Reproductive Endocrinology And Infertility Clinical Training Program

生殖内分泌与不孕不育临床培训项目

• 批准号: 8941580
• 负责人: James H. Segars
• 金额: $ 80.51万
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8941580
• 关键词: AKAP13 gene; Cardiac; Cardiac Myocytes; Cardiac Output; Cell Communication; Cells; Characteristics; Clinical; Clinical Research; Cre-LoxP; Development; Dilated Cardiomyopathy; Disease; Estrogen Receptors; Exhibits; Extracellular Matrix; Fellowship Program; Fibroid Tumor; Functional disorder; Gene Targeting; Genetic Transcription; Glucocorticoid Receptor; Heart Diseases; Infertility; Knock-out; Mechanics; Methods; Mus; National Institute of Child Health and Human Development; Phenotype; Prevalence; Proteins; Receptor Activation; Reproduction; Reproductive Endocrinology; Research; Role; Signal Transduction; System; Tissues; Training Programs; United States; Uterine Fibroids; Woman; clinically relevant; endometriosis; health disparity; immune function; in utero; in vivo Model; myocyte-specific enhancer-binding factor 2; offspring; programs; recombinase; reproductive; rho; tumor

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.

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