陈居明 - 香港城市大学 - 生物医学科学系

个人简介

Dr 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.

研究领域

1) the role of epigenetics in regulating gene expression and human diseases and 2) how epigenetic information in 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. The two 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)

近期论文

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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 https://doi.org/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 https://doi.org/10.1038/s41392-020-0131-0 (@ Nature Publishing Group) 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. doi: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 doi: 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 doi: 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 Apr30 doi.org/10.1016/j.jgg.2018.04.004 Wan YCE, Liu J, Chan KM#. (2018) Histone H3 mutations in cancer. Curr Pharmacol Rep 2018. doi.org/10.1007/s40495-018-0141-6 (Corresponding author) 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 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 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 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 Jun12 22,1176-90 Recommended by Faculty of 1000, F factor 8.0 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 Apr27;287(18): 15024-33 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 Wong XHL, Cao R Jin GX, Chan KM, Cao Y, Zhou ZJ. (2012) When MT1-MMP meets ADAMs. Cell Cycle 11:15, Aug1,1-6 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 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 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 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 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. 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.