Research Projects

Breast cancer is the most common cancer in women and the second most common cancer overall. Despite successful first line therapies, a significant percentage of women develop resistance to standard endocrine therapies or their disease recurs. Understanding why some women relapse or develop resistance is crucial for identifying new therapeutic targets for relapsed disease. A gene identified in a genotype to phenotype screen associated with poor survival outcomes when highly expressed was Jumonji domain containing 6 (JMJD6). JMJD6 modifies many proteins important in cancer, including demethylation of arginine residues on histones, estrogen receptor (ER), hydroxylation of H3K5 and p53, and phosphorylation of H2A.X to promote autophagy in breast cancer. JMJD6 is an epigenetic modifier of gene expression, indirectly binding to the promoter of lincRNA HOTAIR, which is associated with metastatic death. It also bound regulatory regions of several cell cycle genes and was regulated by EZH2. To study Y-box interacting protein 1 (YBX1), researchers performed mass spectrometric analysis of proteins immunoprecipitated using JMJD6-specific antibodies. YBX1 has both RNA and DNA binding activity, and its high expression is associated with poor prognosis, increased cell proliferation, and cell motility. This proposal explores the physical binding of JMJD6 and YBX1 and their potential co-binding at regulatory regions of their transcriptional targets. The data will provide the basic mechanistic underpinnings of their joint interactions in gene regulation and determine if they worsen patient survival when co-expressed together.