Grant: Operating Grant: ECI grants in Maternal, Reproductive, Child & Youth Health

Endometriosis is the presence of tissue from the lining of the uterus (womb) found outside the uterus. 10% of women will be affected by endometriosis during their childbearing years with ~1 million Canadian women affected in any given year. Symptoms can include daily pelvic pain, pain during menstruation or sexual activity, infertility and, in rare circumstances, development of ovarian cancer. The economic impact of endometriosis is ~$2 billion/yr in Canada and over $50 billion/yr in the USA, attributed to lost productivity and management of chronic disease. Nonetheless, it remains vastly understudied, leaving women with unanswered questions on how to deal with their disease and whether any treatment may be successful. Historically thought of as an inflammatory condition, endometriosis is classified based on where it presents: (1) on the ovary (endometrioma), (2) on the surface of peritoneal organs (superficial), or (3) invading into organs (deep endometriosis). Staging of endometriosis estimates the amount of disease present. Neither anatomical classes, nor staging, are reliable for predicting success of treatments or alleviation of symptoms. In 2017, my group reported a world-first discovery that 25% of endometriosis carry cancer-driver mutations despite having no risk of becoming cancer. We have since discovered that different types of endometriosis have similar mutations and some women with multiple types of endometriosis may have the exact same mutations across all lesions. Endometriosis symptoms and behavior must therefore depend on both mutations and interactions with normal cells in the body, e.g. organs and immune system. To accelerate research and drive development of new management strategies we propose to examine how mutations and anatomical presentation of endometriosis influence its interaction with normal cells in the body and the immune system (the microenvironment). This study will form the basis for a new molecular-classification of endometriosis.