We propose a new U01 Cooperative Research Partnership to Promote Workforce Diversity in the Reproductive Sciences in response to RFA-HD-09-008. The Atlanta Center for Translational Research in Endometriosis (ACTRE, pronounced """"""""actor"""""""") is a partnership between the reproductive research programs of Emory University (EU) and Morehouse Schools of Medicine (MSM) and will be jointly directed by Robert N. Taylor, MD, PhD of EU and Winston E. Thompson, PhD of MSM. The leaders are highly respected independent investigators with extensive experience and productivity in coordinated, multidisciplinary reproduction research and education teams. Moreover, the program will be facilitated by extant infrastructure provided under the aegis of the Atlanta Clinical and Translational Science Institute, which has been jointly operated between EU and MSM since 2007. The NICHD theme of """"""""cells to selves"""""""" (NIH Guide, January 30, 2002) serves as the biological foundation to study the fundamental mechanisms of endometriosis lesion growth and apoptosis and their relationship to pain and infertility. The scientific focus of ACTRE will concentrate on the regulation of endometriotic cell cycle dynamics to determine why endometriotic cell apoptosis is dysregulated and how might it be therapeutically induced.
Aim #1 will identify specific survival factor pathways in tissue specimens from women with and without endometriosis. In particular, the NF-?B and prohibitin pathways will be emphasized. Primary cell cultures will be developed using well characterized methods pioneered by Dr. Taylor.
In Aim #2, Dr. Thompson will use these cultures to test the effects of hormonal and nonhormonal apoptosis-inducing agents and validate specific cytoplasmic and mitochondrial mechanisms of apoptosis using mRNA profiling and 2D-gel phosphoproteomic techniques.
Aim #3 will utilize rats bearing endometriosis-like lesions to test the efficacy of novel therapeutic agents designed to induce apoptosis in the lesions in vivo. The Scholars will be introduced in the clinic to women suffering from endometriosis and follow their endometrial specimens to the laboratory, where investigation of molecular mechanisms will take place. A diverse cadre of undergraduates will be exposed to the entire translational experience, from disease to possible drug development. Mentors from EU and MSM will guide scholars in clinical and laboratory research, didactic instruction, and provide individualized mentorship with the goal of facilitating matriculation in graduate and professional programs related to reproductive sciences.
The specific scientific theme of endometriotic lesion survival and resistance to apoptosis provides a targeted focus to engage underrepresented minority students about the intellectual excitement of reproductive science investigation and the unmet clinical needs of women suffering from this condition. Additionally, ACTRE will promote collaborative investigation into the causes and possible treatments of endometriosis across the greater Atlanta biomedical research consortium.
|Wu, Juanjuan; Williams, Devin; Walter, Grant A et al. (2014) Estrogen increases Nrf2 activity through activation of the PI3K pathway in MCF-7 breast cancer cells. Exp Cell Res 328:351-60|
|Chowdhury, Indrajit; Thompson, Winston E; Welch, Crystal et al. (2013) Prohibitin (PHB) inhibits apoptosis in rat granulosa cells (GCs) through the extracellular signal-regulated kinase 1/2 (ERK1/2) and the Bcl family of proteins. Apoptosis 18:1513-25|