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

Project description

Cancer-associated mutations in endometriosis

Endometriosis is a chronic inflammatory condition affecting over 10 % of reproductive-age women. Endometriosis is characterised by the presence of endometrium-like tissue outside the uterus. Emerging evidence indicates the presence of cancer driver mutations in both the uterine and ectopic endometrium of patients. Although these mutations are known to modulate immune responses in cancer, their role in endometriosis remains unexplored. With the support of the Marie Skłodowska-Curie Actions programme, the MERMAID project will examine how these mutations influence the local immune microenvironment in the uterus and contribute to disease development. The research team aims to uncover novel mechanisms driving endometriosis and contribute to the design of personalised diagnostics and therapies.

Objective

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.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

STICHTING RADBOUD UNIVERSITAIR MEDISCH CENTRUM
Net EU contribution
€ 232 916,16
Address
GEERT GROOTEPLEIN 10 ZUID
6525 GA Nijmegen
Netherlands
Region
Oost-Nederland Gelderland Arnhem/Nijmegen
Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data