Date of Award

Spring 2026

Abstract

Endometriosis is a benign gynecological disease that affects roughly 10% of women and peoplewith a uterus worldwide. Endometriosis is associated with aberrant activation of the protein signal transducer and activator of transcription 3 (STAT3) which regulates multiple cellular processes. We sought to understand the role STAT3 plays in the development of endometriosis. First, in chapter 2, we evaluated the ability of endometriosis cells to form spheroids and if they could undergo the process of mesothelial clearance. We demonstrated that 12Z endometriosis cell spheroids and hEM3 endometrial cell spheroids could clear a monolayer of mesothelial cells and that lovastatin, a drug used to treat high cholesterol, reduced this ability. Additionally, we found that 12Z cell spheroids resulted in a consistently larger clearance ratio than the normal endometrial hEM3 cell spheroids. Next, in chapter 3, we assessed the role of STAT3 and specific STAT3 target genes in endometriosis. We determined that 12Z endometriosis cells were more sensitive to STAT3 inhibition than the normal hEM3 endometrial cells, however STAT3 inhibition did not consistently or significantly reduce the clearance ratio of 12Z and hEM3 cell spheroids. Lastly, in chapter 4, we assessed STAT3 in relation to the iron-dependent cell death process of ferroptosis. We observed that STAT3 inhibition had opposite effects on ferroptosis preventing genes in 12Z endometriosis and hEM3 endometrial cells. We also discovered that RSL3, a ferroptosis promoting drug, significantly decreases STAT3 expression and mesothelial clearance. These studies emphasize the multifaceted role of STAT3 and the important differences in regulation it has in endometriosis.

Document Type

Dissertation

First Advisor

Sarah R Walker

Second Advisor

Paul C Tsang

Third Advisor

Sherine Elsawa

Department or Program

Biochemistry

Degree Name

Doctor of Philosophy

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