郑诗乐教授 – 生物醫學學院

郑诗乐教授

Professor

39439842

alfredcheng@cuhk.edu.hk

https://chenglabcuhk.com/

Rm 406A, Lo Kwee-Seong Integrated Biomedical Sciences Building, Area 39, CUHK

Publons

ORCID

个人简介

Prof. CHENG Sze Lok Alfred (郑诗乐) is a Professor in the School of Biomedical Sciences and Assistant Dean (Research) of the Faculty of Medicine at The Chinese University of Hong Kong (CUHK). He completed his Ph.D. under the supervision of Prof. Joseph Sung in the Department of Medicine and Therapeutics at CUHK in 2002 and went on his postdoctoral training in Ohio State University until 2007. Prof. Cheng has published in international journals including Molecular Cell, Nature Genetics, Journal of Clinical Investigation, Cancer Research, Gastroenterology, Gut, Journal of Hepatology, Nature Communications and Nucleic Acids Research. He has received >20 academic honors and awards, including recognitions from the American Association of Cancer Research (AACR) and United European Gastroenterology (UEG). He was a recipient of the Most Promising Young Investigator Award by Hong Kong Government (2014) and CUHK (2015). He has been recently awarded the Asa Briggs Visiting Fellowship in 2017 by the University of Sussex and the Visiting Professorship in 2018 by the Southwestern Medical University. Until 2019, he has presided as Principal Investigator (PI)/co-PI in ~30 local and national competitive grants with a sum of over 90 million HK dollars. His current research focuses on the epigenetic mechanisms in tumors and their microenvironment, aiming at the enhancement of cancer immunotherapy.

Research Interests

Epigenetic regulation of tumor cells and tumor microenvironment.
Transcriptional enhancers in carcinogenesis.
Molecular mechanisms underlying male predominance of liver cancer.

Selected Publications

Yang, W., Feng, Y., Zhou, J., Cheung, O.K., Cao, J.Q., Wang, J., Tang, W.S., Tu, Y.L., Xu, L.L., Wu, F., Tan, Z., Sun, H., Tian, Y., Wong, J., Lai, P.B., Chan, S.L., Chan, A.W., Tan, P., Chen, Z., Sung, J.J., Yip, K.Y.L., To, K.F., Cheng, A.S.* (2021). A selective HDAC8 inhibitor potentiates antitumor immunity and efficacy of immune checkpoint blockade in hepatocellular carcinoma. Science Translational Medicine, In press.
Zeng, X., Zhou, J., Xiong, Z., Sun, H., Yang, W., Mok, M., Wang, J., Li, J., Liu, M., Tang, W., Feng, Y., Wang, H.K.S., Tsang, S.W., Chow, K.L., Yeung, C., Wong, J., Lai, P.B.S., Chan, A.W.H., To, K.F., Chan, S.L., Xia, Q., Xue, J., Chen, X., Yu, J., Peng, S., Sung, J.J.Y., Kuang, M., Cheng, A.S.* (2020). Targeting Monocyte-intrinsic Enhancer Reprogramming Improves Immunotherapy Efficacy in Hepatocellular Carcinoma. Cellular & Molecular Immunology, doi: 10.1038/s41423-020-00534-2. Online ahead of print.
Liu, M., Zhou, J., Liu, X., Feng, Y., Yang, W., Wu, F., Cheung, O.K., Sun, H., Zeng, X., Tang, W., Mok, M.T., Wong, J., Yeung, P.C., Lai, P.B., Jin, H., Chen, J., Chan, S.L., Chan, A.W., To, K.F., Chen, Z., Sung, J.J., Chen, M., Cheng, A.S.* (2020). Targeting Monocyte-intrinsic Enhancer Reprogramming Improves Immunotherapy Efficacy in Hepatocellular Carcinoma. Gut, 69(2), 365-379.
Yuan, T., Yang, B., Qiu, W., Hao, Y., Zhang, Z., Yang, B., Li, N., Cheng, S., Lin, Z., Rui, Y.C., Cheung, O.K., Wu, W.K., Yang, W., Cheung, Y., Lai, P.B., Luo, J., Sung, J.J., Chen, R., Wang, H., Cheng, A.S.*, Yang P* (2019). ER-residential Nogo-B accelerates NAFLD-associated HCC mediated by metabolic reprogramming of oxLDL lipophagy. Nature Communications, 10(1), 3391.
Li, L., Gao, Y., Wu, Q., Cheng, A.S.*, Yip, K.Y.* (2019). New guidelines for DNA methylome studies regarding 5-hydroxymethylcytosine for understanding transcriptional regulation. Genome Research, 29(4), 543-555.
Xiong, L., Wu, F., Wu, Q., Xu, L., Cheung, O.K., Kang, W., Mok, M.T., Szeto, L.L.M., Lun, C.Y., Lung, R.W., Zhang, J., Yu, K.H., Lee, S.D., Huang, G., Wang, C.M., Liu, J., Yu, Z., Yu, D.Y., Chou, J.L., Huang, W.H., Feng, B., Cheung, Y.S., Lai, P.B., Tan, P., Wong, N., Chan, M.W., Huang, T.H., Yip, K.Y.*, Cheng, A.S.*, & To, K.F.* (2019). Aberrant enhancer hypomethylation contributes to hepatic carcinogenesis through global transcriptional reprogramming. Nature Communications, 10(1), 335.
Sun, H., Yang, W., Tian, Y., Zeng, X., Zhou, J., Mok, M.T.S., Tang, W., Feng, Y., Xu, L., Chan, A.W.H., Tong, J.H., Cheung, Y.S., Lai, P.B.S., Wang, H.K.S., Tsang, S.W., Chow, K.L., Hu, M., Liu, R., Huang, L., Yang, B., Yang, P., To, K.F., Sung, J.J.Y., Wong, G.L.H.*, Wong, V.W.S.*, Cheng, A.S.* (2018). An inflammatory-CCRK circuitry drives mTORC1-dependent metabolic and immunosuppressive reprogramming in obesity-associated hepatocellular carcinoma. Nature Communications, 9(1), 5214.
Lee, Y., Mok, M.T.S., Kang, W., Yang, W., Tang, W., Wu, F., Xu, L., Yan, M., Yu, Z., Lee, S.D., Tong, J.H., Cheung, Y.S., Lai, P.B., Yu, D.Y., Wang, Q., Wong, G.L., Chan, A.M., Yip, K.Y., To, K.F., Cheng, A.S.* (2018). Loss of tumor suppressor IGFBP4 drives epigenetic reprogramming in hepatic carcinogenesis. Nucleic Acids Research, 46, 8832-8847.
Zhou, J., Liu, M., Sun, H., Feng, Y., Xu, L., Chan, A.W.H., Tong, J.H., Wong, J., Chong, C.C.N., Lai, P.B.S., Wang, H.K., Tsang, S.W., Goodwin, T., Liu, R., Huang, L., Chen, Z., Sung, J.J., Chow, K.L., To, K.F., Cheng, A.S.* (2018). Hepatoma-intrinsic CCRK inhibition diminishes myeloid-derived suppressor cell immunosuppression and enhances immune-checkpoint blockade efficacy. Gut, 67, 931-944.
Cao, Q., Anyansi, C., Hu, X., Xu, L., Xiong, L., Tang, W., Mok, M.T.S., Cheng, C., Fan, X., Gerstein, M., Cheng, A.S., & Yip, K.Y. (2017). Reconstruction of enhancer-target networks in 935 samples of human primary cells, tissues and cell lines. Nature Genetics, 49, 1428-1436.
Yang, W., Mok, M.T., Li, M.S., Kang, W., Wang, H., Chan, A.W., Chou, J.L., Chen, J., Ng, E.K., To, K.F., Yu, J., Chan, M.W., Chan, F.K., Sung, J.J., Cheng, A.S.* (2016). Epigenetic silencing of GDF1 disrupts SMAD signaling to reinforce gastric cancer development. Oncogene, 35(16), 2133-2144.
Tian, Y., Wong, V.W., Wong, G.L., Yang, W., Sun, H., Shen, J., Tong, J.H., Go, M.Y., Cheung, Y.S., Lai, P.B., Zhou, M., Xu, G., Huang, T.H., Yu, J., To, K.F., Cheng, A.S.*, & Chan, H.L.* (2015). Histone deacetylase HDAC8 promotes insulin resistance and ß-catenin activation in NAFLD-associated hepatocellular carcinoma. Cancer Research, 75(22), 4803-4816.
Feng, H., Yu, Z., Tian, Y., Lee, Y.Y., Li, M.S., Go, M.Y., Cheung, Y.S., Lai, P.B., Chan, A.M., To, K.F., Chan, H.L., Sung, J.J., Cheng, A.S.* (2015). A CCRK-EZH2 epigenetic circuitry drives hepatocarcinogenesis and associates with tumor recurrence and poor survival of patients. Journal of Hepatology, 62(5), 1100-1111.
Yu, Z., Gao, Y.Q., Feng, H., Lee, Y.Y., Li, M.S., Tian, Y., Go, M.Y., Yu, D.Y., Cheung, Y.S., Lai P.B., Yu, J., Wong, V.W., Sung, J.J., Chan, H.L.*, Cheng, A.S. (2014). Cell cycle-related kinase mediates viral-host signalling to promote hepatitis B virus-associated hepatocarcinogenesis. Gut, 63(11), 1793-1804.
Ren, S.X.^#, Cheng, A.S.^#, To, K.F., Tong, J.H., Li, M.S., Shen, J., Wong, C.C., Zhang, L., Chan, R.L., Wang, X.J., Ng, S.S., Chiu, L.C., Marquez, V.E., Gallo, R., Chan, F.K., Yu, J., Sung, J.J., Wu, W.K., Cho, C.H. (2012). Host immune defense peptide LL-37 activates caspase-independent apoptosis and suppresses colon cancer. Cancer Research, 72(24), 6512-6523.
Cheng, A.S.*, Li, M.S., Kang, W., Cheng, V.Y., Chou, J.L., Lau, S.S., Go, M.Y., Lee, C.C., Ling, T.K., Ng, E.K., Yu, J., Huang, T.H., To, K.F., Chan, M.W., Sung, J.J., Chan, F.K.* (2013). Helicobacter pylori causes epigenetic dysregulation of FOXD3 to promote gastric carcinogenesis. Gastroenterology 144(1), 122-133.e9.
Feng, H., Cheng, A.S.*, Tsang, D.P., Li, M.S., Go, M.Y., Cheung, Y.S., Zhao, G.J., Ng, S.S., Lin, M.C., Yu, J., Lai, P.B., To, K.F., Sung, J.J.* (2011). Cell cycle–related kinase is a direct androgen receptor-regulated gene driving ß-catenin/T-cell factor-dependent hepatocarcinogenesis. Journal of Clinical Investigation, 121(8), 3159-3175.
Cheng, A.S.*, Lau, S.S., Chen, Y., Kondo, Y., Li, M.S., Feng, H., Ching, A.K., Cheung, P.K., Wong, K.H., Tong, J.H., Jin, H., Choy, R., Yu, J., To, K.F., Wong, N., Huang, T.H., Sung, J.J. (2011). EZH2-mediated concordant repression of Wnt antagonists promotes ß-catenin-dependent hepatocarcinogenesis. Cancer Research, 71(11), 4028-4039.
Cheng, A.S., Culhane, A.C., Chan, M.W., Venkataramu, C.R., Ehrich, M., Nasir, A., Rodriguez, B.A., Liu, J., Yan, P.S., Quackenbush, J., Nephew, K.P., Yeatman, T.J., Huang, T.H. (2008). Epithelial progeny of estrogen-exposed breast progenitor cells display a cancer-like methylome. Cancer Research, 68(6), 1786-1796.
Cheng, A.S., Jin, V.X., Fan, M.Y., Smith, L.T., Liyanarachchi, S., Yan, P.S., Leu, Y.W., Chan, M.W.Y., Plass, C., Nephew, K.P., Davuluri, R.V., Huang, T.H.M. (2006). Combinatorial analysis of transcription factor partners reveals recruitment of c-MYC to estrogen receptor α-responsive promoters. Molecular Cell, 21(3), 393-404.

* Corresponding / Co-corresponding author
# Co-first author

Grants

RGC – General Research Fund [PI; 01-Jan-21]: “Resistance to immune checkpoint targeting in hepatocellular carcinoma: Role of tumor interferon signalling” (HK$1,195,000).
AstraZeneca Pre-clinical Oncology Research Programme [PI; 01-Jan-21]: “Overcoming the PD-1/PD-L1 therapeutic resistance in hepatocellular carcinoma by BET inhibitor” (HK$400,000).
RGC – General Research Fund [PI; 01-Jan-20]: “Molecular and functional characterization of the immunoregulatory CCRK-mTOR pathway in NAFLD-associated hepatocellular carcinoma” (HK$1,049,917).
AstraZeneca Pre-clinical Oncology Research Programme [Co-PI; 01-Sep-19]: “Targeting the immunosuppressive tumor microenvironment by CXCR2 blockade for hepatocellular carcinoma therapy ” (HK$100,000).
Bristol-Myers Squibb (BMS) Pre-clinical Program [Co-PI; 01-Sep-19]: “Investigating the efficacy and mechanistic basis of BET and PD-1/PD-L1 co-blockade in fibrosis-associated hepatocellular carcinoma” (HK$100,000 in terms of drug).
Health and Medical Research Fund [PI; 24-Apr-19]: “A Novel Liver-specific PD-L1-trap Nanoparticle for Hepatocellular Carcinoma Immunotherapy” (HK$1,187,900).
RGC-Collaborative Research Fund (CRF) [PI; 21-Jan-19]: “Deciphering Enhancer Regulation of Tumor Immune Evasion to Develop New Combination Immunotherapies” (HK$6,990,790).
Celleron Therapeutics [PI; 01-Jan-19 to 31-Dec-20]: “Efficacy of combined CXD101, a class I HDAC inhibitor, and anti-PD-L1 immunotherapy in HCC orthotopic mouse model” (HK$282,000).
Terry Fox Cancer Research Funding [Co-PI; 31-Dec-18 to 30-Nov-20]: “Functional dissection of fibrosis-induced monocytic myeloid-derived suppressor cells (M-MDSCs) to develop new combination immunotherapy for hepatocellular carcinoma” (HK$1,200,000).
RGC – General Research Fund [PI; 01-Oct-16 to 31-Mar-19]: “Dissecting an Inflammatory-CCRK Circuitry in Non-alcoholic Fatty Liver Disease-related Hepatocarcinogenesis” (HK$763,612).
AstraZeneca UK Ltd / AstraZeneca Hong Kong Ltd [PI; 01-Apr-18 to 30-Mar-20]: “Enhancement of Hepatocellular Carcinoma Immunotherapy Through mTOR Inhibition” (HK$400,000).
RGC – Collaborative Research Fund (CRF) [PI; 01-Jun-15 to 31-May-18]: “Functional Liver Cancer Epigenomics: Exploiting Epigenetic Vulnerabilities for Therapeutics” (HK$7,418,375).
RGC – General Research Fund [PI; 01-Jul-14 to 30-Jun-17]: “Mechanistic characterization of liver cancer epigenome mediated by androgen receptor signaling” (HK$887,850).
Health and Medical Research Fund [PI; 15-Apr-14 to 14-Oct-15]: “Targeting H3K27 Trimethylation Epigenome for Liver Cancer Prevention” (HK$738,206).