Housheng Hansen He

At a Glance

• Cancer Genetics and Epigenetics
• Noncoding RNA, RNA Therapy
• Data Science and Computational Biology

Research Synopsis

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. 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 RNAs, particularly long non-coding RNA (lncRNA) and circular RNA (circRNA), have 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.

Our laboratory applies a variety of genomic, epigenomic experimental and computational approaches to elucidate the functional role of epigenetic regulation in cancer development, progression, drug response and resistance, with a special focus on the interplay between epigenetic regulator and noncoding RNA under stress conditions such as hypoxia. Our research focuses on three major directions. 

1. Understand epigenetic regulation in cancer development, progression, drug response and resistance
2. Identify epigenetic biomarkers in tumor and liquid biopsies.
3. Target cancer specific epigenetic regulation for cancer therapy, in particular RNA therapy.

Recent Publications

1. Wang S*, Gao S*, Zeng Y*, Zhu L, Wong C, Su P, Zhai J, Soares F, Xu X, Yang Z, Cheung H, Chen H, O’Brian C, Rottapel R, Kang W, Cai Z, Wu J, Yu J#, He H#. N6-methyladenosine reader YTHDF1 promoted colorectal tumorigenesis and metastasis through ARHGEF2. Gastroenterology. 2022. PMID: 34968454.
2. Ahmed M*, Soares F*, Xia J-H*, Yang Y, Li J, Guo H, Su P, Tian Y, Lee H, Wang M, Akhtar N, Houlahan K, Bosch A, Zhou S, Mazrooei P, Hua J, Chen S, Petricca J, Zeng Y, Fraser M, Quigley D, Feng F, Boutros P, Lupien M, Wang L, Walsh M, Wang T, Ren S#, Wei G-H#, He H#. CRISPRi screens reveal a DNA methylation-mediated 3D genome dependent causal mechanism at the 8q24 prostate cancer risk locus. Nature Communications. 2021. PMID: 33741908.
3. Chen S*, Zhu G*, Yang Y*, Wang F*, Xiao Y, Zhang N, Bian X, Zhu Y, Yu Y, Liu F, Dong K, Mariscal J, Liu Y, Soares F, Yau H, Zhang B, Chen W, Wang C, Chen D, Guo Q, Yi Z, Liu M, Fraser M, De Carvalho D, Boutros P, Vizio D, Jiang Z, Kwast T, Berlin A, Wu S, Wang J#, He H#, Ren S#. Single-cell analysis reveals transcriptomic remodellings in distinct cell types that contribute to human prostate cancer progression. Nature Cell Biology. 2021. PMID: 33420488.
4. Soares F*, Chen B*, Lee JB, Ahmed M, Ly D, Kang H, Schimmer A, Minden M, He H#, Li Z#. CRISPR/Cas9 screen identifies genes that sensitize double negative T cell Therapy in leukemia. Blood. 2021. PMID: 33270841.
5. Gao S*, Chen S*, Han D, Zhou F, Barrett D, Luong MP, Han W, Avery AM, Petricca J, Yuan M, Asara JM, Macoska JA, Balk SP#, He H#, Cai C#. Chromatin binding of FOXA1 is promoted by LSD1-mediated demethylation in prostate cancer. Nature Genetics. 2020. PMID: 32868907.
6. Chen S*, Huang V*, Xu Xin*, Julie L*, Soares F*, Jeon J, Zeng Y, Hua J, Petricca J, Guo H, Wang M, Yousif F, Zhang Y, Donmez N, Ahmed M, Volik S, Lapuk A, Chua M, Heisler L, Foucal A, Fox N, Fraser M, Bhandari V, Shiah Y, Guan J, Orian M, Picar V, Hovington H, Bergeron A, Lacombe L, Fradet Y, Tetu B, Liu S, Feng F, Wu X, Y Shao, Komor M, Sahinalp C, Collins C, Hoogstrate Y, Jong M, Fijneman R, Fei T, Jenster G, van der Kwat T, Bristow RG, Boutros P#, He H#. Widespread and functional RNA circularization in localized prostate cancer. Cell. 2019. PMID: 30735634.
7. Gao S*, Chen S*, Han D, Barrett D, Han W, Ahmed M, Patalano S, Macoska J, He H#, Cai C#. Forkhead domain mutations in FOXA1 drive prostate cancer progression. Cell Research. 2019. PMID: 31324883. 
8. Hua J, Ahmed M, Guo H, Zhang Y, Chen S, Soares F, Lu J, Zhou S, Wang M, Li H, Larson N, McDonnell S, Patel P, Liang Y, Yao CQ, Kwast T, Lupien M, Feng F, Zoubeidi A, Tsao M, Thibodeau SN, Boutros P, He H. Risk SNP-Mediated Promoter-Enhancer Switching Drives Prostate Cancer through lncRNA PCAT19. Cell. 2018. PMID: 30033362. 
9. Liu Y, Chen SJ, Wang S, Fischer M, Decaprio JA, Meyer C, Brown M#, Liu X#, He H#. Transcriptional Landscape of the Breast Cancer Cell Cycle. PNAS. 2017. PMID: 28289232. 
10. Guo H, A.M., Liang Y, Hua J, Langstein J, Poon C, Bailey S, Desai K, Fei T, Li Q, PrensnerJR, Pomerantz M, Feng FY, Freedman M, Lupien M, He H. Modulation of long noncoding RNAs underlying genetic predispositions to prostate cancer. Nature Genetics. 2016. PMID: 27526323.

Graduate Students

Vivian Chu
Peter Her
Peiran Su
Mona Teng
Lin Yang
Helen Zhu