Research Interests

Dr. Richard Yi Tsun KAO received his Ph. D. (Microbiology; under the supervision of Julian Davies) in 1999 from the University of British Columbia and subsequent postdoctoral training from Harvard Medical School. Richard joined the University of Hong Kong in 2001 as a Research Assistant Professor, first in HKU-Pasture Research Center, and later in the Department of Microbiology. Now he is the Assistant Professor in the Department of Microbiology and the Director of Chemical Genetics Unit, Research Center of Infection and Immunology, Li Ka Shing Faculty of Medicine, the University of Hong Kong. Currently Dr. Kao’s research focuses on the application of chemical genetics in infectious diseases. His work on SARS-associated coronavirus (SARS-CoV), which was published in Chemistry & Biology in 2004, has established the world’s first model of chemical genetics in virology and illustrated that chemical genetic approach could be employed to probe most, if not all, druggable targets of a pathogenic virus. After the SARS work, Dr. Kao’s team employed similar approach to identify new druggable targets in influenza viruses and published in Nature Biotechnology in 2010 an article detailing the groundbreaking discovery of influenza A nucleoprotein as a druggable antiviral target and the compound nucleozin as a potent antagonist of the nucleoprotein. This is also the first time that a study led by local researchers in Hong Kong is published in Nature Biotechnology.

● Application of chemical genetics in infectious diseases

● Novel Druggable targets in pathogenic microbes and antimicrobial drug discovery

● Antimicrobial biomaterials

Selected Publications

Tse, H., Kao, R.Y.T., Wu, W. L., Lim W.W.L., Chen, H., Yeung, J., To, K.K.W., Woo, P.C.Y., Sze, K.H., Yuen, K.Y. 2010. Structural basis and sequence co-evolution analysis of the hemagglutinin protein of pandemic influenza A/H1N1 (2009) virus. Exp Biol Med (In press).

Wong, R.W., Chen, Y., Hägg, U., McGrath, C., Seneviratne, C.J., Samaranayake, L., Kao, R. 2011. The antimicrobial efficacy of Fructus mume extract on orthodontic bracket:a monospecies-biofilm model study in vitro. Archives of Oral Biology. 56:16-21.

Liu, W.C., Wong, C.T., Fong, M.K., Cheung, W.S., Kao, R.Y.T., Luk, K.D.K., Lu, W.W. 2010. Gentamicin loaded strontium-containing hydroxyapatite (Sr-HA) bioactive bone cement - an efficient bioactive antibiotic drug delivery system. Journal of Biomedical Materials Research B. 95B: 397-406.

Kao, R.Y., Yang, D., Lau, L.S., Tsui, W.H.W., Hu, L., Dai, J., Chan, M.P., Chan, C.M., Wang, P., Zheng, B., Huang, J., Madar, J.C.S., Sun, J., Chen, G., Chen, H., Guan Y., and Yuen, K.Y. 2010. Identification of influenza A nucleoprotein as an antiviral target. Nature Biotechnology. 28:600-605.

Tong, W.Y., Liang, Y.M., Tam, V., Yip, H.K., Kao, R.Y.T., Cheung, K.M., Yeung, K.W., Lam, Y.W. 2010. Biochemical characterization of the cell-biomaterial interface by quantitative proteomics. Mol Cell Proteomics. 2010 Jun 20.

Wong, R.W., Hägg, U., Samaranayake, L., Yuen, M.K., Seneviratne, C.J., Kao, R. 2010. Antimicrobial activity of Chinese medicine herbs against common bacteria in oral biofilm. A pilot study. Int J Oral Maxillofac Surg. 39:599-605.

Ho, P.L., Lo, P.Y., Chow, K.H., Lau, E.H., Lai, E.L., Cheng, V.C., Kao, R.Y. 2010.Vancomycin MIC creep in MRSA isolates from 1997 to 2008 in a healthcare region in Hong Kong. J Infect. 60:140-145.

Lau, R.W., Ho, P.L., Kao, R.Y., Siu, G.K., Cheng, V.C., Yuen, K.Y., Yam, W.C. 2009. Rapid diagnosis of multidrug-resistant smear-positive pulmonary tuberculosis. Int J Antimicrob. Agents. 35:202-203.

Du, L, Kao, R.Y., Zhou, Y., He, Y., Zhao, G., Wong, C., Jiang, S., Yuen, K.Y., Jin, D.Y., Zheng, B.J. 2007. Cleavage of spike protein of SARS coronavirus by protease factor Xa is associated with viral infectivity. Biochem Biophys Res Commun. 359:174-179.

Hamill, P., Hudson, D., Kao, R.Y., Chow, P., Raj, M., Xu, H., Richer, M.J., and Jean, F. 2006. Development of a red-shifted fluorescence-based assay for SARS-coronavirus 3CL protease: identification of a novel class of anti-SARS agents from the tropical marine sponge Axinella corrugata. Biol Chem. 387:1063-1074.

Leung, T.Y., Ho P.L., Yuen, K.Y., Woo, W.L., Lam, T.H., Kao R.Y.T., Seto, W.H. and Yam, W.C. 2006. Molecular characterization of isoniazid resistance in Mycobacterium tuberculosis: identification of a novel mutation in inhA, Antimicrobial Agents and Chemotherapy 50: 1075-1078.

Hu, H., Li, L., Kao, R.Y., Kou, B., Wang, Z., Zhang, L., Zhang, H., Hao, Z., Tsui, W.H., Ni, A., Cui, L., Fan, B., Guo, F., Rao, S., Jiang, C., Li, Q., Sun, M., He, W., Liu, G. 2005. Screening and identification of linear B-cell epitopes and entry-blocking peptide of severe acute respiratory syndrome (SARS)-associated coronavirus using synthetic overlapping peptide library. J Comb Chem. 7: 648-656.

Woo, P.C., Lau, S.K., Wong, B.H., Tsoi, H.W., Fung, A.M., Kao, R.Y., Chan, K.H., Peiris, J.S., Yuen, K.Y. 2005. Differential sensitivities of severe acute respiratory syndrome (SARS) coronavirus spike polypeptide enzyme-linked immunosorbent assay (ELISA) and SARS coronavirus nucleocapsid protein ELISA for serodiagnosis of SARS coronavirus pneumonia. J Clin Microbiol. 43:3054-8.

Woo, P.C.Y., Ma, S.S.L., Teng, L.L., Li, W.S., Kao, R.Y.T., Lau, S.K.P. and Yuen, K.Y. 2005. Construction of an inducible expression shuttle vector for Laribacter hongkongensis, a novel bacterium associated with gastroenteritis, FEMS Microbiology Letters 252: 57-65.

Kao, R.Y., To, A.P.C., Ng, L.W.Y., Tsui, W.H.W., Lee, T.S.W., Tsoi, H.W., Yuen, K.Y. 2004. Characterization of SARS-CoV main protease and identification of biologically active small molecule inhibitors using a continuous fluorescence-based assay. FEBS Lett. 576:325-330.

Kao, R.Y., Tsui, W.H.W., Lee, T.S.W., Tanner, J.A., Watt, R.M., Hung, J.D., Hu, L.H., Chen, G.H., Chen, Z.W., Zhang, L.Q., He, T., Chan, K.H., Tse, H., To, A.P.C., Ng, L.W.Y., Wong, B.C.W., Tsoi, H.W., Yang, D., Ho, D.D., Yuen, K.Y. 2004. Identification of novel small molecule inhibitors of severe acute respiratory syndrome-associated coronavirus by chemical genetics. Chem. Biol. 11:1293-1299.

Chen, F., Chan, K.H., Jiang, Y., Kao, R.Y., Lu, H.T., Fan, K.W., Cheng, V.C.C., Tsui, W.H.W., Hung, I.F.N., Lee, T.S.W., Guan, Y., Peiris, J.S.M., Yuen, K.Y. 2004. In vitro susceptibility of ten clinical isolates of SARS coronavirus to selected antiviral compounds. J. Clin. Virol. 31:69-75.

Chu, C.M., Cheng, V.C.C., Hung, I.F.N., Wong, M.M.L., Chan, K.H., Chan, K.S., Kao, R.Y., Poon, L.L.M., Wong, C.L.P., Guan, Y., Peiris, J.S.M., Yuen, K.Y. 2004. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax. 59:252-256.

Teufel, D.P., Kao R., Acharya, K.R., Shapiro, R. 2003. Mutational Analysis of the Complex of Human RNase Inhibitor and Human Eosinophil-Derived Neurotoxin (RNase 2). Biochemistry. 42:1451-14599.

Jenkins, J.L., Kao, R., and Shapiro, R. 2003. Virtual screening to enrich hit lists from high-throughput screening: a case study on small molecule inhibitors of angiogenin. Proteins. 50: 81-83.

Kao, R, Jenkins, J.L., Olson, K.A., Key, M.E., Fett, J.W., and Shapiro, R. 2002. A small-molecule inhibitor of the ribonucleolytic activity of human angiogenin that possesses antitumor activity. Proc Natl Acad Sci U S A. 99:10066-10077.

Kao, R., Martínez-Ruiz, A., Martínez del Pozo, Á, Crameri, R., and Davies, J. 2001. Mitogillin and related ribotoxins. Methods in Enzymology. 341: 324-335.

Martínez-Ruiz, A., Garcia-Ortega, L., Kao, R., lacadena, J., Onaderra, M., Mancheno, J.M., Davies, J., and Martínez del Pozo, Á., and Gavilanes, J.G. 2001. RNase U2 and alpha-sarcin: close relatives. Methods in Enzymology. 341: 335-351.

Garcia-Ortega, L., Lacadena, J., Mancheno, J.M., Onaderra, M., Kao, R., Davies, J., Olmo, N., Martínez del Pozo, Á., and Gavilanes, J.G. 2001. Involvment of the amino-terminal b-harpin of the Aspergillus ribotoxins on the interaction with membranes and nonspecific ribonuclease activity. Protein Science. 10: 1658-1668.

Martinez-Ruiz, A., Garcia-Ortega, L., Kao, R., Onaderra, M., Mancheno, J.M., Davies, J., del Pozo, A.M., and Gavilanes, J.G. 2000. Ribonuclease U2: cloning, production in Pichia pastoris and affinity chromatography purification of the active recombinant protein. FEMS Microbiology Lett. 189: 165-169.

Kao, R. and Davies, J. 2000. The structures and properties of ribotoxins. In The Ribosome: structure, function, antibiotics, and cellular interactions. Edited by R. Garrett et al. ASM Press, Washington D.C. pp. 451-460.

Kao, R. and Davies, J. 2000. Single amino acid substitutions affecting the specificity of the fungal ribotoxin mitogillin. FEBS Lett. 466: 87-90. (a figure from the paper was selected as the front cover photograph of the journal)

Martínez-Ruiz, A., Kao, R., Davies, J., and Martínez del Pozo, Á. 1999. Ribotoxins are a more widespread group of proteins within the filamentous fungi than previous believed. Toxicon. 37: 1549-1563.

Kao, R. and Davies, J. 1999. Molecular dissection of mitogillin reveals that the fungal ribotoxins are a family of natural genetically-engineered ribonucleases. J. Biol. Chem. 274: 12576-12582.

Kao, R., Shea, J.E., Davies, J., and Holden, D.W. 1998. Probing the active site of mitogillin, a fungal ribotoxin. Mol. Microbiol. 29: 1019-1027.

Kao, R., and Davies, J. 1995. Fungal ribotoxins: a family of naturally engineered targeted toxins? Biochem. Cell Biol. 73: 1151-1159.

Invited Lectures in International Conferences:

“Identification of new druggable antiviral targets by chemical genetics”, at 24th International Conference on Antiviral Research, May 8-11, 2011 (Sofia, Bulgaria).

“Identification of influenza A nucleoprotein as a new antiviral target by chemical genetics”, at Influenza Congress USA-2010, November 9-10, 2010 (Washington D.C., USA).

“Identification of new antiviral targets by chemical genetics”, at International Conference on Antivirals for Neglected and Emerging Viruses ICAV -9, October 10-13, 2010 (Lubeck, Germany).

Keynote lecture: “Identification of new druggable targets in viral infections by chemical genetics”, at World Congress of Virus and Infections-2010, July 31-August 3, 2010 (Busan, Korea).

“New druggable targets, novel anti-flu compounds”, at World Summit of Antivirals-2008, July 20-26, 2008 (Kunming, Yunnan, China).

“New druggable targets, novel anti-flu compounds”, at Frontiers in Biomedical Research, December 13, 2007 (Hong Kong).

“Identification of novel small molecule compounds that differentially inhibit the yeast form of Penicillium marneffei”, at the 8th International Mycological Congress, August 21-25, 2006 (Cairns, Australia).

“Application of chemical genetics in virology – the SARS-CoV story”, at Drug Discovery Technology World Congress, August 8-11, 2005 (Boston, USA).

“Identification of novel small molecule inhibitors of SARS-CoV by chemical genetics”, at International Consortium of Antivirals, March 8-11, 2005 (Paris, France).

“Identification of novel small molecule inhibitors of SARS-CoV by chemical genetics”, at International Drug Discovery Science and Technology, November 1-4, 2004 (Beijing, China).

“Fungal ribotoxins: a family of naturally engineered targeted toxins?”, at Swiss Institute of Allergy and Asthma Research., July, 1996 (Davos, Switzerland).

“Site-directed mutagenesis of the mitogillin gene”, at Frontiers in Translation: An International Conference on the Structure and Function of the Ribosome, May, 1995 (Victoria, B.C., Canada).

Conference Papers:

Seneviratne C.J., Wong R.W.K., Hagg E.U.O., Kao R.Y.T. and Samaranayake L.P. Prunus mume extract exhibits antimicrobial activity against pathogenic oral bacteria, International Association for Dental Research (IADR), 88th General Session and Exhibition, Barcelona, Spain, July, 2010

Tsui Y.K., Leung Y.L., Kao R.Y.T., Masuda K., Chan D. and Cheung K.M.C. Identifying therapeutic chemical agents for osteoarthritis by high throughput screening, 55th Annual Meeting of the Orthopaedic Research Society, Las Vegas, USA, February 22-25, 2009

Yeung K.W.K., Leung K.Y., Kao R.Y.T., Chu P.K., Yip K., Luk K.D.K. and Cheung K.M.C. Feasibility Study of a New Plasma Coating to Suppress Bacterial Adhesion in Orthopaedic, Proceedings 4th International Conference on Technological Advances of Thin Films and Surface Coatings (ThinFilms 2008) (July 13-16, 2008), 2009, (Paper 4150) 35

Yeung K.W.K., Kao R.Y.T., Chu P., Luk K.D.K. and Cheung K.M.C. Oxygen Plasma Implanted Titanium Surface to Resist Staphylococcus Aureus Adhesion., 22nd European Conference on Biomaterials (ESB2009), Lausanne, Switzerland, 7-11Sep 2009. Oral presentation., 2009

Yeung K.W.K., Leung K.Y., Kao R.Y.T., Chu P.K., Luk K.D.K. and Cheung K.M.C. A Novel Plasma Surface Treatment to Suppress Bacterial Adhesion on Titanium Alloy., Society for Biomaterials 2009 Annual Meeting and Exposition, San Antonio, Texas, 22-25Apr2009. Poster presentation., 2009, Paper 37

Tsui Y.K., Leung Y.L., Kao R.Y.T., Masuda K., Chan D. and Cheung K.M.C. Identification of Therapeutic Agents for the treatment of Osteoarthritis with the Application of High-Throughput Screening, 54th Annual Meeting of the Orthopaedic Research Society, San Francisco, USA, 2008

Leung K.Y., Yeung K.W.K., Kao R.Y.T., Chu P.K. and Cheung K.M.C. Optimal local dosage of housekeeping antibiotics to inhibit S. aureus without inducing osteoblast necrosis: in vitro study, SICOT/SIROT 2008 XXIV Triennial World Congress, Hong Kong, August 24-28, 2008

Leung K.Y., Yeung K.W.K., Kao R.Y.T., Chu P.K. and Cheung K.M.C. An anti-bacterial coating in dental implant used in orthopaedics/ feasibility study of anti-bacterial coating in dental implant for orthopaedic use, SICOT/SIROT 2008 XXIV Triennial World Congress, Hong Kong (Aug 24-28, 2008), 2008

Leung K.Y., Yeung K.W.K., Kao R.Y.T., Chu P.K. and Cheung K.M.C. Optimal local dosage of housekeeping antibiotics to inhibit s. aureus without inducing osteoblast necrosis: in vitro study., SICOT/SIROT 2008 XXIV Triennial World Congress, Hong Kong (Aug 24-28, 2008), 2008

Leung K.Y., Yeung K.W.K., Kao R.Y.T., Chu P.K. and Cheung K.M.C. An anti-bacterial coating in dental implant used in orthopaedics/feasibility study of anti-bacterial coating in detnal implant for orthopaedic use, SICOT/SIROT 2008 XXIV Triennial World Congress, Hong Kong, August 24-28, 2008

Lau L.S., Tsui W., Guan Y., Yang D., Yuen K.Y. and Kao R.Y. Identification of small molecule inhibitors of influenza A viruses by chemical genetics, 32nd Congress of the Federation-of-European-Biochemical-Societies (FEBS), Vienna, Austria, 2007.

Tanner J.A., Watt R.M., Kao R.Y.T. and Huang J. Targeting the SARS Coronavirus Helicase - Three Approaches to Inhibitor Development, FASEB Journal, 2005, 217.9