O-GlcNAc transferase-dependent regulation of RNA Pol II activity in lethal prostate cancer

O-GlcNAc transferase (OGT), a cellular metabolic sensor and responder, is overexpressed in aggressive prostate cancer. We have developed small molecule inhibitors targeting OGT, and these compounds decrease the metabolic activity of prostate cancer cells. According to our research, OGT regulates global gene expression, albeit the mechanistic basis for this is not understood. Recently, we screened thousands of compounds to identify those that sensitize prostate cancer cells to OGT inhibition and identified a promising combination therapy against lethal prostate cancer. In this project, we will: 1) explain the molecular basis on how OGT regulates global gene expression and 2) further develop the promising anti-prostate cancer therapy. In brief, this project will describe a mechanism on how OGT integrates metabolic information to regulate global gene expression in normal and cancer cells, and we also aim to establish novel therapy for prostate cancer.