My laboratory is primarily interested in understanding the epigenetic mechanisms driving progression of hormone-dependent cancers. One key area of our research is studying the genomic function of androgen receptor (AR) in prostate cancer. AR is a ligand-dependent transcription factor belonging to the nuclear hormone receptor (NR) superfamily. Recently, we have utilized high-throughput techniques such as ChIP-exo (chromatin immunoprecipitation-exonuclease combined with high-throughput sequencing) and ChIP-seq (ChIP combined with high-throughput sequencing) to globally identify AR-bound genomic sites and precisely define AR binding motifs leading to target gene expression, cancer progression and treatment resistance.
We are expanding our focus from transcriptional regulation by AR alone to include a wider view of global transcriptional regulation in prostate cancer. These efforts have included studies of transcription factor-centered, multi-layer transcription regulatory networks in prostate cancer, which involve transcription factors (e.g. AR, FOXA1, GATA2 and CREB1), transcription coactivators (e.g. Mediator and histone acetyltransferases), and epigenetic regulators (e.g. histone modifications, chromatin looping and nucleosome positioning). These efforts are leading to many exciting results that will inform the development of more effective options for prostate cancer, as existing treatments predominantly target AR itself.
Finally, our understanding of AR genomic activity has allowed us to extend our investigations to study the genomic functions of other NRs (e.g. glucocorticoid receptor [GR] and estrogen receptor [ER]) in other hormone-dependent cancers, such as breast cancer.