CXCR4 Regulation: Methylation Dynamics In Endometriosis

PROJECT SUMMARY Endometriosis is a chronic, underdiagnosed, and understudied disease characterized by the growth of endometrial-like tissue outside the uterus, causing pain, infertility, and significant quality of life impairment. However, despite its prevalence, the precise etiology of the disease remains unclear, resulting in a substantial delay in diagnosis and treatment. Current diagnostic methods are often invasive, and there is a lack of non- hormonal, effective treatments. This proposal aims to investigate the epigenetic regulation of “CXCR4”, a master regulator (a key molecular factor that links inflammation, migration, immune evasion, angiogenesis and stem cell trafficking), that is involved in the pathogenesis of endometriosis. Studies from our laboratory, and others have shown CXCR4 to be involved in migration of endometrial cells and stem cell trafficking leading to lesion formation in endometriosis. However, factors leading to this functional aberration in CXCR4 are not currently known. By understanding CXCR4’s regulatory functions and impact on the disease, this translational research aims to identify CXCR4 promoter methylation as a novel biomarker for earlier diagnosis and non-hormonal therapeutic target for treatment. This study hypothesizes that aberrant promoter methylation dynamics of CXCR4 plays a key role in the etiology of endometriosis. Undergraduate students will learn to use cutting-edge techniques such as Methylation PCR arrays and Re-ChIP-qPCR to determine how this master regulator contributes to the aberrant cell behavior observed in endometriosis. The first objective will determine the changes in methylation status of the CXCR4 promoter based on human endometriotic lesion type and stage of endometriosis. The second objective will investigate the bivalency of the CXCR4 promoter, and the final objective will determine the antagonizing role of KDM6 on the epigenetic regulation of CXCR4 promoter. This study will provide research experience to STEM undergraduate students to perform clinical-translational research in a topic of high clinical and public health significance. The findings from this study will not only deepen our understanding of endometriosis but also offer new avenues for developing targeted, non-hormonal therapies, ultimately improving both the diagnosis and management of this debilitating condition.