GREB1 Action in Endometrial Function and Dysfunction

GREB1 在子宫内膜功能和功能障碍中的作用

• 批准号: 9049524
• 负责人: Ramakrishna Kommagani
• 金额: $ 11.07万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-15 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9049524
• 关键词: Address; Advanced Development; Androgens; Biochemical; Cell physiology; Cells; Clinical; Clinical Management; Decidual Cell; Decidual Cell Reactions; Diagnosis; Diagnostic; Embryo; Endometrial; Endometrial Disorder; Endometrial Stromal Cell; Endometriomas; Endometrium; Engineering; Estrogens; Failure; Female infertility; Foundations; Functional disorder; Future; Genes; Genetic Transcription; Genomic approach; Gonadal Steroid Hormones; Growth; Health; Human; Infertility; Knowledge; Lead; Link; Mediating; Mentors; Modeling; Molecular; Molecular Target; Mus; Natural regeneration; Nuclear Receptors; Outcome; Pathogenesis; Pathology; Patients; Phase; Physiology; Process; Progesterone; Progesterone Receptors; Regulation; Reporting; Reproductive Health; Role; Science; Signal Pathway; Spontaneous abortion; Staging; Stromal Cells; Tissues; Training; Transcriptional Regulation; Uterus; Woman; Work; Xenograft procedure; base; blastocyst; career; career development; endometriosis; failure Implantation; functional genomics; genome-wide analysis; implantation; in vivo; innovation; insight; malignant breast neoplasm; mouse model; natural Blastocyst Implantation; overexpression; programs; prostate cancer cell; reconstitution; reproductive; response; steroid hormone; translational study

 DESCRIPTION (provided by applicant): Even when the blastocyst develops normally, inadequate differentiation of stromal cells to decidual cells in the endometrium (termed decidualization) can lead to implantation failure or early embryo miscarriage. Although many of the cellular mechanisms that underpin steroid-hormone actions in endometrial physiology are well defined, a significant knowledge-gap exists concerning the coregulator and signaling pathways that control or mediate steroid-hormone responses in the decidualization process. This knowledge-gap is significant as without new mechanistic insights into this aspect of embryo implantation, the ability to diagnose and/or treat infertility based on a functionally impaired endometrium will not be realized. Recently, I identified GREB1 as a progesterone responsive gene and critical for the induction of progesterone molecular targets required for decidualization of primary human endometrial stromal cells in culture. Therefore, this finding implicates a coactivator role for GREB1 in this cellular process. In parallel studies, I also showed that GREB1 is required for estrogen-driven proliferation of endometrioma cells derived from endometriosis patients, indicating a separate role for GREB1 in estrogen-dependent endometriosis. Based on my preliminary observations, I hypothesize that the coactivator function of GREB1 is required both for progesterone-driven endometrial decidualization and for estrogen-dependent endometriosis progression. Therefore, my proposal plans to examine the dual role of GREB1 in endometrial function and dysfunction. The K99 phase will establish the in vivo role of GREB1 in normal endometrial responses to progesterone exposure using a recently engineered mouse model. These studies will transition into the R00 portion, which uses this model to define the pathogenic importance of GREB1 in estrogen-driven endometriosis. The R00 phase will also determine the molecular mechanism that underpins the coactivator function of GREB1 in progesterone-driven human endometrial decidualization. Combined with career development training, which will include mentoring, course work, and presentation opportunities, these studies will extend my training in endometrial physiology and pathophysiology to provide a strong foundation to launch an independent career in the reproductive sciences in near future.



项目成果

Application of 13C isotope labeling using liquid chromatography mass spectrometry (LC-MS) to determining phosphate-containing metabolic incorporation.

• DOI: 10.1002/jms.3292
• 发表时间: 2013
• 期刊: Journal of mass spectrometry : JMS
• 作者: S. K. Bhowmik;V. Putluri;R. Kommagani;S. A. Konde;J. Lydon;A. Sreekumar;N. Putluri