Center for Women's Health and Reproduction

描述(由申请者提供)：伊利诺伊大学SCCPRIR项目的持续目标将是进行对女性健康具有重要意义的创新基础和临床研究。提出了四个互动项目，以继续描绘狒狒模型和妇女中子宫内膜异位症的病因学和病理生理学，并解决与蜕膜和植入有关的关键问题。项目I(Fazleabas)将测试子宫内膜异位症改变在位内膜基因表达模式以及这些改变是表观遗传的假说。对CXCL12和糖蛋白的研究将提供对免疫系统中的异常的洞察。项目II(Bulun)“激素在子宫内膜异位症中的作用”将研究异位内膜基质细胞中ERβ增加的表观遗传学机制，并确定导致异位内膜基质细胞中ERα表达降低的转录机制。进一步的研究将确定雌激素下调子宫内膜异位症间质中PR基因表达的机制。翻译目标将把项目I和项目II联系起来，以测试选择性类固醇激素受体调节剂的治疗效果。项目III(NOWAK)“EMMPRIN调节子宫内膜的组织重塑”将研究EMMPRIN调节子宫内膜间质细胞蜕膜化的机制，以及EMMPRIN如何通过增加子宫内膜异位病变的血管生成和局部炎症反应来促进子宫内膜异位症的发展。项目四(LEACH)“人类植入中的EGF家族信号”将研究HB-EGF依赖的EGF受体反式激活滋养层细胞生存和转化为侵袭性表型所必需的潜在机制。这些项目将得到一个行政核心和两个研究核心的支持：A)成像和显微镜以及B)组织采购和细胞培养。这些研究核心将以开放获取模式运作，并支持美国国立卫生研究院批准的其他七项赠款，这些赠款的研究目标将有助于但不会违反U54申请的目标。伊利诺伊大学的U54中心将继续是一个强大的互动和合作环境，并在一个在生殖研究方面拥有丰富历史的机构内。

DESCRIPTION (provided by applicant): The continued objective of the SCCPRIR program at the University of Illinois will be to conduct innovative basic and clinical research that is of significance to Women's Health. Four interactive projects are proposed to continue to delineate the etiology and pathophysiology of endometriosis in the baboon model and in women as well as address critical questions relating to decidualization and implantation. Project I (Fazleabas) "Endometriosis in the Baboon" will test the hypothesis that endometriotic lesions alter gene expression patterns in eutopic endometrium and that these changes are epigenetic. In studies on CXCL12and glycodelin will provide insight into aberrations in the immune system. Project II (Bulun) "Hormone Action in Endometriosis" will investigate the epigenetic mechanisms for the ERbeta increase in endometriotic stromal cells and determine the transcriptional mechanism is responsible for the decreased ERalpha expression in endometriotic stromal cells. Additional studies will determine the mechanism responsible for down regulation of the PR gene by estradiol in endometriotic stroma. Translational aims will link Projects I and II to test the therapeutic effects of selective steroid hormone receptor modulators. Project III (Nowak) "EMMPRIN Regulates Tissue Remodeling in the Endometrium" will investigate the mechanisms by which EMMPRIN regulates decidualization of endometrial stromal cells and how EMMPRIN promotes the development of endometriosis by increasing angiogenesis and local inflammatory responses in endometriotic lesions. Project IV (Leach) "EGF Family Signaling in Human Implantation" will investigate the underlying mechanism of HB-EGF dependant EGF receptor transactivation in trophoblast necessary for survival and transformation to an invasive phenotype. These projects will be supported by an administrative core and two research cores: A) Imaging and Microscopy and B) Tissue Procurement and Cell Culture. These research cores will operate in an open access formula and support seven other NIH approved grants whose research objectives will contribute but will not infringe upon the goals of the U54 application. The U54 Center at the University of Illinois will continue to be a strong interactive and collegial environment and within an institution that has a rich history in reproductive research.