Endometriosis is a benign gynecologic condition where the cells that normally line the uterus begin to grow outside of the uterus, usually on the ovary. Women with endometriosis frequently have pain and unexplained infertility. However, in a few women, the endometriotic cells may also develop into a specific kind of ovarian cancer, called endometrioid or clear cell ovarian cancer. Why endometriosis progresses to ovarian cancer is unknown. Additionally, women with endometriosis-associated ovarian cancers have a better prognosis than women without endometriosis. Recently, scientists have discovered a gene called ARID1A that may play a part in the transformation of benign endometriotic cells to malignant ovarian cancer cells. Our studies have shown that women with endometriosis-associated ovarian cancer have significantly lower levels of ARID1A. ARID1A binds to DNA and prevents cells from dividing too much, but in women who have a mutation in ARID1A, the dividing goes unchecked, allowing the formation of tumors. How ARID1A plays a role specifically in the formation of tumors is still unknown. Work in Dr. Hawkins’ lab will use human tissue samples from both benign and malignant ovarian diseases to study mutations in ARID1A in collaboration with mutations in other cancer causing genes. Work in culture will decipher the way ARID1A leads to increased proliferation through interactions with other genes. Using mouse models, Dr. Hawkins will also mimic the low levels of ARID1A as a way of measuring early tumor formation and the effects of potential therapies. This research will hopefully result in new, individualized methods of treating ovarian cancer and allow doctors to test patients with endometriosis before it progresses further.
This grant was made possible in part by a generous donation from the estate of Agatha Fort.
Shannon Hawkins, M.D., Ph.D., is an Assistant Professor in Obstetrics & Gynecology at Baylor College of Medicine. After receiving her B.S. from Ball State University in Indiana, she went on to obtain her Ph.D. in the Department of Biochemistry and Molecular Biology at Indiana University. After completion of her medical school training at Indiana University, she began an obstetrics and gynecology residency at Baylor College of Medicine (2002-2006), where she was an academic chief resident. During her residency, she was mentored by Dr. Matthew Anderson and studied the role of COUP-TFII in ovarian cancer. For this work, she was awarded the Pritchard Prize for Resident Research from the Texas Association of Obstetrics and Gynecology.
As junior faculty at Baylor College of Medicine, Dr. Hawkins became an ASRM-NICHD scholar of the Reproductive Scientist Development Program in 2006 where she worked under the mentorship of Dr. Martin M. Matzuk. This research project was awarded the NIH Loan Repayment Award for Contraception and Infertility Research. As a young physician-scientist, Dr. Hawkins was also a scholar of Baylor College of Medicine’s Women’s Reproductive Health Research Development Program. She is board certified in obstetrics and gynecology and maintains a general Ob/Gyn practice within the Harris County Hospital District where she trains many residents. Her laboratory focuses on the study of genomic variants in women with endometriosis, the role of microRNAs in the mouse and human uterus, and the progression of endometriosis to invasive ovarian cancer. Her Liz Tilberis Award will focus on the role of ARID1A in the transformation of endometriosis to ovarian cancer using human tissues, in vitro culture systems, and mouse models.