Investigating how somatic mutation induced changes in the eutopic endometrial microenvironment cause endometriosis

forthcoming

Endometriosis is characterized by the presence of endometrium-like tissue outside the uterus and chronic inflammation. Worldwide, >10% of reproductive-age women suffer from pain and/or infertility caused by this disease. Recently, cancer driver mutations have been identified in both the eutopic and ectopic endometrium of endometriosis patients. Moreover, it has been shown in cancer studies that cancer driver mutations can alter the local immune microenvironment. Nevertheless, it has never been studied how cancer driver mutations present in the eutopic endometrium of endometriosis patients contribute to the pathogenesis of this disease. Therefore, I propose to investigate how these mutations that are present in the eutopic endometrium alter the local eutopic immune microenvironment and thereby drive endometriosis development. This theory is what the acronym MERMAID in this proposal stands for: Mutations in Endometrial Regions and Microenvironmental Adaptations Influence Disease. To this end, I will analyze cell viability and immune cell signature in the menstrual fluid of people with and without endometriosis and identify which cancer driver mutations are present in their endometrial epithelial cells. In addition, I will create a mouse model to study the role of these mutations on the local immune microenvironment and in early endometriosis development. The outlined proposal will not only improve our understanding about the pathogenesis of endometriosis, but it will also generate potential new diagnostic methods and lead to novel personalized treatment options. Moreover, successfully managing this project will provide me with the additional scientific and translational skills necessary for moving up the career ladder towards a position as assistant professor in academia or senior scientist in industry.