Grant: Project Grant

Endometriosis, characterized by growth of endometrial lining outside of the uterus, is the most prevalent global cause for hysterectomy, infertility and pelvic pain. It affects 6-10% of reproductive age women and 35-50% in women with pelvic pain/unexplained infertility. Despite its staggering economic impact ($1.8 Billion/year Canada; $22 Billion/year USA), endometriosis remains misdiagnosed, misunderstood and ineffectively treated. Diagnosis relies on invasive laparoscopy procedure to visualise lesions. Current treatments transiently alleviate but do not cure endometriosis. Growth of endometriotic lesions depend on abnormally levels of estrogen combined with pronounced inflammatory environment in the peritoneal cavity. Indeed, we provided striking evidence that endometriotic lesions are major regulators and promoters of inflammation. From our preliminary data and published papers, IL23-IL17 axis emerged as a major pathway in regulation of pain and inflammation. However mechanisms and molecular drivers of IL23-IL17 axis that modulate inflammation and pain in endometriosis is unidentified. Using endometriosis patient samples, cell lines and our established mouse models, we will: 1) Determine the basis for endometriosis associated immune dysfunction and how it contributes to susceptibility and progression of endometriosis.2) Identify and validate immune-inflammatory mediators (e.g., IL-17/IL-23 axis) contributing to the pathogenesis of endometriosis and for their diagnostic/therapeutic potential. 3) Conduct pre-clinical evaluation of IL-23-IL17 axis for therapeutic targeting in mouse model of endometriosis. Our research will provide novel insights into how complex immune networks are involved in the pathogenesis of endometriosis and deliver real-life solutions for improved diagnosis and better management of endometriosis patients.