Professor NGO Chi Ki Jacky

Address
    

(Office): Rm E403, Science Centre East Block

(Lab): Rm 118, Run Run Shaw Science Building
    People NCK
 

Phone
    

(Office): (852) 3943 6346

(Lab): (852) 3943 1349
Fax     (852) 2603 7246
Email     jackyngo@cuhk.edu.hk
Web     -
     

 
Education
2006     Ph.D., University of California San Diego
2003     M.Sc., University of California San Diego
2000     B.Sc., University of California San Diego

Position

     Associate Professor, School of Life Sciences


Research Interests

    Determining the structure, function, and mechanism of proteins that involve in the regulation of pre-mRNA splicing using a multidisciplinary approach combining X-ray crystallography and cryo-EM with biochemical and biological studies.
    Target-based discovery and development of inhibitors for molecular targets in cancers and neurodegenerative diseases; and investigation of the structures and mechanisms of the inhibitors.


Representative Publications

    Zhang, Q., An, Y., Chen, Z.F.S., Koon, A.C., Lau, K.F., Ngo, J.C.K.*, and Chan, H.Y.E. (2019) A peptidylic inhibitor for neutralizing r(GGGGCC)exp-associated neurodegeneration in C9ALS-FTD. Molecular Therapy Nucleic Acids, 16, 172-185. (*Co-corresponding author)
    Long, Y., Sou, W.H., Yung, K.W.Y., Liu, H., Wan, S.W.C., Li, Q., Zeng, C., Chan, G.H.C., Law, C.O.K., Lau, T.C.K., Ngo, J.C.K. (2018) Distinct mechanisms govern the phosphorylation of different SR splicing factors. Journal of Biological Chemistry, 294(4), 1312-1327.
    Li, W., Tam, K.M.V., Chan, W.W.R., Koon, A.C., Ngo, J.C.K., Chan, H.Y.E., and Lau, K.F. (2018) Neuronal adaptor FE65 stimulates Rac1-mediated neurite outgrowth by recruiting and activating ELMO1. Journal of Biological Chemistry, 293, 7674-7688.
    Hatcher, J.M., Wu, G., Zeng, C., Zhu, J., Meng, F., Patel, S., Wang, W., Ficarro, S.B., Leggett, A.L., Powell, C., Marto, J.A., Zhang, K., Ngo, J.C.K., Fu, X., Zhang, T., and Gray, N. (2018).  SRPKIN-1: A covalent SRPK1/2 inhibitor that potently covers VEGF from pro-angiogenic to anti-angiogenic form. Cell Chemical Biology. 25,460-470.
    Zhang, Q., Chen, Z.S., An, Y., Liu, Hou, Y., Li, W., Lau, K.F., Koon, A., Ngo, J.C.K.*, and Chan, H.Y.E. (2018). A peptidylic inhibitor for neutralizing expanded CAG RNA-induced nucleolar stress in polyglutamine diseases. RNA. 24(4):486-498. (*Co-corresponding author)
    Zhang, Q., Yang, M, Sorensen, K.K., Madsen, C.S., Boesen, J.T., An, Y., Peng, S.H., Wei, Y., Jensen, K.J., Zuo, Z.J., Chan, H.Y.E., and Ngo, J.C.K. (2017)  A brain-targeting lapidated peptide for neutralizing RNA-mediated toxicity in polyglutamine disease. Scientific Reports. 7:12077.
    Lui, M., Lo, C.Y., Wang, G., Chow, H.F., Ngo, J.C.K., Wan, D.C.C., Poon, L.L.M., and Shaw, P.C. (2017). Identification of influenza polymerase inhibitors targeting polymerase PB2 cap-binding domain through virtual screening. Antiviral Research. 144, 186-195.
    Kromann-Hansen, T., Oldenburg, E., Yung, K.W.Y., Ghassabeh, G.H., Muyldermans, S., Declerck, P.J., Huang, M.D., Andreasen, P.A., and Ngo, J.C.K. (2016). A camelid-derived antibody fragment targeting the active site of a serine protease balances between inhibitor and substrate behaviour. Journal of Biological Chemistry. 291, 15156-15168.
    Zhang, Q., Tsoi, H., Peng, S., Li, P.P., Lau, K.F., Rudnicki, D.D., Ngo, J.C.K., Chan, H.Y. (2016) A peptidylic inhibitor-based therapeutic approach that simultaneously suppresses RNA- and protein-mediated toxicities in polyglutamine diseases. Dis. Model Mech., 9,321-334.
    Chow, W.N., Ngo, J.C.K., Li, W., Chen, Y.W., Tam, K.M., Chan, H.Y., Miller, C.C., Lau, K.F. (2015) Phosphorylation of FE65 Ser610 by serum- and glucocorticoid-induced kinase 1 modulates Alzheimer's disease amyloid precursor protein processing. Biochemical Journal. 470, 303-17.
    Liang, N., Zheng, C., Tao, K.P., Sou, W.H., Hsia, H.P., Qu, D., Lau, S.N., and Ngo, J.C.K. (2014). Primary structural features of SR-like protein AcinusS define the phosphorylation mechanism by SRPK2. Biochemical Journal, 459, 181-191.
    Zhao, B., Yuan, C., Li, R., Qu, D., Huang, M., and Ngo, J.C.K. (2013) Crystal structures of matriptase in complex with its inhibitor hepatocyte growth factor activator inhibitor-1. Journal of Biological Chemistry, 288(16); 11155-11164.
    Yuan, C., Cheng, L., Meehan, E., Daly, N., Craik, D.J., Huang, M., Ngo, J.C.K. (2011) Structure of catalytic domain of Matriptase in complex with Sunflower trypsin inhibitor-1. BMC Structural Biology, 11:30.
    Ngo, J.C.K., Jiang, L., Lin, Z., Yuan, Cai., Chen, Z., Zhang, X., Yu, H., Wang, J., Lin, L., Huang, M. (2011). Structural basis for therapeutic intervention of uPA/uPAR system. Current Drug Targets,12(12), 1729-43.
    Ngo, J.C.K., Huang, M.D., Roth, D.A., Furie, B.C. and Furie, B. (2008) Crystal structure of human factor VIII: Implications for the formation of the factor IXa:factor VIIIa complex. Structure, 16, 597-606.
    Ngo, J.C.K., Giang, K., Chakrabarti, S.,  Ma, C.T., Huynh, N., Hagopian, J.C., Dorrestein, P.C., Fu, X.D., Adams, J..A. and Ghosh, G. (2008) A sliding docking interaction is essential for sequential and processive phosphorylation of an SR protein by SRPK1. Molecular Cell, 29, 563-576.
    Ngo, J.C.K., Gullingsrud, J., Giang, K., Yeh, M. J., Fu, X.D.,  Adams, J.A., McCammon, J.A. and Ghosh, G. (2007) SR protein kinase 1 is resilient to inactivation. Structure, 15, 123-133.
    Ngo, J.C.K., Chakrabarti, S., Ding J.H., Velazquez-Dones A., Nolen, B., Aubol, B.E., Adams, J.A., Fu, X.D. and Ghosh, G. (2005) Interplay between SRPK and Clk/Sty kinases in phosphorylation of the splicing factor ASF/SF2 is regulated by a docking motif in ASF/SF2. Molecular Cell, 20, 77-89 (Cover).

Research Grants

    2017-20 RGC General Research Fund; Investigation of the interaction and phosohorylation mechanisums of Hepatitis B virus core protein by SR protein kinase 2 and the roles of their interaction in HBV replication.
    2015-17 RGC General Research Fund; Investigation of the different phosphorylation mechanisms of SR proteins by SRPKs.
    2011-14 RGC General Research Fund; Regulation and phosphorylation of SR proteins by SRPK2.
    2011-13 Research Fund for the Control of Infectious Diseases; Search of inhibitors that target HIV pre-mRNA splicing to overcome drug resistance
    2010-12 RGC General Research Fund; Structural and functional studies of SR Protein Kinase 2: A key factor in the regulation of pre-mRNA splicing of cellular and viral proteins.