Sang Jun Han Lab
Project 1: Estrogen/Estrogen Receptor Beta axis in endometriosis
Endometriosis is an estrogen-dependent disease. Therefore, the estrogen/Estrogen Receptor (ER)s axis has a critical role in endometriosis progression. Among ERs, the ER-beta level is significantly elevated in endometriotic tissues as compared with normal endometriosis. Now, we will investigate the role of ER-beta in endometriosis progression with the OMICs data set.
Project 2: Dysregulation of Immune in endometriosis
Retrograde menstruation is the main driving factor to initiate the endometriosis progression. To shedding endometrial fragments is developed into endometriotic lesions, the immune system should be dysregulated compared to normal women. However, it is not elucidated how the immune system is changed in endometriosis patients to allow endometriotic lesions. Now, we investigate how endometriotic lesions dysregulate and then generate an endometriosis-competent immune environment to enhance endometriosis.
Project 3: Endocrine disruptor in endometriosis progression
The central hypothesis of endometriosis is retrograde menstruation. Most of the reproductive-aged women (90%) have experienced retrograde menstruation, but 10% of women suffer from endometriosis symptoms. In addition to retrograde menstruation, however, other factors should involve in the initiation of endometriosis. Our hypothesis is the exposure of the environment hormone causes endometriosis progression along with retrograde menstruation. Now, we will investigate the molecular etiology of environmental hormone in endometriosis initiation.
Project 4: Alteration of epigenetic regulation in endometriosis
In addition to genetic variation, the altered epigenomic pattern is also associated with the endometriosis progression. For example, the DNA methylation pattern is quite different between normal endometrium versus endometriotic tissues. Therefore, our project aims to define how DNA methyltransferase involves endometriosis progression with various animal models and human endometriotic lesions.
Project 5: Genetic Mutation Causing Endometriosis
Previous studies revealed exon specific gene mutations are defined in endometriosis patients. However, it is not clearly elucidated whether these genes mutation causes endometriosis progression. Using the CRISPR/Cas9 system, we will determine whether these gene mutations initiate and progress the endometriosis.
Project 6: Diet therapy for the endometriosis
Our studies revealed that ER-beta has an essential role in endometriosis progression. However, most ER beta antagonists also inhibit ER-alpha activity in vivo and then caus side effects by suppressing ER-alpha activity. To effectively suppress endometriosis without side effects, we have screened natural ligands that effectively inhibit ER-beta activity but not ER-alpha activity. Now, we will investigate whether foods that contain high levels of ER-beta inhibiting natural ligands suppress the endometriosis progression.
Cancer
Project: Adoptive Cell Therapy with Steroid Receptor Coactivator (SRC)-3 KO Tregs To Eradicate high mortality hormone-related cancers
Tregs are essential in restraining immune responses for immune homeostasis. SRC-3 is a pleiotropic coactivator, the second-most highly expressed transcriptional coactivator in Tregs, and a suspect in Treg function. Our study showed that the disruption of SRC-3 expression in Tregs leads to 'complete lifetime eradication' of tumors in aggressive syngeneic breast cancer mouse models because deletion of SRC-3 alters the expression of a wide range of key genes involved in efferent and afferent Treg signaling. SRC-3KO Tregs confer this long-lasting protection against cancer recurrence in mice without an apparent systemic autoimmune pathological phenotype. Therefore, our team will develop the SRC-3 deleted Tregs cell therapy as a novel and efficient future treatment for eliminating tumor growth and recurrence without the autoimmune side-effects that typically accompany immune checkpoint modulators.
