Education

Current Positions

• Associate Professor, School of Life Sciences, CUHK
• Programme Director, Biochemistry Programme, School of Life Sciences, CUHK

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

• Cai, G., Bao, Y., Li, Q., Hsu, P.H., Xia, J., and Ngo, J.C.K.(2024) Design of a covalent protein-protein interaction inhibitor of SRPKs to suppress angiogenesis and invasion of cancer cells. Communications Chemistry, 7:144.
• Yip, R.P.H., Kwok, D.C.Y., Lai, L.T.F., Ho, S.M., Wong, I.C.K., Chan, C.P., Lau, W.C.Y., and Ngo, J.C.K.(2024) SRPK2 mediates HBV core protein phosphorylation and capsid assembly via docking interaction. PLOS Pathogens, 20(2):e1011978.
• An, Y., Chen, Z.F., Chan, H.Y.E.*, and Ngo, J.C.K.*(2022) Molecular insights into the interaction of CAG trinucleotide RNA repeats with nucleolin and its implication in polyglutamine diseases. Nucleic Acids Research, 50(13), 7655-7668. (*Co-corresponding author)
• Peng, S., Guo, P., Lin, X., An, Y., Sze, K.H., Lau, M.H.Y., Chen, Z.S., Wang, Q., Li, W., Sun, J.K., Ma, S.Y., Chan, T.F., Lau, K.F., Ngo, J.C.K., Kwan, K.M., Wong, C.H., Lam, S.L., Zimmerman, S.C., Tuccinardi, T., Zuo, Z., Au-Yeung, H.Y., Chow, H.M., Chan, H.Y.E. (2021) CAG RNAs induce DNA damage and apoptosis by silencing NUDT16expression in polyglutamine degeneration. Proc Natl Acad Sci U S A, 118(19), e2022940118.
• Li, Q., Zeng C., Liu, H., Yung, K.W.Y., Chen, C., Xie, Q., Yu, Zhang, Y., Wan, S.W.C., Mak, B.S.W., Xia, J., Xiong, S., and Ngo, J.C.K.(2020) Protein-protein interaction inhibitor of SRPKs alters the splicing isoforms of VEGF and inhibits angiogenesis. iScience, 24, 102423.
• Chau, D.D.L., Yung, K.W.Y., Chan, W.W.L., An, Y., Hao, Y., Chan, H.Y.E., Ngo, C.K.*, and Lau K.F. (2019) Attenuation of amyloid-bgeneration by atypical protein kinase C-mediated phosphorylation of engulfment adaptor PTB domain containing 1 threonine 35. The FASEB Journal, 33(11):12019-12035. (*Co-corresponding author)
• 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.(2019) 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.
• Chen, Z.S., Li, L., Peng, S., Chen, F.M., Zhang, Q., An, Y., Lin, X., Li, W., Koon, A.C., Chan, T.F., Lau, K.F., Ngo, J.C.K., Wong, W.T., Kwan, K.M., Chan, H.Y.E. (2018) Planar cell polarity gene Fuz triggers apoptosis in neurodegenerative disease models. EMBO Reports. 19(9):e45409.
• 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. 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.
• 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.  Model Mech., 9,321-334.
• Liang, N., Zheng, C., Tao, K.P., Sou, W.H., Hsia, H.P., Qu, D., Lau, S.N., and Ngo, 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.
• 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

• Principal Investigator, RGC General Research Fund; 2025-27
  Project title: Regulation of phosphorylation of the essential splicing factor SRSF2 by SRPK2 
• Principal Investigator, RGC General Research Fund; 2024-26
  Project title: Effects of a covalent inhibitor that targets the splicing kinases SRPKs
• Principal Investigator, RGC General Research Fund; 2022-24
  Project title: Functional roles of SRPK2 in epithelial-mesenchymal transition and cell migration 
• Co-Principal Investigator, Food and Health Bureau – Health and Medical Research Fund; 2021-24
  Project title: Targeting the interaction between engulfment adaptor phosphotyrosine-binding domain-containing protein 1 and autophagy-related protein 14 to reduce the generation of amyloid -beta in Alzheimer’s disease
• Co-Principal Investigator, Special Funds for Technological Innovation Strategy of Guangdong Province in 2020-21
  Project title: Development of long-term sustained-release active peptide conjugated selenium nanoparticles SeNPs-CTS-DBAYL with enhanced therapeutic effect for insulin resistance.
• Co-Principal Investigator, Science and Technology Development Fund, Macau 2020-22
  Project title: Mechanistic Study of NFkappaB and Oncoprotein Bcl3 in Transcriptional Regulation
• Principal Investigator, RGC General Research Fund; 2019-22
  Project title: Rational design of a covalent inhibitor that targets the protein-protein interaction site of the splicing kinase SRPK1 and its substrates. 
• Co-Principal Investigator, RGC Collaborative Research Fund; 2019-22
  Project title: A state-of-the-art X-ray diffraction facility for structural biology research in Hong Kong.
• Principal Investigator, RGC General Research Fund; 2017-20
  Project title: 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. 
• Co-Principal Investigator, RGC Collaborative Research Fund; 2017-19
  Project title: The first integrated cryo-EM and cryo-ET shared facility for life sciences research in Hong Kong.
• Principal Investigator, RGC General Research Fund; 2015-17
  Project title: Investigation of the different phosphorylation mechanisms of SR proteins by SRPKs. 
• Co-Principal Investigator, RGC Collaborative Research Fund; 2014-2017
  Project title: Targeting RNA and protein toxicities of polyglutamine diseases using peptidylic inhibitors. 
• Co-Investigator, Food and Health Bureau – Health and Medical Research Fund; 2014-16
  Project title: Structure-based discovery of inhibitors of Helicobactor pylori urease maturation. 
• Co-Investigator, Food and Health Bureau – Health and Medical Research Fund; 2014-16
  Project title: Structure-based drug design of anti-influenza compounds targeting influenza polymerase.
• Co-Investigator, Food and Health Bureau – Health and Medical Research Fund; 2014-16
  Project title: An inhibitory peptide approach to simultaneously target RNA and protein toxicities in polyglutamine degeneration. 
• Co-Investigator I, The Danish Lundbeck Foundation; 2011-2014
  Project title: New principles for pharmacological intervention with blood coagulation and fibrinolysis: Targeting new types of molecular interactions with new types of agents
• Principal Investigator, RGC General Research Fund; 2011-14
  Project title: Regulation and phosphorylation of SR proteins by SRPK2.
• Principal Investigator, Research Fund for the Control of Infectious Diseases; 2011-13
  Project title: Search of inhibitors that target HIV pre-mRNA splicing to overcome drug resistance 
• Co-Investigator, Research Fund for the Control of Infectious Diseases; 2010-12
  Project title: In silico structure-based screening and characterization of inhibitors for influenza A virus nucleoprotein and RNA polymerase. 
• Principal Investigator, RGC General Research Fund; 2010-12
  Project title: Structural and functional studies of SR Protein Kinase 2: A key factor in the regulation of pre-mRNA splicing of cellular and viral proteins.