Monthly Publication Highlight - Dr. Chang-Deng Hu
October 2016 - The Purdue College of Pharmacy is pleased to honor and recognize the outstanding research and scholarship generated by our faculty each month. This month we highlight Dr. Chang-Deng Hu, Professor of Medicinal Chemistry and Molecular Pharmacology.
Dr. Hu’s recent publication, "Protein arginine methyltransferase 5 functions as an epigenetic activator of the androgen receptor to promote prostate cancer cell growth”, can be read in Oncogene (August 22, 2016; doi: 10.1038/onc.2016.287). The work was completed by research assistant Xuehong Deng and two visiting scholars, Dr. Huantian Zhang and Dr. Genbao Shao, as well as other collaborators Drs. Chenglong Li, Dabao Zhang, Bennet Elzey, Roberto Pili, Timothy Ratliff, and Jiaoti Huang at Purdue University, UCLA, The Ohio State University, and Indiana University. The work performed at the Purdue College of Pharmacy was completed in the RHPH 225 laboratory.
Protein arginine methyltransferase 5 (PRMT5) is an emerging epigenetic enzyme that regulates gene expression. In collaboration with Dr. Jiaoti Huang at UCLA and Dr. Liang Cheng at Indiana University School of Medicine, they found that PRMT5 is overexpressed in prostate cancer tissues. Interestingly, PRMT5 expression level correlates positively with the expression of androgen receptor (AR) in these tissues. Using a genetic knockdown approach and a novel PRMT5 inhibitor BLL3.3 developed by collaborator Dr. Chenglong Li at The Ohio State University, they found that PRMT5 expression is required for prostate cancer cell growth in vitro and xenograft tumor growth in mice in an AR-dependent manner. Contrary to the primary role of PRMT5 in repressing gene expression in cancer cells, their mechanistic study revealed that PRMT5 epigenetically activates expression of AR in prostate cancer cells. These findings suggest that PRMT5 may promote prostate cancer development and progression by activating the expression of AR.
“We are very excited about this novel finding because AR not only drives prostate cancer development and progression, but also is the validated therapeutic target of current androgen deprivation therapy, also known as hormone therapy for metastatic prostate cancer,” comments Dr. Hu. “The problem with hormone therapy is that almost all patients become resistant to the treatment within 2-3 years by overexpressing AR, AR mutations, or other mechanisms that lead to AR activation. We hope targeting PRMT5 will provide a novel way to treat prostate cancer by eliminating AR expression.”