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Dr CHAN Sau-Fong, Vera

Dr Vera Chan

Scientific Officer

email sfvchan@hku.hk
email HKU Scholars Hub
Biography

Dr Vera S.F Chan is currently an Assistant Professor in the Department of Medicine, School of Clinical Medicine and the School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong. Dr Chan obtained a B.Sc. (Hons) in Biological Science at the University of Hong Kong. With the support of the Croucher Scholarship, Dr Chan obtained her D.Phil. in Molecular Immunology and graduated from the Nuffield Department of Medicine, the Oxford University, United Kingdom. Continued with the award of the Croucher Fellowship, she received post-doctoral training at the Ontario Cancer Institute, the University of Toronto in Canada.  In 2006, she was recruited as a Lecturer at Imperial College London in UK and she re-joined HKU in 2010.

Dr Chan was initially trained to study the mechanisms of T cell tolerance and activation that lead to immunity or autoimmunity. Later, her research scope broadened to innate immunity, particularly on the role of the C-type lectin pathogen receptors DC-SIGN and L-SIGN in infectious diseases. Together with colleagues in HKU, their teams identified the genetic association as well as the protective mechanism of L-SIGN in modulating susceptibility to SARS infection.  Upon joining the Division of Rheumatology & Clinical Immunology, Department of Medicine HKU in 2010, Dr Chan continues her research in studying the immunopathology of systemic lupus erythematosus (SLE), focusing on the functional abnormalities in dendritic cells; delineation of epigenetic regulatory elements in SLE development;and the functional elucidation of CLEC16A, a novel C-type lectin-like molecule that is genetically associated with autoimmunity. Her team also involves in collaborative projects,  exploring the ‘-omics’ platforms for developing biomarkers for lupus nephritis prognosis as well as developing immunological tools for detecting circulating levels of biologics in rheumatoid arthritis patients.


Research Profile
  • C-type lectin receptors immunobiology: its role in autoimmune diseases and infection
  • cellular immuno-dysregulation in systemic lupus erythematosus (SLE)
  • development of humanized-mouse models for autoimmune diseases pathogenesis study
  • immuno-therapeutics development
Dr Vera Chan Research pictures
A. L-SIGN (red) expressing cell internalizes E.coli (green); B. Dendritic cell internalizes SARS coronaviruses (red arrow)
C-type lectin receptors (CLRs) are important sugar-binding immuno-modulatory receptors that recognize pathogens through the pathogen-associated molecular patterns (PAMPs), and are widely expressed by antigen presenting cells such as dendritic cells (DCs) -- the master cell type that orchestrates immune responses. My laboratory focuses on studying the roles of several CLRs, in particular L-SIGN, DC-SIGN and CLEC16A, in infection and autoimmunity. My previous work has delineated a unique protective mechanism mediated by homozygous L-SIGN molecules which, when compared to the heterozygous counterparts, have a higher virus binding ability that leads to subsequent proteasome-dependent viral degradation and reduces trans-infection, thereby rendering individuals less susceptible to SARS coronavirus infection (Nat Genet 2006, 38:38-46). Apart from liver sinusoidal endothelial cells, L-SIGN is also expressed by a novel subset of CD34+Oct+ lung stem/progenitor cells. These novel lung progenitor cells are susceptible to SARS coronavirus infection and support viral replication (J Exp Med 2007, 204:2529-2536), thereby serving as another viral reservoir in the lung and contribute to SARS immunopathogenesis in human. DC-SIGN is a close homologue of L-SIGN. These two CLRs bind to many pathogens in common, however, they have distinct expression pattern and thus play different role in disease pathogenesis. Together with our collaborators at Imperial College London, we have shown that dengue viruses produced by insect cells and human DCs have different glycosylation in the envelop protein and display different binding preferences for DC-SIGN and L-SIGN (J Infect Dis, 2011, 203: 1775-1783). Likely, DC-SIGN expressing skin-resident DCs may only serve as the initial site of infection by insect-produced virus but have limited contribution to subsequent virus replication during dengue infection. In another collaborative project with researchers at Kaohsiung Medical University Taiwan, we have disclosed a previously unknown immuno-modulatory mechanism mediated by HIV that through the interaction of HIV gp120 envelop protein with DC-SIGN, DCs undergo ASK-1-dependent apoptosis (PLoS Pathog, 2013, 9(1):e1003100). Findings from this study provide new approaches for developing therapeutics to prevent DC depletion in chronic HIV infection. Recently, I have extended the investigation on CLR biology in autoimmune diseases. CLRs recognize endogenous ligands that associated with damaged cells through the damaged-associated molecular patterns (DAMPs). Our recent RGC-funded research project involves the functional characterization of the novel C-type lectin domain family 16 member A (CLEC16A), which is genetically associated with a number of autoimmune disorders including systemic lupus erythematosus (SLE). Its functional implication in DC biology, in particular the effect in modulating DC interaction with other immune cells such as various T helper subsets and B cells, are being examined. The functional contribution to SLE pathogenesis is under investigation.
Another research direction of my laboratory focuses on the development of therapeutics in cancer and autoimmune diseases. Previously, together with collaborators in the Chemistry Department at HKU, we tested various novel anti- nasopharyngeal carcinoma (NPC) agents and found that gold (III) porphyrins complex was superior to cisplatin in suppressing NPC growth in an animal model (Int J Cancer 2008, 124:1971-1979). This finding reveals a promising chemotherapeutic agent that deserves further development for the treatment of advanced NPC, in particular, for cases with cisplatin-resistance. In other joint explorations to harness EBV-specific T cell responses for NPC immunotherapeutics development, we also developed several novel anti-EBV DNA vaccines, and a peptide vaccine with multiple antigenic peptide (MAP)-epitope that induce better EBV-specific T cell responses in vitro (Bioconjugate Chem 2008, 20:24–31). My laboratory is currently developing a humanized mouse model using the immunodeficient NOD-SCID-IL2RGamma chain (NSG) mutant mice, aiming to create a better pre-clinical model for studying SLE pathogenesis and for testing the in vivo effectiveness of novel vaccines and treatment modalities.

Selected Publications
  1. Chan VS, Tsang HH, Tam RC, Lu L, Lau CS. B-cell-targeted therapies in systemic lupus erythematosus. Cell Mol Immunol. 2013 10:133-42.
  2. Chen Y, Hwang SL, Chan VS, Chung NP, Wang SR, Li Z, Ma J, Lin CW, Hsieh YJ, Chang KP, Kung SS, Wu YC, Chu CW, Tai HT, Gao GF, Zheng B, Yokoyama KK, Austyn JM, Lin CL. Binding of HIV-1 gp120 to DC-SIGN promotes ASK-1-dependent activation-induced apoptosis of human dendritic cells. PLoS Pathog, 2013, 9(1):e1003100.
  3. Chan VS, Nie YJ, Shen N, Yan S, Mok MY, and Lau CS. Distinct roles of myeloid and plasmacytoid dendritic cells in systemic lupus erythematosus. Autoimmun Rev, 2012, 11: 890-7.
  4. Dejnirattisai W, Webb AI, Chan VS, Jumnainsong A, Davidson A, Mongkolsapaya J, and Screaton G. Lectin Switching During Dengue Virus Infection. J Infect Dis, 2011, 203: 1775-1783.
  5. To YF, Sun RW, Chen Y, Chan VS*, Yu WY, Tam PK, Che CM, and Lin CL. Gold(III) porphyrin complex is more potent than cisplatin in inhibiting growth of nasopharyngeal carcinoma in vitro and in vivo. Int J Cancer 2008, 124:1971-1979 (*corresponding author)
  6. Cheung WH, Chan VS, Pang HW, Wong MK, Guo ZH, Tam PK, Che CM, Lin CL, and Yu WY. Conjugation of Latent Membrane Protein (LMP)-2 Epitope to Gold Nanoparticles as Highly Immunogenic Multiple Antigenic Peptides for Induction of Epstein-Barr Virus-Specific Cytotoxic T-Lymphocyte Responses in Vitro. Bioconjugate Chem 2008, 20:24–31
  7. Chen, Y*, Chan VS*, Zheng B, Chan KY, Xu X, To YF, Huang FP, Khoo US and Lin CL. A novel subset of putative stem/progenitor CD34+Oct-4+ cells is the major target for SARS coronavirus in human lung. J Exp Med 2007, 204:2529-2536. (*equal contribution)
  8. Chan VS*, Chan KY*, Chen Y*, Poon LL, Cheung A, Zheng B, Chan KH., Mak W, Ngan HY, Xu X, Screaton G., Tam PK, Austyn J, Chan LC, Yip SP, Peiris M, Khoo US and Lin CL. Homozygous L-SIGN (CLEC4M) plays a protective role in SARS coronavirus infection. Nat Genet 2006, 38:38-46 (*equal contribution)
  9. Chan VS, Chau S, Tian L, Chen Y, Kwong SKY, Quackenbush J, Dallman M, Lamb J and Tam PKH. Sonic hedgehog promotes CD4+ lymphocyte proliferation and modulates the expression of a subset of CD28 targeted genes. Int Immunol 2006, 18:1627-1636.
  10. Chan VS, Wong C, and Ohashi PS. Calcineurin A-alpha plays an exclusive role in TCR signaling in mature but not in immature T cells. Eur J Immunol 2002, 32:1223-1229.

Research Funding
  • General Research Fund, HKRGC: The role of regulatory microRNAs in plasmacytoid dendritic cell functions in systemic lupus erythematosus immunopathogenesis, 2013-15 (Co-I).
  • Seed Fund for Basic Research, HKU: Molecular profiling of pathogenic dendritic cells development in systemic lupus erythematosus, 2012-2013 (PI).
  • General Research Fund, HKRGC: Functional characterization of the novel C-type lectin-like receptor CLEC16A and its expression association in systemic lupus erythematosus, 2011-2014 (PI).
  • Seed Fund for Basic Research, HKU: Development of a humanized mouse systemic lupus erythematosus model for studying disease pathogenesis and evaluation of therapeutic treatment efficacy, 2011-2013 (PI).
  • Hammersmith Hospital Trustees' Research Committee Grant, UK: Differentiation and development of lung stem/progenitor cells from human embryonic cell line – a model for studying pathogenesis for SARS and H5N1 infection. 2008-2009 (PI).
  • CRCG, HKU: The study of co-stimulatory function of sonic hedgehog in CD4+ T lymphocytes, 2003-2004 (Co-I).
  • SARS Fund, HKU: The effect of SARS-associated coronavirus Spike protein on immune regulation of SARS, 2003-2004 (Co-I).