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Professor, Department of Pediatrics and Child Health and Department of Immunology, University of Manitoba
Post-doctoral fellow, Dept of Pediatrics and Child Health, University of Manitoba (1989-1991)
Post-doctoral fellow, Division of Clinical Immunology, John’s Hopkins University School of Medicine (1986-1988)
M.Sc. in Immunology, Shanghai First Medical University (1979-1982)
M.D. Shanghai First Medical University (1962-1968)
1. Immune down-regulatory approaches in asthma and inflammatory bowel disease.
Since the introduction of vaccines against microbes, many infectious diseases have become well controlled. However, diseases reflecting abnormal immune responses, such as allergic asthma and inflammatory bowel disease (IBD), have increased significantly. Despite recent advances in therapy, many patients with the diseases have symptoms that are not adequately controlled. Thus, the search for innovative therapies continues.
(1) Myeloid derived suppressor cells (MDSCs) (2010-present). MDSCs are a heterogeneous population of cells that expand during cancer and, recently found, nearly all inflammatory conditions. These cells have remarkable abilities to suppress T cell responses. We have found MDSC numbers are increased in mice with allergic airway inflammation or experimental colitis, and demonstrated, for the first time, by adoptive transfer MDSCs generated in vitro from bone marrow cells could ameliorate inflammation (J Leukoc Biol 2013;94:803-11), providing pioneered data for a cell-based therapy in asthma and IBD.
(2) Cytokine vaccines (2002-present). To down-regulate excessive immune responses, we have investigated a new area of active immunization with IgE or cytokine peptide-based vaccines for the treatment of these disorders associated with cytokine dysfunction. To date, we have developed and in vivo tested vaccines against IgE, IL-4, IL-13, IL-18 and IL-12/IL-23p40 in animal models of asthma and/or colitis. Antibodies against self-IgE can be induced by IgE peptide-based vaccines, which are effective in preventing the increase of IgE and in down-regulating IgE in sensitized animals (Clin Exp Allergy 2007). Furthermore, administration of either an IL-13 or an IL-4 vaccine effectively suppresses airway allergic inflammatory responses in asthmatic mice, suggesting a novel approach for the long-term treatment of asthma (Am J Respir Cell Mol Biol 2013; Clin Exp Allergy 2012; J Am Respir Cri Care Med 2007; Allergy 2007). We have found that administration of vaccines against IL-12/IL-23p40, IL-18 or TGFβ effectively reduces colon inflammation and fibrosis in chronic experimental colitis (Vaccine 2009, 2010; Inflamm Bowel Dis 2010; Molecul Med 2011; Immunotherapy 2012, 2013). The above studies represent a novel approach to the long-term treatment of these severe, chronic, and often lifelong diseases.
(3) AMP activation protein kinase (2008 – present). We have, for the first time, examined the role of AMP-activation protein kinase (AMPK) in the downregulation of immune responses in murine colitis. Our results indicate activation of AMPK attenuates acute and chronic experimental colitis by down-regulating macrophage activation and Th1 and Th17 responses (J Pharmacol Exp Ther 2010; Biochem Pharmacol 2010), representing a promising alternative to our current treatments in IBD.
2. Mosquito allergy (1994 – present) – resulted in more than 25 papers in peer-reviewed journals including 6 papers published in JACI. My lab is now considered to be the leading facility in the world for the study of mosquito allergy at the molecular level. The following are our unique contributions:
(1) Immunological mechanisms. We studied immune mechanisms involved in mosquito allergy, discovered “Skeeter Syndrome”, reported for the first time the prevalence of mosquito allergy, the entire course of acquired sensitization and subsequent desensitization to mosquito bites, natural desensitization in humans, and mosquito bite-induced anaphylaxis, providing new information on allergy, especially on mosquito allergy.
(2) Recombinant allergens. We analysed salivary allergens and cloned, characterized, and studied the clinical relevance of 4 recombinant salivary allergens. These recombinant allergens make it possible to accurately diagnose and treat people allergic to mosquito bites.