In the Chandler Lab, we are studying the integrated roles of cell signaling pathways and epigenetics in gynecologic diseases and cancer. |
In non-pregnant female mammals of reproductive age, ovulation (the releasing of eggs from the ovaries) and menstruation (the shedding of the uterine lining) occurs each month. This repeated cellular turnover can cause stress and inflammation, which puts females at risk for developing certain reproductive-tract diseases and cancer.
The goal of our research is to discover which genes and signaling pathways play a critical role in determining cellular homeostasis in the female reproductive system. We are particularly interested in understanding the epigenetic mechanisms that properly maintain endometrial epithelial cell identity and homeostasis in response to physiological stresses, such as obesity and metabolic disease, hypoxic stress or abnormal hormone levels. Our ultimate goal is to provide the discovery framework and rationale for the implementation of new or improved prevention strategies and drug therapies. Projects Our current research focuses on ARID1A (a subunit that facilitates SWI/SNF nucleosomal target substrate recognition), and its interaction with other proteins and signaling pathways in the female reproductive system. ARID1A is mutated in endometriosis, endometriosis-associated ovarian cancer, and endometrial cancer, as well as breast, gastric, bladder and pancreatic cancers. Other genes of interest include: CHD4 (a SWI/SNF-like remodeler), BAF180 (an alternative SWI/SNF subunit), P53 (a tumor suppressor), ARID1B and ARID2 (alternative SWI/SNF ARID subunits), BRG1 (SWI/SNF catalytic subunit), P300 (a histone acetyltransferase), P400 (a histone exchanger), PIK3R1 (a PI3-kinase regulator) and PTEN (a phosphatase in the PI3-kinase pathway which helps to prevent uncontrolled cell growth that can lead to tumors). Projects include preclinical drug studies, chromatin-based mechanisms of disease prevention, epigenetic regulation of hormone signaling and the contributions pathophysiological or environmental risk factors to endometrial pathologies. In vivo genetically engineered mouse models (GEMM) of gynecologic disease and cancers. Genomic studies to explore genome-wide chromatin remodeling function in the female reproductive tract. |