Housheng Hansen He
Associate ProfessorPh.D., Institute of Biophysics, Chinese Academy of Sciences, Beijing
Toronto Medical Discovery Tower
101 College Street, Room 11-305
Toronto, Ontario M5G 1L7
Lab Phone: 416-634-8763
Email Dr. Housheng Hansen He
Noncoding RNA and epigenetic regulation in cancer development, progression and drug response
Cancer arises from breakdown in the normal cellular regulatory system. This malfunction can be a consequence of genetic mutation as well as epigenetic changes. Key epigenetic alterations, including histone modification and DNA methylation, often result in global as well as localized chromatin packaging that influences the transcription of genes important to cancer. While genetic changes are almost impossible to reverse, epigenetic alterations are potentially reversible. Drugs that modify the epigenetic state promise to be effective new cancer therapies. However, the mechanism(s) underlying the epigenetic regulation of cancer cells, as well as the way in which drugs manipulate the epigenetic state and transcription, remain largely unknown. Moreover, as epigenetic regulation is critical for maintaining normal cellular function, the characterization of cancer-specific epigenetic reprogramming is an essential step for increasing specificity of epigenetic therapy. Noncoding RNA, particularly long non-coding RNA (lncRNA), has recently become a new area of focus in cancer biology, with evidence suggesting that they are essential to epigenetic reprogramming during cancer development and progression.
The He laboratory applies a variety of genomic, epigenomic experimental and computational approaches to elucidate the functional role of epigenetic regulation in cancer development, progression and drug response, with a special focus on the interplay between epigenetic regulator and noncoding RNA. Combine the experimental and computational expertise, we are in a unique position to make major contributions to both the general understanding of cancer biology and the improvement of epigenetic therapy. Our research focuses on three major directions. 1. Role of noncoding RNA and epigenetic regulator in transcriptional regulation. 2. Molecular mechanism(s) of epigenetic regulation in cancer development, progression, drug response and resistance. 3. Development of experimental and computational approaches for genome-wide epigenetic and noncoding RNA analysis.
List of Key Publications:Link to Pubmed Publications
He H , Meyer CA, Chen MW, Zang CZ, Hu S, Liu Y, Liu XS, Brown M. Optimized DNase-seq for efficient transcription factor binding site and footprint identification. Nature Methods. 2013. Accepted in principle.
Sun T, Wang X, He H , Sweeney C.J, Liu X.S, Brown M, Lee G.M, Kantoff P.W. Targeting MED1, HECTD2 and RAB1A by mir-221/222 promotes the development of androgen independency of prostate cancer cells. Oncogene. 2013. PMID: 23770851.
Cai C, Wang H, He H , Chen S, Mucci L, Wang Q, Flore C, Sowalsky A, Loda M, Liu XS, Brown M, Balk S, Yuan X. ERG Activation of an Androgen Receptor Regulated Enhancer in the SOX9 Gene Mediates Tumor Development in TMPRSS2:ERG Fusion Positive Prostate Cancer. Journal of Clinical Investigation. 2013. PMID: 23426182.
He H , Meyer CA, Chen MW, Jordan VC, Brown M, Liu XS. Differential DNase I Hypersensitivity reveals Factor-dependent Chromatin Dynamics. Genome Research. 2012. PMID: 22508765.
Xu K, Wu Z, Groner A, He H , Cai C, Liu T, Thornton J, Gregory R, Loda M, Stack E, Kantoff P, Balk S, Liu X.S, Brown M. EZH2 Oncogenic Activity in Castration Resistant Prostate Cancer is Polycomb-Independent. Science. 2012. PMID: 23239736.
Cai C, He H , Chen S, Coleman I, Wang H, Fang Z, Nelson PS, Chen S, Brown M, Balk SP. Androgen receptor gene expression in prostate cancer is directly suppressed by the androgen receptor through recruitment of lysine-specific demethylase 1. Cancer Cell. 2011. PMID: 22014572.
Meyer CA, He H , Brown M, Liu XS. BINOCh: Binding Inference from Nucleosome Occupancy Changes. Bioinformatics. 2011. PMID: 21551136.
Verzi M, Shin H, He H , Sulahian R, Meyer C, Montgomery R, Fleet J, Brown M, Liu XS, Shivdasani R. Differentiation-specific histone modifications reveal dynamic chromatin interactions and alternative partners fo
He H , Meyer CA, Shin H, Bailey S, Wei G, Wang Q, Zhang Y, Xu K et al: Nucleosome Dynamics Define Transcriptional Enhancers. Nature Genetics. 2010. PMID: 20208536.
Li T, He H , Wang Y, Skogerbø G, Chen R. “In vivo analysis of Caenorhabditis elegans noncoding RNA promoter motifs”. BMC Molecular Biology. 2008. PMID: 18680611.
He H , Wang J, Liu T, Liu XS, Li T, Wang Y, Qian Z, Zheng H, Zhu X, Wu T, et al. “Mapping the C. elegans noncoding transcriptome with a whole-genome tiling microarray”. Genome Research. 2007. PMID: 17785534.
He H , Cai L, Skogerbø G, Deng W, Liu T, Zhu X, Wang Y, Jia D, Zhang Z, Tao Y, et al. “Profiling Caenorhabditis elegans non-coding RNA expression with a combined microarray”. Nucleic Acids Research. 2006. PMID: 16738136.