Endometriosis Project
Endometriosis is a chronic, pelvic inflammatory disease characterized by endometrial tissue growing in locations outside of the uterus. It effects approximately 10% of women and causes infertility and severe pain in many cases. Endometriosis has been shown to be heavily estrogen dependent. Aromatase, a key enzyme in the biosynthesis of estrogen, is abnormally expressed in endometriotic tissue and contributes to the proliferation of excess estrogen in this disease. Due to the importance of this enzyme in hormone dependent breast cancer, there are three FDA approved aromatase inhibitors already available (exemestane, anastrozole, and letrozole), but these have been linked to severe negative side effects, such as skin conditions and depression. Furthermore, they were all designed prior to elucidation of the aromatase structure. Recently, isoflavanones, a class of natural products, has been proposed to competitively bind to aromatase by mimicking the structure of the natural substrate, androstenedione (ASD). The goal of this project is to design a novel isoflavanone derivative using structure-guided design that competitively binds to aromatase as well as or better than the current FDA approved drugs. We utilize molecular docking software to screen potential inhibitors, and molecular dynamics (MD) simulations to model the movement and interactions of atoms in the system as a function of time.
Current Members:
Sarah Holmes, Georgia Hollingsworth, Maddie Bromfman
Past Members:
Abby Held, Ally Esselman, Molly Huebner, Madi Walker, Brock Boysan, Grant Freitas, Marissa Piña, and Yawa Kugbe