Sang Jun Han, Ph.D.

Among women’s reproductive disease, my lab has studies to figure out the molecular etiology of endometriosis and endometriosis-associated diseases. To achieve our scientific goal, my lab has three projects as follows:

Project 1: To Dissect Novel Molecular Pathogenesis of Endometriosis and Develops Small Molecular Inhibitors for Alternative Endometriosis Treatment: Endometriosis has been known as an estrogen-dependent inflammatory disease because estrogen signaling has an essential role in the pathogenesis of endometriosis. Therefore, previous endometriosis treatments systematically blocked estrogen signaling in endometriosis patients. However, this type of estrogen deficiency therapy has harmful side effects in other estrogen target tissues such as bone and brain, and administering such therapy to young women during their reproductive years can decrease bone production and depress mood. My strong interest in endometriosis led to my becoming the first to identify the new SRC-1 isoform that is required for endometriosis progression, which resulted in a publication (Han et al., Nature Medicine 2012). This finding is being further developed to find out how the SRC-1 isoform integrates estrogen signaling with the inflammatory response in ectopic lesions and how it cooperates with ERβ to promote ectopic lesion growth. Therefore, our novel ERβ/SRC-1 complex module will have profound impacts on current endometriosis paradigms and on alternative endometriosis treatments without the side effects of estrogen deficiency therapy.

Project 2: To Discover Main Causing Factors Induce Endometriosis-Associated Infertility: The disease afflicts 10%-15% of menstruating women causing debilitating pain and infertility. Endometriosis appears to affect every part of a woman's reproductive system including ovarian function, oocyte quality, embryo development and implantation, uterine function and the endocrine system choreographing the reproductive process and results in infertility or spontaneous pregnancy loss. Identifying and understanding the cellular and molecular mechanisms responsible for endometriosis-associated infertility might help unravel the confounding multiplicities of infertility and provide insights into novel therapeutic approaches and potentially curative treatments for endometriosis.

Project 3: Identification of Key Drivers of Tumorigenesis in Endometriotic Tissues: Endometriosis is classically defined as the presence of endometrial glands and stroma outside of the endometrial lining and uterine musculature. With an estimated frequency of 5%-10% among women of reproductive age, endometriosis is a common gynecologic disorder. While in itself a benign lesion, endometriosis shares several characteristics with invasive cancer, has been shown to undergo malignant transformation, and has been associated with an increased risk of epithelial ovarian carcinoma (EOC). Numerous epidemiologic studies have shown an increased risk of EOC among women with endometriosis. This is particularly true for women with endometrioid and clear cell ovarian carcinoma. However, the carcinogenic pathways by which endometriosis associated ovarian carcinoma (EAOC) develops remain poorly understood. Current molecular studies have sought to link endometriosis with EAOC through pathways related to oxidative stress, inflammation and hyperestrogenism. In addition, numerous studies have sought to identify an intermediary lesion between endometriosis and EAOC that may allow for the identification of endometriosis at greatest risk for malignant transformation or for the prevention of malignant transformation of this common gynecologic disorder. The objective of the current article is to review the current data regarding the molecular events associated with EAOC development from endometriosis, with a primary focus on malignancies of the endometrioid and clear cell histologic sub-types.