Endometriosis is a common gynecologic disease involving endometrial tissue located outside of the uterine cavity. It causes debilitating pain and frustrating infertility in women with this disease. Despite extensive nvestigation, no study has shown a specific gene involved in endometriosis, but a genetic predisposition is likely. To define the molecular profile of women with endometriosis, we have recruited 84 endometriosis cases in the Houston area and 47 control patients. Genomic DMA is being analyzed by comparative genomic hybridization using the Agilent platform, mRNA levels are analyzed with Illumina microarrays, and microRNAs by the Illumina/Solexa sequencing platform. The overall hypothesis for this project is that regulatory defects in microRNAs play a central early role in organizing the molecular changes involved in endometriosis and, in doing so, determine important aspects of its clinical behavior and response to therapy.
The specific aims of the project involve identifying microRNA regions in genomic DNA associated with endometriosis, profiling microRNA signatures of normal endometrium and endometriotic tissues, validating microRNA:mRNA targets, and creating in vitro models for studying the role of candidate microRNAs in uterine function and dysfunction. Our proposed research will allow us to develop cost-effective, highthroughput strategies for classifying individual patients with endometriosis at a molecular (microRNA, mRNA, and genomic) level with the long-term goal of developing patient-specific treatment protocols.

Public Health Relevance

Endometriosis is a devastating disease to women, involving pain, decreased quality of life, and infertility. Currently, accurate diagnosis requires surgery and treatment protocols are grossly ineffective long term. The goals of our studies are to develop a molecular signature for each patient with endometriosis that can be used diagnostically to assess prognosis and develop novel therapeutic interventions.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54HD007495-39
Application #
8375883
Study Section
Special Emphasis Panel (ZHD1-DSR-L)
Project Start
Project End
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
39
Fiscal Year
2012
Total Cost
$226,134
Indirect Cost
$66,372
Name
Baylor College of Medicine
Department
Type
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Piyarathna, Danthasinghe Waduge Badrajee; Rajendiran, Thekkelnaycke M; Putluri, Vasanta et al. (2018) Distinct Lipidomic Landscapes Associated with Clinical Stages of Urothelial Cancer of the Bladder. Eur Urol Focus 4:907-915
Choi, Byung-Kwon; Dayaram, Tajhal; Parikh, Neha et al. (2018) Literature-based automated discovery of tumor suppressor p53 phosphorylation and inhibition by NEK2. Proc Natl Acad Sci U S A 115:10666-10671
Parikh, Neha; Shuck, Ryan L; Gagea, Mihai et al. (2018) Enhanced inflammation and attenuated tumor suppressor pathways are associated with oncogene-induced lung tumors in aged mice. Aging Cell 17:
Kotlajich, Matthew V; Xia, Jun; Zhai, Yin et al. (2018) Fluorescent fusions of the N protein of phage Mu label DNA damage in living cells. DNA Repair (Amst) 72:86-92
Szafran, Adam T; Stossi, Fabio; Mancini, Maureen G et al. (2017) Characterizing properties of non-estrogenic substituted bisphenol analogs using high throughput microscopy and image analysis. PLoS One 12:e0180141
Ha, Kyungsoo; Ma, Chengxian; Lin, Han et al. (2017) The anaphase promoting complex impacts repair choice by protecting ubiquitin signalling at DNA damage sites. Nat Commun 8:15751
Roarty, K; Pfefferle, A D; Creighton, C J et al. (2017) Ror2-mediated alternative Wnt signaling regulates cell fate and adhesion during mammary tumor progression. Oncogene 36:5958-5968
Aagaard, Kjersti M; Lahon, Anismrita; Suter, Melissa A et al. (2017) Primary Human Placental Trophoblasts are Permissive for Zika Virus (ZIKV) Replication. Sci Rep 7:41389
Szafran, Adam T; Stephan, Cliff; Bolt, Michael et al. (2017) High-Content Screening Identifies Src Family Kinases as Potential Regulators of AR-V7 Expression and Androgen-Independent Cell Growth. Prostate 77:82-93
Tsai, Wei-Chih; Reineke, Lucas C; Jain, Antrix et al. (2017) Histone arginine demethylase JMJD6 is linked to stress granule assembly through demethylation of the stress granule-nucleating protein G3BP1. J Biol Chem 292:18886-18896

Showing the most recent 10 out of 159 publications