marrow gives rise to the endometrium, the underlying mechanisms and functional consequences. Project II will explore the role of tissue factor in regulation of endometrial growth. Macrophage derived tissue factor contributes to endometrial growth and can be blocked by a novel immunoconjugated molecule (ICON) that targets tissue factor. Project III will look at failure of progesterone action in endometriosis due to disruption of a novel pathway involving epithelial- dominant cell-cell communication and TGF beta as well as retinoid signaling. Project IV will further determine the role of the mevalonate pathway on endometrial stromal cell growth and tests the novel use of statins as inhibitors of endometrial growth. Project V is a pilot project that explores the chemokines that recruit macrophages in endometriosis and tests the effects of traditional and novel treatments discovered here on signal transduction. The Center also contains three Cores. An Administrative Core, a Cell and Tissue Core and Mouse Modeling Core will be used by each of the investigators and complete a comprehensive Center.