• Tan, Rusung

    Titles
    Investigator Emeritus, BC Children's Hospital

    Professor Emeritus, Department of Pathology and Laboratory Medicine, University of British Columbia

    Degrees / Designations
    MD, PhD, FRCPC
    Primary Area of Research
    Secondary Area(s) of Research
    Phone
    604-875-3605
    Fax
    604-875-3777
    Lab Phone
    604-875-2450
    Assistant
    Rosemary Delnavine
    Assistant Phone
    604-875-4845
    Mailing Address

    BC Children's Hospital Research Institute
    Room A4-148
    950 West 28th Avenue
    Vancouver, BC V5Z 4H4

    Affiliate Websites
    Research Areas

    The role of cytotoxic lymphocytes (CTL and NK cells) in human disease

    Summary

    Immune white cells, such as cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, protect us from infectious diseases and cancer by killing infected or unwanted cells. Conversely, defects in the function or regulation of these cells can lead to immunodeficiency or autoimmunity. Currently we are studying the role of these cells in two diseases: type 1 diabetes and X-linked lymphoproliferative disease. In both these disorders, we have described defects in CTL and NK cells. By identifying these defects in detail we hope that we will be able to develop novel therapies for disease.

    Current Projects
    X-linked lymphoproliferative disease

    We have cloned and sequenced a novel mutation in the gene responsible for the fatal childhood disease, X-linked lymphoproliferative disease (XLP), thus resolving a longstanding mystery of unexplained male deaths in a large aboriginal family from northern Canada. The presence of the mutation in this extended family allows us to study the specific role of the lymphocyte cell protein, SLAM-associated protein (SAP) in human immunity to viruses and tumours. In particular, we are investigating the role of SAP in the cellular and molecular dysfunction of cytotoxic T lymphocytes and natural killer cells and the relationship between these abnormalities and the clinical phenotype of disease.

    Autoimmunity in type 1 diabetes
    Type 1 (juvenile-onset) diabetes mellitus arises from a T-cell-mediated autoimmune process directed against pancreatic beta cells in both humans and non-obese diabetic (NOD) mice. The destruction of beta cells is mediated by CD8+ cytotoxic T lymphocytes (CTL). Using MHC Class 1 tetrameric complexes to detect and determine the frequency of autoreactive CTL in NOD mice we have developed a predictive algorithm for disease. In collaboration with Drs. Bruce Verchere and Dina Panagiotopoulos we are hoping to extend these findings to humans through the identification of human MHC class I restricted epitopes. The laboratory is also studying several different areas of the pathogenesis of type 1 diabetes including the role of autoreactive CTL and the role of natural killer cells.

    Medical microbiology, virology and infection control (clinical)
    The medical microbiology laboratory in the Department of Pathology & Laboratory Medicine at BC Children's Hospital (BCCH) is a leader in the development of molecular diagnostic assays for pediatric infectious diseases. For example, molecular assays have been developed for human herpesvirus 6 (HHV-6), enteroviruses and Epstein-Barr virus, for the diagnosis and typing of Neisseria meningitidis (meningococcus) and for novel agents such as human metapneumovirus. The laboratory is continually adapting and developing new real-time (Taqman) and rapid Smart Cycler PCR diagnostics for a variety of bacterial and viral pathogens.  In addition the laboratory is engaged in changing the primary care management of common respiratory illnesses by providing a VIral RAPid testing program (VIRAP) that allows for the rapid (<4 hour) diagnosis of common respiratory pathogens.

    Selected Publications

    B Chung, K Tsai, L Allan, D Zheng, J Nie, C Biggs, M Hasan, F Kozak, P van den Elzen, J Priatel and R Tan. Innate immune control of EBV-infected B cells by invariant natural killer T cells. Blood; doi:10.1182/blood-2013-01-480665.

    H. Qin, I-F. Lee, C. Panagiotopoulos, X. Wang, A. Chu, PJ. Utz, J. Priatel and R. Tan. Natural killer cells from subjects with type 1 diabetes have defects in NKG2D-dependent function and signaling. Diabetes. 2011;60:857-866.


    A. Marwaha, S. Crome, C. Panagiotopoulos, K. Berg, H. Qin, Q. Ouyang, L. Xu, J. Priatel, M. Levings and R. Tan. Cutting Edge: Increased IL-17 Secreting T Cells In Children With New-Onset Type 1 Diabetes. Journal of Immunology. 2010;185:3814-3818.

    L. Allen, K. Hoefl, D. Zheng, B. Chung, F. Kozak, R. Tan and P. van den Elzen. Apolipoprotein mediated lipid antigen presentation in B cells provides a pathway for innate help by NKT cells. Blood. 2009;114:2411-6.

    Q. Ouyang, N. Standifer, H. Qin, P. Gottlieb, C.B. Verchere, G. Nepom, R. Tan*, and C. Panagiotopoulos. Recognition of HLA class I-restricted beta-cell epitopes in type 1 diabetes. Diabetes. 2006; 55:3068-3074

    B. Chung, A. Aoukaty, J. Dutz, C. Terhorst and R. Tan. SLAM-associated protein controls NKT cells functions. Cutting Edge: Journal of Immunology. 2005; 174:3153.

    C. Panagiotopoulos, H. Qin H, R. Tan* and C.B. Verchere*. Identification of a beta cell specific MHC class I restricted epitope in type 1 diabetes. Diabetes. 2003; 52:2647-2651.

    A. Aoukaty and R. Tan. Association of the XLP gene product SAP/SH2D1A with 2B4, a natural killer cell activating molecule, is dependent on phosphoinositide 3-kinase. Journal of Biological Chemistry.2002;277:13331-7.

    J. Trudeau, C. Kelly-Smith, C.B. Verchere, J. Dutz, J. Elliott, D. Finegood, P. Santamaria and R. Tan. Prediction of spontaneous autoimmune diabetes by quantification of autoreactive T cells in peripheral blood. Journal of Clinical Investigation. 2003; 111(2): 217–223.

    J. Dutz, X. Wang, L. Benoit, A. Junker, D. De Sa and R. Tan. Lymphocytic vasculitis in X-linked lymphoproliferative disease. Blood 2001; 97:95-100.

    L. Benoit, X. Wang, J. Dutz and R. Tan. Defective natural killer cell activation in X-linked lymphoproliferative disease. Cutting Edge: Journal of Immunology. 2000; 165-3549.

    Grants

    Honours & Awards

    Michael Smith Foundation Senior Scholar 2006-

    Most Valuable Player, Department of Pathology & Laboratory Medicine, University of British Columbia - 2009

    Green College Faculty Member, 2005-

    Peter Wall Institute of Advanced Studies Early Career Scholar, University of British Columbia – 2003-2004

    Research & Discovery Award, Department of Pathology & Laboratory Medicine, University of British Columbia - 2002

    Lotte Strauss Prize, Society for Pediatric Pathology - 2001

    Samuel F. McLaughlin Fellowship in Medicine - 1995-1997
    Research Group Members