The Kim Laboratory is interested in elucidating mechanisms of progesterone receptor (PR) action in uterine tissues. Specifically PR function is studied in different uterine diseases: Endometrial Cancer, Endometriosis and Uterine Fibroids.
Endometrial cancer is the most common gynecologic cancer diagnosed in the United States with an estimated 40,00 new cases resulting in approximately 7,500 deaths. As risk factors for endometrial cancer increase, the incidence of endometrial cancer will also rise, with a paradigm shift to younger ages. In our laboratory, we investigate the role of progesterone receptor in endometrial cancer to understand why progestin therapy is not an effective treatment in all cases of endometrial cancer. We are also looking at specific signaling pathways that control progesterone receptor function as potential targets of therapy.
|NIH R01 CA155513: Influence of AKT pathway on progesterone receptor function in endometrial cancer|
Endometriosis is an estrogen-dependent disorder affecting up to 10% of the female population and 30-50% of infertile women, with no cure and limited therapies. It is often associated with debilitating pelvic pain and infertility. This disease has also been referred to as a “progesterone resistant” disease since the ectopic and eutopic tissues do not respond to progesterone as it does in normal endometrial tissues. Our laboratory is investigating progesterone resistance in endometriosis and identifying specific biological targets for the future development of alternative therapies.
|NIH R01 HD044715: Mechanism of Progesterone Receptor Action in Endometriosis, Friends of Prentice|
Leiomyoma (Uterine Fibroids)
Uterine fibroids, also known as leiomyomas, are benign tumors originating from the myometrium. These tumors can range from a few millimeters to over 20 cm in size. Leiomyomas are common and can occur in up to 77% of women while up to 20% of women suffer from significant morbidity, pain and discomfort, and excessive menstrual bleeding. Leiomyomas are the primary indication for over 200,000 hysterectomies in the United States. In our laboratory we are investigating how progesterone promotes growth of leiomyomas by focusing on the non-genomic signaling of progesterone on the PI3K/AKT pathway. These studies are translated to the identification of important signaling molecules that can be targeted using small molecule inhibitors.
|NIH P01 HD057877: Molecular and functional crosstalk of progesterone receptor and the PI3K/AKT/FOXO pathway in uterine leiomyoma|
Uterus- Building a microphysiological system
The primary goal of this study is to build a human reproductive tract, including the ovary, fallopian tube, uterus, cervix and vagina into a microphysological system that will enable in vitro testing of hormones, drugs and toxic compounds. The Kim Lab is focusing on building three dimensional cocultures of uterine cells which will respond to exogenous estrogen and progesterone.
|UH2-NIH: Microphysiologic Systems|
The endocervix is a hormonally responsive tissue that secretes cervical mucus and other proteins in response to hormones during the menstrual cycle. In collaboration with investigators stuyding HIV transmission (Thomas Hope, Northwestern), this project focuses on identification of hormonally regulated genes that are involved in influencing HIV transmision in the female reproductive tract.
|Gates Foundation: Gene regulation in the Cervix during the menstrual cycle|
Epidemologic and laboratory studies strongly point to a pro-proliferative role of progesterone in the breast. In collaboration with Dr. Seema Khan (Northwestern), this study explores the potential use of selective progesterone receptor modulators for the prevention of breast cancer in high risk women.
|Lynn Sage Foundation: Progesterone antagonists for the prevention of breast cancer.|