SIRT1 and BCL6: Dual Biomarkers of Endometriosis and Endometrial Receptivity

PROJECT SUMMARY ABSTRACT Endometriosis is a common and poorly understood disease affecting millions of women around the worldThe impact on fertility and pelvic pain is estimated to cost $billion dollarsbut this does not include the costs to treat IBSinterstitial cystitis and the cost of failed Assisted Reproductive TechnologyARTcyclesIt is estimated thatof failed ART cycles are due to undiagnosed endometriosisand most women undertaking ART have never been testedThis proposal is based on established technology that detects all stages of endometriosisBased on published resultswomen who over express the oncogene BCLhave areduction in live birth rate compared to women with normal BCLThis proposal will develop this technologyvalidate these findings and pursue a less invasive test formatAims including those in Phase Iwhich will validate and examine a second co expressed biomarkerSirtuinSIRTpresent in endometriosis cases at all phases of the menstrual cycle in women with documented endometriosisThis first phase will also study expression of SIRTand BCLin alternative tissue sources including bloodsalivaurineand cervical mucous using ELISA technologyAims in Phase II will examine expression of BCLand or SIRTas predictors of pregnancy outcomes in at a major IVF centerIn women who test positive for SIRTBCLwith suspected endometriosisa second multi center study will examine whether suppression of endometriosis with a novelnewly approved GnRH agonistElagolixfollowed by embryo transfer will improve outcomesFinallythe team will developvalidateand commercialize a reference laboratory test for endometriosis and endometrial receptivity using less invasive approaches for measuring SIRT or BCLbased on Phase I resultsThe final validation of a reference laboratory test will involve prospective testing before laparoscopy for pelvic pain or infertilitycases and infertile controlsand for women with fertility undergoing tubal ligation for permanent sterilizationfertile controlsWith this approach the sensitivityspecificityand negative and positive predictive value can be definedThe goal for this project is to establish a validated newless invasivetest for endometriosis bythat will allow all physicians treating women to shorten the time to diagnosis for endometriosis in a variety of clinical settings including pelvic paininfertilityirritable bowel syndrome and other pelvic complaints PROJECT NARRATIVE A validated test for endometriosis with clinical relevance is currently not availableInflammation is a defining characteristic of endometriosis and is associated with pain and infertilityand directly promotes the expression of two co expressed biomarker proteinsBCLand SIRTthat are used for the diagnosis of endometriosisThese proteins directly alter the actions of the hormone progesteronewhich is essential for pregnancycontributing to the pathophysiology of this disease and the infertility that women with endometriosis experienceThe goal of this project is to translate new discoveries based on these proteins into a rapidless invasive test for endometriosis that will be available for all women