Reproductive Endocrinology And Infertility Clinical Training Program

子宫肌瘤 到生育年龄结束时，美国超过50%的女性患上子宫肌瘤，使其成为女性最普遍的生殖障碍。尽管这种疾病普遍存在，但人们对这种疾病的了解仍然很少。子宫肌瘤的一个突出特征是肿瘤内的细胞产生紊乱和过量的细胞外基质（ECM）。以前，我们已经检查了ECM和产生这种过度和纤维化ECM的细胞的特征，并发现机械信号（细胞通讯和激活的方法）在肌瘤内的细胞中发生了改变。我们目前的研究重点是如何利用这种改变的机械信号状态来开发肌瘤的非手术治疗方法。 BRX（也称为AKAP 13）在心脏发育，免疫功能和生殖中的作用 我们以前的研究基因BRX（AKAP 13），由我们的小组克隆，表明这个大的Rho-GEF原癌蛋白参与雌激素和糖皮质激素受体的激活。我们以前发现，BRX基因产物协调G-亚-α-s和Rho信号转导与小鼠心肌细胞发育中的一个重要转录程序，涉及肌细胞增强因子2C（MEF 2C）。AKAP 13基因（敲除）有两个缺陷拷贝的小鼠在子宫内死亡。在过去的一年中，我们已经开发了一种条件基因打靶策略，使用Cre-Lox系统在小鼠和检查表型的条件靶向后代。我们发现，条件性基因敲除小鼠在Cre激活发生之前没有表现出心功能障碍，之后小鼠出现心输出量减少和提示扩张型心肌病的功能特征。 在接下来的一年里，我们将继续研究AKAP 13在心脏病体内模型中的作用。此外，我们将扩大我们的分析AKAP 13在生殖组织中的作用，使用Cre-Lox策略与生殖道特异性策略激活Cre重组酶。

Uterine leiomyoma By the end of their reproductive years, over 50% of women in the United States develop uterine fibroids, making the condition the most prevalent reproductive disorder of women. Despite their prevalence, the condition remains poorly understood. One prominent feature of uterine fibroids is that cells within the tumors produce a disordered and excessive extracellular matrix (ECM). Previously, we have examined the ECM and characteristics of the cells that produce this excessive and fibrotic ECM and have found that mechanical signaling (a method of cell communication and activation) was altered in cells within a fibroid. Our current research focuses on how this altered state of mechanical signaling might be utilized to develop non-surgical treatments for fibroids. Role of BRX (also known as AKAP13) in cardiac development, immune function and reproduction Our previous studies of the gene BRX (AKAP13), cloned by our group, indicated that this large Rho-GEF protooncoprotein was involved in estrogen and glucocorticoid receptor activation. We previously found that the BRX gene product coordinates G-sub-alpha-s and Rho signaling with an essential transcription program in developing cardiomyocytes in mice, involving myocyte enhancer factor 2 C (MEF2C). Mice with two defective copies of the AKAP13 gene (knockout) died in utero. In the past year we have developed a conditional gene targeting strategy using the Cre-Lox system in mice and examined phenotypes of the conditionally-targeted offspring. We found that mice with the conditional knockout did not exhibit cardiac dysfunction until Cre activation occurred, after which the mice developed reduced cardiac output and functional features suggestive of dilated cardiomyopathy. In the coming year we will continue to examine the role of AKAP13 in this in vivo model of cardiac disease. Further, we will expand our analysis of the role of AKAP13 in reproductive tissues using the Cre-Lox strategy with reproductive-tract-specific strategies for activation of Cre recombinase.