Role of the gut microbiota in endometriosis - 7R01HD102680 (2021-2026)
A five-year grant funding from HIH NICHD. The aims of the project are to:
- Determine the mechanism by which gut bacteria promote endometriosis
- Determine the mechanism by which gut microbiota-derived short-chain fatty acids (SCFAs) affect endometriosis
- Identify human gut bacteria associated with endometriosis and determine the effect of gut bacteria on growth of human endometriotic tissue in mice.
The aims are based on our observations that feces from mice with endometriosis contain less of the microbiota-derived (SCFA) n-butyrate than feces from mice without endometriosis. Furthermore, treatment with n-butyrate reduces growth of both mouse- and human-endometriotic lesions in the mouse model. At the level of basic science, this project will identify gut bacteria and inflammatory profiles that confer sensitivity to developing endometriosis and identify mechanisms by which SCFAs protect against endometriosis. Of long-term translational significance, this work could lead to development of dietary recommendations, supplements, or probiotics to prevent endometriosis in reproductive-age women.
Role of SF3B1 in endometrial cancer – (ACS June 2021-June 2024)
A four-year grant from the “American Cancer Society” to identify the mRNA splicing alterations caused by overexpression or increased activity of splicing factors that promote endometrial cancer progression. For this aim, we are generating uterine-specific knockout mice models of splicing factors to assess their role in estrogen-driven endometrial hyperplasia in vivo. Results from this project may lead to exploration of progesterone-induced alternative splicing in other endocrine-regulated tissues and may also lead to exploring estrogen-induced alternative splicing in other cancers.