Junjie Feng

About Junjie Feng

Systematic identification of genetic variants within AR binding sites that are associated with altered AR signaling and prostate cancer

Androgen Receptor (AR) mediates the action of the male hormones, androgens by binding to genomic DNA and regulating gene expression. This AR-mediated cellular signaling is dysregulated in prostate cancer. As the cancer progresses towards treatment resistance, AR becomes independent of the presence/absence of androgens and upregulates pro-cancer gene expression. The precise sites on the genome to which AR binds are called AR Response Elements (AREs) or AR binding sites. Recent reports have shown that approximately 1/3 of all known prostate cancer risk-associated genetic variants reside in these AR binding sites. Genetic variations that predispose a man to prostate cancer are usually found to be concentrated in the specific DNA regions to which AR binds.

Other PCF-funded studies have shown that AR signaling is causally related to the formation and/or expression of recurrent oncogenic gene fusions (e.g. TMPRSS2-ERG), suggesting that altered AR signaling caused by inherited genetic changes may have a profound impact on the pathogenesis and progression of prostate cancer. To test this hypothesis, Dr. Junjie Feng proposes to 1) identify genome-wide AR binding sites and prostate cancer-specific fusion genes; 2) prostate cancer risk/aggressiveness-associated genetic variants that are located within AR binding sites, and 3) assess whether these genetic variants cause altered AR signaling and influence the formation and/or expression of fusion genes.

Dr. Feng’s research will deepen our understanding of the pivotal role of the androgen-AR signaling axis in the pathogenesis and progression of prostate cancer. These results will also impact the clinical management of the disease by efficient patient stratification based on their specific underlying genetic predispositions. The genetic variants identified in this study also have the potential to serve as valuable biomarkers for accurate prostate cancer screening and diagnosis.