Qianben Wang Lab
General Research Interest
Nuclear receptor signaling in cancer
My laboratory is primarily interested in understanding the role of androgen receptor (AR) in the development and progression of prostate cancer. AR is a ligand-dependent transcription factor belonging to the nuclear hormone receptor (NR) superfamily. The application of chromatin immunoprecipitation (ChIP) to study protein-DNA interactions has provided a wealth of information on temporal and spatial assembly of AR transcription complexes on target gene regulatory regions in vivo. However, studying only a few target genes by ChIP greatly limits our understanding of how AR regulates vast target gene networks related to disease.
Recently, we have utilized high-throughput techniques such as ChIP-on-chip (ChIP on a microarray) or ChIP-seq (ChIP combined with high-throughput sequencing) to globally identify AR-bound genomic sites leading to target gene expression at various stages of prostate cancer, including androgen-dependent prostate cancer (ADPC) and castration-resistant prostate cancer (CRPC). By combining the AR binding maps with gene expression profiles, we have begun to understand how AR regulates target gene networks in ADPC and CRPC.
We are extending our view from transcriptional regulation by AR alone to include a wider view of transcription regulation in prostate cancer. These efforts have included studies of combinatorial transcriptional regulation by AR, its collaborating transcription factors (specifically the pioneer factors GATA2 and FoxA1), and its coactivators (namely the Mediator coregulatory complex subunit MED1). Additionally, we are applying similar approaches to reveal other important transcription factors that play roles in defining gene expression profiles that drive either ADPC or CRPC. These efforts are leading to many exciting results that result in more effective options for targeting AR activity throughout all stages of prostate cancer. Our results have indicated that several additional, and perhaps druggable, factors play an AR-independent role in supporting prostate cancer growth at various stages of the disease.
Most recently, we have begun to apply genome-wide ChIP techniques to clinical samples obtained from normal prostates and from different stages of prostate cancer. This has allowed us to identify critical AR-DNA interactions throughout prostate cancer genomes that contribute to disease progression through the gene-expression events they regulate.
Finally, our understanding of AR activity has allowed us to extend our investigations to look at NR signaling in non-prostatic cancers, such as breast and lung cancers.
888 Biomedical Research Tower
460 W 12th Avenue
Columbus, OH 43210
860A Biomedical Research Tower
460 W. 12th Avenue
Columbus, OH 43210
Dayong Wu, PhD – postdoctoral researcher
Zhong Chen, MD – research scientist
Cassandra Grenade, MD – postdoctoral fellow
Benjamin Sunkel, BS – graduate research fellowRussell Bonneville – student research assistant