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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HD066439-04
Application #
8512760
Study Section
Special Emphasis Panel (ZHD1-DSR-L (08))
Program Officer
Ravindranath, Neelakanta
Project Start
2010-08-15
Project End
2015-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
4
Fiscal Year
2013
Total Cost
$273,139
Indirect Cost
$96,920
Name
Emory University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Yu, Jie; Berga, Sarah L; Zou, Wei et al. (2014) Gap junction blockade induces apoptosis in human endometrial stromal cells. Mol Reprod Dev 81:666-75
Pierzchalski, Keely; Taylor, Robert N; Nezhat, Ceana et al. (2014) Retinoic acid biosynthesis is impaired in human and murine endometriosis. Biol Reprod 91:84
Yu, Jie; Boicea, Anisoara; Barrett, Kara L et al. (2014) Reduced connexin 43 in eutopic endometrium and cultured endometrial stromal cells from subjects with endometriosis. Mol Hum Reprod 20:260-70
Reis, Fernando M; Petraglia, Felice; Taylor, Robert N (2013) Endometriosis: hormone regulation and clinical consequences of chemotaxis and apoptosis. Hum Reprod Update 19:406-18
Wu, Juanjuan; Taylor, Robert N; Sidell, Neil (2013) Retinoic acid regulates gap junction intercellular communication in human endometrial stromal cells through modulation of the phosphorylation status of connexin 43. J Cell Physiol 228:903-10
Wieser, Friedrich; Wu, Juanjuan; Shen, Zhaoju et al. (2012) Retinoic acid suppresses growth of lesions, inhibits peritoneal cytokine secretion, and promotes macrophage differentiation in an immunocompetent mouse model of endometriosis. Fertil Steril 97:1430-7