ASY Lau Allan SY Lau, M.D.

Professor, Cytokine Biology Group, Department of Paediatrics
Professor, Department of Pharmacology and Pharmacy
Director, Molecular Chinese Medicine Laboratory
Li Ka Shing Faculty of Medicine
University of Hong Kong, Hong Kong, China

Dr. Lau is a graduate of McGill University Medical School with degrees in Biochemistry and Medicine. He trained in Pediatrics (FRCP), Infectious Diseases and Immunobiology research at UCSF and the Hospital for Sick Children, Toronto. He was an MRC Fellow in the University of Toronto. Prior to returning to Hong Kong in 2001, he was on faculty in University of Toronto and UCSF.

Current Research Interests:

  1. Immune response to microbial infections – HIV and Mycobacterial interactions
  2. Biology of interferon and cytokines - signaling pathways and gene regulation
  3. Platform Technology for investigating Bioactive Molecules from Natural Products 

Research Program

Dr Lau's career interests have been in Microbial Immunology and Cytokine Biology, specifically the immune responses to microbial infection including cytokine signaling and gene regulation. Prior to joining the Department in 2001, he completed a series of projects as Principal Investigator to delineate the mechanisms of HIV-induced neurotoxicity (AIDS) and the interactions between two important cytokines in antiviral and anticancer activities (Proc Natl Acad Sci USA). His group also has identified a key pathway for viruses to evade immunity and to establish chronic infection, with implications for the pathogenesis of hepatitis C and HIV (Proc Natl Acad Sci with editorial commentaries, J Biol Chem).

Over the past 8 years in HKU, he has established his research laboratory with a staff of 12-14 academic personnel including graduate students, research assistants and postdoctoral scientists. The projects are funded by external grants from Hong Kong Research Grants Council, Research Fund for the Control Infectious Disease, Innovation Technology Commission and industry funds.

Description of Research Projects in Progress:

  1. Interactions of HIV and Tuberculosis: The HIV trans-activator protein (Tat) plays an important role in the development of AIDS and its associated diseases. The primary function of Tat is to activate the HIV-LTR to enhance the replication of HIV in the infected cells. In recent reports, we showed that Tat induces cytokine production including TNF and IL-10 via the activity of an anti-viral protein kinase PKR in monocytes (FEBS Letter 2005, Immunology 2007). We are currently investigating the mechanisms of how Tat perturbs the host immune system by suppressing interferon-gamma signaling leading to immunosuppression (Blood 2009), and consequent induction of rampant mycobacterial infections.

    Tuberculosis is a major cause of morbidity and mortality in the world, particularly in developing countries. The disease is caused by Mycobacterium tuberculosis and approximately one-third of the world's population has been infected with the bacterium. Following mycobacterial infection, different branches of the host immune system are mobilized to mount defense against the pathogen. Our research interest is to elucidate the immune mechanisms that fight against mycobacterial infection (J Immunol 2005). We recently showed that glycogen synthase kinase-3 plays a role in antagonizing mycobacterial immune evasion by negatively regulating IL-10 induction (J Leukoc Biol. 2009).

  2. Avian Influenza: Together with Prof. M. Peiris (Microbiology), we have initiated a program to investigate the immunopathogenesis of avian influenza H5N1 virus infection. We previously showed that H5N1 is a potent inducer of TNF expression ( Lancet 2002, PI: Peiris ). To delineate the mechanisms involved, we have recently demonstrated that H5N1 causes super-induction of TNF via the activation of p38 MAP kinase ( J Virol 2005, J Gen Virol 2007 ). Understanding the mechanisms of cytokine dysregulation may provide new insights into the design of novel therapeutic agents. Additionally, we have used computational biology approach to identify a series of compounds capable of inhibiting influenza virus replication (J Med Chem, 2009)

Representative publications in recent five years                     

  1. * Lee DCW, Cheung CY, Law AHY, Lau AS. p38 MAPK-dependent hyper-induction of TNF-alpha expression in response to H5N1 avian influenza virus. J Virology 2005; 79:10147-54.
  2. * Cheung BK, Lee DC, Li JC, Lau YL, Lau AS. A Role for Double-Stranded RNA-activated Protein Kinase PKR in Mycobacterium-Induced Cytokine Expression. J Immunol. 2005;175:7218-7225.
  3. *Law AHY, Lee DCW, Cheung BKW, Yim HCH, Lau AS. A Role for the nonstructural protein of SARS-CoV in Chemokine Dysregulation. J Virology. 2007 Jan;81(1):416-22. Epub 2006 Oct 11.
  4. * Li JCB, Lau ASY. A role for mitogen-activated protein kinase and Ets-1 in the induction of interleukin-10 transcription by HIV-1 Tat. Immunology. 2007 Jul;121(3):337-48. Epub 2007 Mar 22.
  5. * Cheng SM, Li JC (co-first authors), Lau AS et al. HIV Tat downregulation of interferon-gamma receptor signaling pathway via the induction of SOCS.  Blood, 2009; 113:5192-201.
  6. *An J, Lee DC, Law AH, Yang CL, Poon LL, Lau AS, Jones SJ. A novel small-molecule inhibitor of the avian influenza H5N1 virus determined through computational screening against the neuraminidase. J Med Chem. 2009; 52:2667-72. (Co-corresponding authors)
  7. *Chan MM, Cheung BK, Li JC, Chan LL, Lau AS. A role for glycogen synthase kinase-3 in antagonizing mycobacterial immune evasion by negatively regulating IL-10 induction. J Leukoc Biol. 2009 Aug;86(2):283-91. Epub 2009 Apr 28.
  8. *Yim HC, Li JC, Lau JS, Lau AS. HIV-1 Tat dysregulation of lipopolysaccharide-induced cytokine responses: microbial interactions in HIV infection. AIDS. 2009 Jul 31;23(12):1473-84.
  9. * Lee DC, Yang CL, Chik SC, Li JC, Rong JH, Chan GC, Lau AS. Bioactivity-guided identification and cell signaling technology to delineate the immunomodulatory effects of Panax ginseng on human promonocytic U937 cells. J Transl Med. 2009 May 14;7:34.
  10. *Yang CL, Li JCB, Chik SC, Cheung BK, Lau AS.  Identification of the bioactive molecules in Black Cohosh and related herbs: suppressor of TNF-a activities. J Med Chem. Accepted on September 23rd 2009.    

Five representative publications beyond the recent five-year period.

  1. *Yeung MC, Chang D, Camantique R, Lau AS.  Inhibitory role of the host apoptogenic gene PKR in the establishment of persistent viral infection. Proc Natl Acad Sci 1999;96:11860-11865. Editorial Commentary
  2. *Yeung MC, Lau AS. Tumor suppressor p53 as a component of the TNF-induced and PKR-mediated apoptotic pathway in human promonocytic U937 cells.  J Biol Chem 1998;273:25198-25202
  3. *Yeung MC, Liu J, Geertsma F, Lau AS. Inhibition of HIV-1 gp120-induced apoptosis in neuroblastoma cells by an antisense oligodeoxynucleotide against p53. AIDS 1998; 12: 349-354.
  4. *Yeung MC, Liu J, Lau AS.  An essential role for the interferon-inducible, ds-RNA-activated protein kinase PKR in TNF-induced apoptosis in U937 cells. Proc National Acad Sci USA.  1996; 93:12451-12455.
  5. *Der SD, Lau AS*. Involvement of the double-stranded RNA dependent kinase PKR in interferon expression and interferon mediated antiviral activity. Proc National Acad Sci USA. 1995;92:8841-8845.

NB. * denotes A. Lau as Senior Author or PI.    

Biotechnology Patents issued/applied (out of 5):

  1. *PI: Allan S. Lau Production of Viral Vaccines in Cell Cultures.  USA Patent #6,686,190, approved    February 3, 2004. (Assignee: UCSF)
  2. *PI: Allan SY Lau. Co-I: Cindy L Yang, James CB Li, Benny KW Cheung and Stanley C Chik. Provisional USA Patent: Novel compound and uses thereof for treating inflammation and modulating immune responses.  Priority date for IP: 12 January 2009. (Assignee: HKU)
  3. *Co-PI: Jones SJ, Lau AS. Co-I: An J, Lee DC, Law AH, Poon LL. Provisional USA Patent: Identification of novel small-molecule inhibitors of the avian influenza H5N1 virus determined through computational screening. (Assignees: HKU & BCCA)

Research Presentation & Travel Awards to A. Lau trainees:

  1. * Cheung BKW#, Li JCB, Lee DCW, Lau AS. The Role of Protein Kinase PKR in the Induction of Cytokine Expression by Bacillus Calmette Guerin through NF-kB. American Society for Microbiology Annual Conference May 2003, Washington .
  2. * Li JCB# , Lee DCW, Cheung BKW and Lau AS . Mechanisms of PKR-mediates HIV Tat-induced immune response. American Society for Virology Annual Conference 2004, Montreal .
  3. * Cheung BKW#, Lee DCW and Lau AS. Signaling Mechanism of Protein Kinase PKR in the Regulation of Cytokine Expression by Bacillus Calmette Guerin. 5th Guangdong - Hong Kong Paediatrics Exchange Meeting 2004.
  4. * Leung CSK#, Li JCB, Lee DCW, Lau AS . Activation of HIV: Interactions of Tat and IL-18. American Society for Virology Annual Conference 2004, Pennsylvania .
  5. * Lee DCW#, Mok CKP , Cheung CY, Law AHY, Peiris M and Lau AS. The Paradox of H5N1 Avian Influenza Virus Infection in Primary Blood macrophages: TNF-alpha Hyper-induction and a Delay in Apoptosis. 7th World Congress on Inflammation, October 2005. Melbourne , Australia . Lee is the recipient of Second Prize Young Investigator Award.
  6. *Law AHY#, Benny KW Cheung, Davy CW Lee and Allan SY Lau. Differential Regulation of Chemokine Expression by SARS-Coronavirus Genes. The International Society for Interferon and Cytokine Research (ISICR), Shanghai, October 2005
    #Recipient of Seymour and Vivian Milstein Travel Award and 2005 Ferid Murad Award (Best Poster Award).
  7. * Yim CH#, Li JCB, Lau AS. HIV suppresses cytokine response to bacterial endotoxin. The International Conference for Cytokine Research, Vienna , August 2006. #Recipient of ISICR Travel Award.
  8. * Li JCB#, Yim CH, Lau ASY. HIV evasion of immunity via dysregulation of IL-10 expression. Hong Kong Society for Immunology Meeting, Best Abstract and Presentation Award, May 2008.
  9. * Li JCB#, Yim HCH, Lau ASY. Cellular signaling events in cytokines and sulfamethoxasole interactions. First Annual Scientific Meeting. Hong Kong Society for Paediatric Immunology and Infectious Diseases. Second Prize, Oral Presentation Award, May 2008.
  10. * Yim HCH#, Li JCB, Lau ASY. HIV-1 Tat plays a role in dysregulating lipopolysaccharide-induced cytokine expression: implications for immune defects in AIDS. First Annual Scientific Meeting. Hong Kong Society for Paediatric Immunology and Infectious Diseases. First Prize, Oral Presentation Award, May 2008.

External Competitive Grants funded as Principal Investigator in HKU:

RGC-General Research Fund: HKU# 7685/09M, HKU#7685/07M, #7594/06M, #7408/04M, #7459/03M, #7531/03M, and #7305/02M. 

Hong Kong RFCID Research Grants: #09080832, #09080512, #06060612, #05050112, and #01031052

Contact Information:

Professor Allan Lau
Dr. James Li
Secretary: Ms. Olive Yu Telephone  (852) 2855-4091 

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