CHAN, Kui Ming (陳居明)

Prof. K. M. CHAN graduated with BSc and received his PhD at the department of Biochemistry, HKU. He then moved to Mayo Clinic (Rochester MN, USA) for postdoctoral training and obtained the Edward C. Kendall Research Fellowship in Biochemistry before rejoining HKU as Research Assistant Professor in June 2013. In February 2015 he joined the Department of Biomedical Sciences (BMS), City University of Hong Kong as a tenure-track Assistant Professor.

Research Interests

Prof. Chan is interested in understanding 1) the role of epigenetics in regulating gene expression and human diseases and 2) how epigenetic information is maintained during cell division. It is well known that genetic information is encoded by the DNA sequence. However, DNA alone does not account for the complexity of the mammalian genome. Chromatin, comprising DNA, core histones and other regulatory proteins, regulates gene expression and maintains genome stability. Recent studies including ours have used the next generation sequencing technologies and the CRISPR-Cas9 approach to elucidate the mechanisms of mutant histones in the development of brain and bone cancers. We are currently focusing on identifying new cancer driving histone mutations and discovering therapeutics for these diseases using different animal models. Another major research direction is the development of novel genome-wide screening/editing platforms to elucidate the significance of gene function in living animals in vivo

The three major research directions in the lab:

• Decipher the mechanisms of oncohistones (H3 and H2B) in cancer development
• Identify and elucidate the mechanisms of novel protein factors in X chromosome inactivation (XCI)
• Development of novel genome-wide editing/screening platforms in living animals in vivo.

Position Available

We are looking for Postdoctoral Fellows, Research Assistants and Postgraduate Students to join our team. Interested candidates please send your CV and a summary of past research experience to Prof. Chan: (email: ming.chan@cityu.edu.hk)

Selected Publications

2023

• Suyang Zhang, Feng Yang, Yile Huang, Liangqiang He, Yuying Li, Yi Ching Esther Wan, Yingzhe Ding, Kui ming Chan, Ting Xie, Hao Sun, Huating Wang (2023) ATF3 Induction Prevents Precocious Activation of Skeletal Muscle Stem Cell by Regulating H2B Expression. Nat Commun (accepted)
• Congcong Tian, Jiaqi Zhou, Xinran Li, Yuan Gao, Qing Wen, Xing Kang, Nan Wang, Yuan Yao, Jiuhang Jiang, Guibing Song, Tianjun Zhang, Suili Hu, JingYi Liao, Chuanhe Yu, Zhiquan Wang, Xiangyu Liu, Xin-Hai Pei, Kui Ming Chan, Zichuan Liu, Haiyun Gan (2023) Impaired histone inhertance promotes tumor progression. Nat Commun (In press)

2022

• Xuanming Guo, Jianli Cao, Jian-Piao Cai , Jiayan Wu, Jiangang Huang, Pallavi Asthana, Sheung Kin Ken Wong, Zi-Wei Ye, Susma Gurung, Yijing Zhang, Sheng Wang, Zening Wang, Xin Ge, Hiu Yee Kwan, Aiping Lyu, Kui Ming Chan, Nathalie Wong, Jiandong Huang, Zhongjun Zhou, Zhao-Xiang Bian, Shuofeng Yuan, Hoi Leong Xavier Wong (2022) Control of SARS-CoV-2 infection by MT1-MMP-mediated shedding of ACE2. Nat Commun DOI: 10.1038/s41467-022-35590-x
• Lixiang Zhai, Chunhua Huang, Ziwan Ning, Yijing Zhang, Min Zhuang, Wei Yang, Xiaolei Wang, Jingjing Wang, Lu Zhang, Haitao Xiao, Ling Zhao, Pallavi Asthana, Yan Y. Lam, Chi Fung Willis Chow, Jian-dong Huang, Shuofeng Yuan, Kui Ming Chan, Chun-Su Yuan, Johnson Yiu-Nam Lau, Hoi Leong Xavier Wong, Zhao-xiang Bian. (2022) Ruminococcus gnavus plays a pathogenic role in diarrhea-predominant irritable bowel syndrome by increasing serotonin biosynthesis. Cell Host Microbe DOI: 10.1016/j.chom.2022.11.006
• Su Zhang, Yang Meng, Lian Zhou, Lei Qiu, Heping Wang, Dan Su, Bo Zhang, Kui Ming CHAN, Junhong Han. (2022) Targeting epigenetic regulators for inflammation: Mechanisms and intervention therapy. MedComm DOI: 10.1002/mco2.173
• Shuyi MAI, Xiaoxuan ZHU, Esther Yi Ching WAN, Shengyu WU, Jesslyn Nagalin Yonathan, Ying LI, Jun WANG, Jessica Yuen Wuen MA, Bing ZUO, Dennis Yan-yin TSE, Pui-Chi LO, Xin WANG, Kui Ming CHAN, David M. WU, Wenjun XIONG. (2022) Postnatal eye size in mice is controlled by SREBP2-mediated transcriptional repression of Lrp2 and Bmp2. Development DOI: 10.1242/dev.200633
• Kang TZE, Wan YCE, Zhang Z, Chan KM. (2022) Lrwd1 impacts cell proliferation and the silencing of repetitive DNA elements. Genesis DOI: 10.1002/dvg.23475

2021

• Hu J, Lai Y, Huang H, Ramakrishnan S, Pan Y, Ma VW, Cheuk W, So GYK, He Q, Lau CG, Zhang L, Cho WCS, Chan KM, Wang X, Chin YR. (2021) TCOF1 upregulation in triple-negative breast cancer promotes stemness and tumor growth, and correlates with poor prognosis. Br J Cancer DOI: 10.1038/s41416-021-01596-3
• Li X, Zhou J, Zhao W, Wen Q, Wang W, Peng H, Gao Y, Bouchonville KJ, Offer SM, Chan KM, Wang Z, Li N, Gan H. (2021) Defining proximity proteomics of histone modifications by antibody-mediated protein A-APEX2 labeling. Genomics, Proteomics & Bioinformatics DOI: 10.1016/j.gpb.2021.09.003
• Yao Y, Wen Q, Zhang T, Yu C, Chan KM, Gan H. (2021) Advances in Approaches to study chromatin mediated epigenetic memory. ACS Synthetic Biology DOI: 10.1021/acssynbio.1c00394
• Wan YCE, Chan KM#. (2021) Histone H2B mutations in Cancer. Biomedicines 9(6), 694. DOI: 10.3390/biomedicines9060694
• Huang H, Hu J, Maryam, A, Huang Q, Zhang Y, Ramakrishnan S, Li J, Ma H, Ma VWS, Cheuk W, So GYK, Wang W, Cho WCS, Zhang L, Chan KM, Wang Xin, Chin YR. (2021) Defining super-enhancer landscape in triple-negative breast cancer by multiomic profiling. Nature Communications DOI: 10.1038/s41467-021-22445-0
• Kang TZE, Zhu L, Yang D, Ding D, Zhu X, Wan YCE, Liu J, Ramakrishnan S, Chan LL, Chan SY, Wang X, Gan H, Han J, Ishibashi T, Li Q, Chan KM#. (2021) The elevated transcription of ADAM19 by the oncohistone H2BE76K contributes to oncogenic properties in breast cancer. Journal of Biological Chemistry DOI: 10.1016/j.jbc.2021.100374

2020

• Wan YCE, Liu J, Zhu L, Kang TZE, Zhu X, Lis J, Ishibashi T, Danko CG#, Wang X#, Chan KM#. (2020) The H2BG53D oncohistone directly upregulates ANXA3 transcription and enhances cell migration in Pancreatic Ductal Adenocarcinoma. Signal Transduction and Targeted Therapy 10.1038/s41392-020-00219-2
• Yi W, Li J, Zhu X, Wang X, Fan L, Sun WJ, Liao L, Zhang J, Li X, Ye J, Chen F, Taipale J, Chan KM#, Zhang L#, Yan J# (2020) CRISPR-Assisted Detection of RNA-Protein interactions in living cells. Nature Methods. (#Co-corresponding author) https://doi.org/10.1038/s41592-020-0866-0
• Wan YCE, Leung TCS, Ding DB, Sun XL, Zhu L, Kang TZE, Yang D, Zhang YC, Qian CM, Huen MSY, Li Q, Chow MZY, Zheng ZL, Han JH, Goel A, Wang X#, Ishibashi T#, Chan KM#. (2020) Cancer associated histone mutation H2BG53D disrupts DNA-histone octamer interaction and promotes oncogenic phenotypes. Signal Transduction and Targeted Therapy 10.1038/s41392-020-0131-0 (@ Nature Publishing Group)

2018

• Liu H, So J, Peng L, Tsang KH, Mak P, Chan KM#, Chan SY#. (2018) SPYL2 Regulates the expression of EZH2 target genes in neurons. Molecular Neurobiology 2018 Jul 26 10.1007/s12035-018-1238-y (#Co-corresponding author)
• An L, Li J, Dong C, Chen J, Yuan J, Chan KM, Yu C, Legube G, Stark J, Huen MS. (2018) RNA169 limits 53BP1 at DSBs to stimulate single-strand annealing repair. PNAS 2018 10.1073/pnas.1804823115
• Li S, Xu Z, Xu J, Wang X, Yu C, Zheng P, Zho L, Gan H, Li L, Sharma S, Chabes A, Li D, Yang J, Chen Y, Wang S, Sun Y, Zheng S, Li J, Chen X, Han J, Chan KM, Qi Z, Feng J, Li Q. (2018) Rtt105 functions as a chaperone for replication protein A to preserve genome stability. EMBO J 2018 10.15252/embj.201899154
• Qiu L, Hu X, Jing Q, Zeng X, Chan KM, Han J. (2018) Mechanism of cancer: Oncohistones in action. J Genet Genomics 2018 Apr 30 10.1016/j.jgg.2018.04.004
• Wan YCE, Liu J, Chan KM#. (2018) Histone H3 mutations in cancer. Curr Pharmacol Rep 10.1007/s40495-018-0141-6 (Corresponding author)

Other Publications

1. Stunnenberg HG; International Human Epigenome Consortium, Hirst M et al., (2016) The International Human Epigenome Consortium: A Blueprint for Scientific Collaboration and Discovery. Cell 2016; 167: 1145-49
2. Chan KM, Han G, Fang D, Gan H, Zhang Z. (2013) A lesson learned from the H3.3K27M mutation found in pediatric glioma: a new approach to the study of the function of histone modifications in vivo. Cell Cycle. 2013 Jul 10; 12(16): 2546-52
3. Chan KM, Fang D, Gan H, Hashizume R, Yu C, Schroeder M, Gupta N, Mueller S, James CD, Jenkins R, Sarkaria J, Zhang Z. (2013) The histone H3.3K27M mutation in pediatric glioma reprograms H3K27 methylation and gene expression.  Genes & Dev. 2013. 27: 985-990
4. Chan KM, Wong XHL, Jin GX, Liu BH, Cao R, Cao Y, Tryggvason K, Zhou ZJ. (2012) MT1-MMP Inactivates ADAM9 to Regulate FGFR Signaling and Calvarial Osteogenesis, Developmental Cell, 2012 Jun 12; 22, 1176-90. Recommended by Faculty of 1000, F factor 8.0
5. Chan KM, Zhang Z. (2012) Leucine-rich repeat and WD repeat-containing protein 1 is recruited to pericentric heterochromatin by trimethylated lysine 9 of histone H3 and maintains heterochromatin silencing, J Biol Chem 2012 Apr 27; 287(18): 15024-33
6. Chan KM, Zhang H, Malureanu L, van Deursen J, Zhang Z. (2011) Diverse factors are involved in maintaining X chromosome inactivation. Proc Natl Acad Sci U S A. 2011 Oct 4; 108(40):16699-704
7. Wong XHL, Cao R Jin GX, Chan KM, Cao Y, Zhou ZJ. (2012) When MT1-MMP meets ADAMs. Cell Cycle 11:15, Aug 1, 1-6
8. Jin G, Zhang F, Chan KM, Xavier Wong HL, Liu B, Cheah KS, Liu X, Mauch C, Liu D, Zhou Z. (2011) MT1-MMP cleaves Dll1 to negatively regulate Notch signalling to maintain normal B-cell development. EMBO J. 2011 Jun 1; 30(11):2281-93. Epub 2011 May 13
9. Sugiyama N, Varjosalo M, Meller P, Lohi J, Chan KM, Zhou Z, Alitalo K, Taipale J, Keski-Oja J, Lehti K. (2010) FGF receptor-4 (FGFR4) polymorphism acts as an activity switch of a membrane type 1 matrix metalloproteinase -FGFR4 complex. Proc Natl Acad Sci U S A. 2010 Sep 7; 107(36):15786-91
10. West MA, Prescott AR, Chan KM, Zhou Z, Rose-John S, Scheller J, Watts C. (2008) TLR ligand-induced podosome disassembly in dendritic cells is ADAM17 dependent. J Cell Biol 2008 Sep 8; 182(5):993-1005
11. Liu B, Wang J, Chan KM, Tjia WM, Deng W, Guan X, Huang JD, Li KM, Chau PY, Chen DJ, Pei D, Pendas AM, Cadiñanos J, López-Otín C, Tse HF, Hutchison C, Chen J, Cao Y, Cheah KS, Tryggvason K, Zhou Z. (2005) Genomic instability in laminopathy-based premature aging. Nat Med 2005 Jul; 11(7):780-5. Epub 2005 Jun 26
12. Zhou Z, Wang J, Cao R, Morita H, Soininen R, Chan KM, Liu B, Cao Y, Tryggvason K. (2004) Impaired angiogenesis, delayed wound healing and retarded tumor growth in perlecan heparan sulfate-deficient mice. Cancer Res 2004 Jul 15; 64(14):4699-702.
13. Zhou Z, Doi M, Wang J, Cao R, Liu B, Chan KM, Kortesmaa J, Sorokin L, Cao Y, Tryggvason K. (2004) Deletion of laminin-8 results in increased tumor neovascularization and metastasis in mice. Cancer Res. 2004 Jun 15; 64(12):4059-63.

1 August 2023