Roles of Hippo signaling and gap junctional communication in follicle development

点击翻译按钮获取中文摘要

The following application is intended to initiate the research career of Dr. Kendra L. Clark under the mentorship of Dr. John S. Davis. Dr. Clark received her PhD in Genetics and Genomics in December 2019 and is currently completing her postdoctoral training focused exclusively on reproductive health research, specifically in regulation of early follicle development and cellular communication. Dr. Davis is an outstanding reproductive biologist, has had extensive experience in training researchers at various levels, and has been funded through the NIH, USDA, and VA for the past 30 years. Environment - The University of Nebraska Medical Center (UNMC) is a leading academic health and research center that bridges the gap between research and applied medicine, harboring collaborative efforts between basic and translational research teams and medical professionals. Further, UNMC is adjacent to the Omaha VA Medical Center and within 40 minutes of University of Nebraska - Lincoln. The environment at UNMC, the VA, and UNL provides abundant opportunity for collaboration and research. Research - The ovary produces the female egg, the oocyte, and hormones which are critical for reproduction and quality-of-life. The Hippo signaling pathway controls organ size by regulating cell growth, death, and self-renewal. Recent studies demonstrate that YAP, a main component of the Hippo pathway, plays an important role in the ovary. The formation and maturation of follicles is a cellular transition process dependent on the formation of gap junctions, connections that allow passage of small molecules between cells. There is a lack of knowledge in the contribution of the Hippo pathway in early follicle development and the relationship with gap junction intercellular communication (GJIC). Experiments in this proposal are designed to test the hypothesis that (1) activation of Yap in somatic cells stimulates the early stages of follicle development and (2) alterations in Yap adversely impacts GJIC in the developing follicle. In this proposal we will utilize a tractable in vivo mouse model to study follicle development and a transgenic mouse model combined with advanced microscopy techniques to measure communication between cells. The goal of this research is to discover how Hippo signaling events and the interactions with cellular junctions in the follicle contribute to follicle development and oocyte growth. Outcomes for Fellowship Training - My current research objectives are to determine the contribution of the Hippo pathway in early follicular development and the relationship with gap junction intercellular communication (GJIC). My long-term research goal is to develop into an independent researcher with a focus on the molecular mechanisms responsible for environmentally-induced reproductive failure.