General Research InterestNuclear receptor signaling in prostate and breast cancer
Research DescriptionMy laboratory is 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 interaction has provided a wealth of information on temporal and spatial assembly of AR transcription complex on target gene regulatory regions in vivo. However, studying of only a few target genes by ChIP greatly limits our understanding of how AR regulates target gene network. The recent development of the ChIP-on-chip (ChIP on a microarray) or ChIP-seq (ChIP combined with high throughput sequencing) technique allows the global identification of specific transcription factor regulatory regions across the human genome. Recently, we have mapped AR binding regions in the entire human genome in both androgen-dependent prostate cancer (ADPC) and androgen-independent prostate cancer (AIPC). By combining the AR binding maps with gene expression profiles, we have begun to understand how AR regulates target gene networks in ADPC and AIPC. Currently, we are extending our view from transcriptional regulation by AR to wider transcriptional regulations in prostate cancer including studying combinatorial transcriptional regulation by AR, its collaborating transcription factors, and its coactivators. We will also apply the genome-wide ChIP technique to clinical samples obtained from different stages of prostate cancer. This would allow identification of critical cis-regulatory sequences contributing to prostate cancer progression.
Transinstitutional WorkMy Bioinformatics collaborator is Dr. Wei Li ( Assistant Professor, Division of Biostatistics, Dan L. Duncan Cancer Center, Baylor College of Medicine) who is a leader in sequence and microarray data analysis. We are currently collaborate on a NCI funded R00 project “ Genome-wide analysis of transcription factor function in prostate cancer”.The overall goal of this project is to improve our understanding of the combinatorial transcriptional regulation of target genes by AR, its collaborating transcription factors and its coactivators from a genome-wide view in ADPC and AIPC