My laboratory is focused on the transcriptional regulation of estrogen receptor (ER) signaling pathways by nuclear receptor co-factors. Estrogen receptors regulate cell proliferation, differentiation and cell cycle control in a cell- and tissue-specific manner. The effect of estrogen in etiology and progression of breast cancer is ascribed to ER-promoted cell proliferation. We have discovered that some ER co-regulatory proteins regulate ER-mediated growth inhibition rather than proliferation. We are in the process of exploring the molecular mechanisms by which nuclear receptor coactivators regulate ER-mediated growth inhibition and attempting to develop novel chemotherapy strategies to treat ER-positive breast cancer. Furthermore, we aim to understand the crosstalk between ER pathways and other growth factors and kinase networks, as these mechanisms account for the intrinsic or acquired tamoxifen resistance in endocrine therapy.
An important epigenetic route to carcinogenesis involves the aberrant patterns of histone modifications in chromatin, leading to alterations in gene expression and transformation from normal to cancer cells. The second focus of our lab is to explore the functional roles of histone arginine methylation in the epigenetic control of cancer cells. Our major interest is on a protein arginine methyltransferase CARM1/PRMT4, a nuclear hormone receptor co-activator. Histone H3 methylation by CARM1 potentiates target gene activation by ER. Our ongoing studies include combining biochemical and functional genomic approaches to understand the role and regulation of histone R methylation in the transcriptional control of ER. In addition to learning about how CARM1 regulates ER in cancer cells, we will employ mice genetics to decipher the significance of histone arginine methylation in tumor prevention, thereby facilitating the rational design of novel chemotherapy drugs by targeting the epigenome in breast cancer.
- Joined ERP Program: 2010
- PI DOD ERA of HOPE Award 4/1/2011- 3/31/2016 Old receptors, new treatment strategies for breast cancer
- University of Wisconsin Graduate School Villas Life Cycle Professorship, 7/1/2014-6/30/2015
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