• Turvey, Stuart

    Titles

    Senior Clinician Scientist, CFRI
    Director, Clinical Research, CFRI
    Aubrey J. Tingle Professor of Pediatric Immunology
    Associate Professor, Division of Infectious and Immunological Diseases, Department of Pediatrics, University of British Columbia

    Degrees / Designations
    MBBS, DPhil, FRCPC
    Primary Area of Research
    Immunity in Health & Disease
    Secondary Area(s) of Research
    Phone
    604-875-2345 ext. 5094
    Fax
    604-875-2226
    Lab Phone
    604-875-3131
    Assistant
    Valerie Tolsma (Administrative Assistant), Kate Del Bel (Lab Manager)
    Assistant Phone
    604-875-3130 (Valerie) or 604-875-3131 (Kate)
    Mailing Address
    Child & Family Research Institute
    A5-145, 950 West 28th Avenue
    Vancouver, BC V5Z 4H4
    Affiliate Websites
    Research Areas
    • Innate immunity
    • Host defense
    • Primary immunodeficiency diseases (PIDs)
    • Role of Toll-like receptors in human disease
    • Airway inflammation in cystic fibrosis
    • Asthma and allergic disease
    Summary

    Despite much effort, we know little about how the healthy child is protected from infectious disease, and even less about why some children develop inflammatory disorders. Why do some healthy children succumb to overwhelming bacterial infection, while others either survive infection or do not become infected at all? Why do some children suffer crippling juvenile arthritis or life-threatening asthma?

    My research program is translational, interdisciplinary and unique in its focus on understanding the role of innate immunity in infectious and inflammatory diseases of childhood. Starting with a population of children with a defined infectious or inflammatory disease phenotype (e.g., undue susceptibility to infection, juvenile idiopathic arthritis), I aim to determine the underlying cellular, molecular and genetic abnormalities responsible for the disease through detailed immunological, genomic and proteomic analysis. The new knowledge generated by this approach will aid diagnosis, elucidate mechanisms of disease pathogenesis and, ultimately, identify novel targets for anti-inflammatory and anti-infectious therapeutic agents.

    Current Projects

    Genetics of Susceptibility to Childhood Infection

    Until very recently, clinical immunologists have focused most attention on patients with a ‘noisy clinical phenotype’—multiple, severe and recurrent infections. Indeed, the origin of primary immunodeficiencies is generally attributed to Bruton’s 1952 description of X-linked agammaglobulinemia in a boy whose repeated pneumococcal infections demanded clinical attention.

    Today, enhanced understanding of human immunity combined with ever more sophisticated tools to dissect the immune response have allowed clinical immunologists to look beyond these "noisy", severely immunocompromised patients to individuals with less obvious immune defects. We have entered the era of "subtle" primary immunodeficiencies that will begin to precipitate a fundamental change and expansion of the focus of clinical immunologists.

    My lab is involved in searching for subtle genetic immune defects in apparently healthy children who developed serious infections, including invasive pneumococcal infection and severe respiratory syncytial virus infection. This journey towards subtlety is anticipated to translate into better care for our patients through improved diagnosis, combined with tailored treatment and targeted prophylaxis.

    Innate Immunity and Lung Inflammation in Cystic Fibrosis

    Cystic fibrosis (CF) is the most common, deadly genetic disease affecting young Canadians. Even today, only half of the people living with CF will survive beyond their mid-thirties. New treatments for CF are critically needed.

    Lung disease is the major life-limiting factor for people living with CF. Lung injury in CF occurs through a vicious cycle of airway blockage, infection and inflammation. Current CF treatments rely upon physiotherapy to reduce airway blockage and antibiotics to treat the infections, but these treatments do not specifically deal with inflammation. New treatments to simultaneously target airway inflammation are likely to provide substantial additional benefits in improving the quality and length of life for those with CF.

    Through synergistic studies harnessing the power of cell biology, chemistry and functional genomics, we are working to identify optimal "druggable" targets responsible for CF airway inflammation and to discover novel anti-inflammatory drugs. Ultimately, these experiments are designed to develop new therapies for safely reducing lung inflammation and improving the quality and length of life of people with CF.

    Canadian Healthy Infant Longitudinal Development (CHILD) Study

    Over the past 30 years there has been an increasing concern about the effects of environment on health. In particular, since infants spend the majority of their time indoors, there is intense interest in the impact indoor pollution has on the health of our children. Our indoor environment has become a public health priority as growing evidence suggests that unseen environmental contaminants in our living spaces may have important effects on children's health and development.

    The Canadian Healthy Infant Longitudinal Development (CHILD) Study is a multicentre, multidisciplinary, longitudinal, population-based birth-cohort study of 5,000 children enrolled "pre-birth" and followed for five years (www.canadianchildstudy.ca). The main purpose of this study is to determine what aspects of the environment interact with genetic factors to affect children’s health and development. I am a co-principal investigator for the CHILD study and I lead the Vancouver study site.

    Selected Publications

    Sbihi H, Brook JR, Allen RW, Curran JH, Dell S, Mandhane P, Scott JA, Sears MR, Subbarao P, Takaro TK, Turvey SE, Wheeler AJ, Brauer M (2013). A new exposure metric for traffic-related air pollution? an analysis of determinants of hopanes in settled indoor house dust. Environ Health 12(1):48. PMID: 23782977

    Cho P, Gelinas L, Corbett NP, Tebbutt SJ, Turvey SE, Fortuno ES 3rd, Kollmann TR (2013). Association of common single-nucleotide polymorphisms in innate immune genes with differences in TLR-induced cytokine production in neonates. Genes Immun 14(4):199-211. PMID: 23466493

    Hsu KJ, Turvey SE (2013). Functional analysis of the impact of ORMDL3 expression on inflammation and activation of the unfolded protein response in human airway epithelial cells. Allergy Asthma Clin Immunol 9(1):4. PMID:23369242

    Ali S, Hirschfeld AF, Mayer ML, Fortuno ES 3rd, Corbett N, Kaplan M, Wang S, Schneiderman J, Fjell CD, Yan J, Akhabir L, Aminuddin F, Marr N, Lacaze-Masmonteil T, Hegele RG, Becker A, Chan-Yeung M, Hancock REW, Kollmann TR, Daley D, Sandford AJ, Lavoie PM, Turvey SE (2013). Functional genetic variation in NFKBIA and susceptibility to childhood asthma, bronchiolitis and bronchopulmonary dysplasia. J Immunol 190(8):3949-58. PMID: 23487427

    Mayer ML, Blohmke CJ, Falsafi R, Fjell CD, Madera L, Turvey SE, Hancock REW (2013). Rescue of dysfunctional autophagy attenuates hyerinflammatory responses from cystic fibrosis cells. J Immunol 190(3):1227-38. PMID:2364659

    You D, Marr N, Saravia J, Shrestha B, Lee GI, Turvey SE, Brombacher F, Herbert D, Cormier SA (2013). IL-4Rα on CD4+ T cells plays a pathogenic role in respiratory syncytial virus reinfection in mice infected initially as neonates. J Leukoc Biol 93(6):933-42. PMID:23543769

    Yang H, Zhou Y, Fung SY, Wu L, Tsai K, Tan R, Turvey SE, Machuca T, de Perrot M, Waddell T, Liu M (2013). Amino acid structure determines the immune responses generated by peptide-gold nanoparticle hybrids. Particle & Particle Systems Characterization. (In press.)

    Marr N, Turvey SE (2012).  Role of human TLR4 in respiratory syncytial virus-induced NF-κB activation, viral entry and replication. Innate Immunity 0(0):1-10. PMID: 22535679

    Lavoie PM, Ladd M, Hirschfeld AF, Huusko J, Mahlman M, Speert DP, Hallman M, Lacaze-Masmonteil T, Turvey SE (2012). Influence of Common Non-Synonymous Toll-like Receptor 4 Polymorphisms on Bronchopulmonary Dysplasia and Prematurity in Human Infants. PLoS ONE 7(2):e31351. PMID: PMC3279371

    Turvey SE, Leo SH, Boos A, Deans GD, Prendiville J, Crawford RI, Senger C, Conley ME, Tilley P, Junker A, Janz L, Azana R, Hoang L, Morton TL (2012). Successful Approach to Treatment of Helicobacter bilis Infection in X-Linked Agammaglobulinemia. J Clin Immunology 32(6):1404-8. PMID: 22843217

    Tang A, Sharma A, Jen R, Hirschfeld AF, Chilvers MA, Lavoie PM, Turvey SE (2012) Inflammasome-Mediated IL-1β Production in Humans with Cystic Fibrosis. PLoS ONE 7(5):e37689. PMID: 22649552

    Blohmke CJ, Mayer ML, Tang AC, Hirschfeld AF, Fjell CD, Sze MA, Falsafi R, Wang S, Hsu K, Chilvers MA, Hogg JC, Hancock REW, Turvey SE (2012). Atypical activation of the unfolded protein response in cystic fibrosis airway cells contributes to p38 MAPK-mediated innate immune responses. J Immunol 189(11):5467-75. PMID: 23105139

    Gaglia JL, Guimaraes AR, Harisinghani M, Turvey SE, Jackson R, Benoist C, Mathis D, Weissleder R. (2011). Non-invasive imaging of pancreatic islet inflammation in type-1 diabetes patients. J Clin Invest 121(1):442-5. PMID: 21123946

    Mayer ML, Sheridan JS, Blohmke CJ, Turvey SE, Hancock REW (2011). The Pseudomonas aeruginosa autoinducer 3O-C12 homoserine lactone provokes hyperinflammatory responses from cystic fibrosis airway epithelial cells in a calcium-dependent manner. PLoS ONE 6(1):e16246. PMID: 21305014

    Blohmke CJ, Park J, Hirschfeld AF, Victor RE, Schneiderman J, Stefanowicz D, Chilvers MA, Durie PR, Corey M, Zielenski J, Dorfman R, Sandford AJ, Daley D, Turvey SE (2010). Toll-like receptor 5 is an anti-inflammatory target and modifier gene in cystic fibrosis. J Immunol 185(12):7731-8. PMID: 21068401

    Douville RN, Lissitsyn Y, Hirschfeld AF, Becker A, Kozyrskyj A, Liem J, Bastien N, Li Y, Victor RE, Sekhon M, Turvey SE*, HayGlass KT* (2010). Toll-Like Receptor 4 Asp299Gly Polymorphism: No Impact on Human Immune Responsiveness to Lipopolysaccharide and Respiratory Syncytial Virus. PLoS ONE 5(8):e12087. (*co-senior and co-corresponding authors). PMID: 20711470

    Morishita K, Petty R, Cairns R, Bolaria R, Cabral D, Turvey S (2010). Serious musculoskeletal infections in children receiving anti-tumor necrosis factor-alpha therapy: a case series. Clin Rheumatol 29(6):677-81. PMID: 20383549

    Turvey SE, Broide DH (2010). Innate immunity. J Allergy Clin Immunol.125(2 Suppl 2):S24-32. PMID: 19932920

    Rzemieniak SE, Hirschfeld AF, Victor RE, Chilvers MA, Zheng D, van den Elzen P, Turvey SE (2010). Acidification-dependent activation of CD1d-restricted natural killer T cell is intact in cystic fibrosis. Immunology 130(2):288-95. PMID: 20102408

    Turvey SE, Bonilla FA, Junker AK (2009). Primary Immunodeficiency Diseases: A Practical Guide for Clinicians. Postgrad Med J 85(1010):660-6). PMID: 20075404

    Cuvelier GDE, Schultz KR, Davis J, Hirschfeld AF, Junker AK, Tan R, Turvey SE (2009). Optimizing Outcomes of Hematopoietic Stem Cell Transplantation for Severe Combined Immunodeficiency. Clin Immunol 131(2):179-88. PMID: 19217351

    Subbarao P, Becker A, Brook JR, Daley D, Mandhane PJ, Miller G, Turvey SE, Sears MR on behalf of the CHILD study investigators (2009). Epidemiology of Asthma: Risk Factors for Development. Expert Review of Clinical Immunology, 5(1): 77-95. PMID: 20476901

    Blohmke CJ, Victor RE, Hirschfeld AF, Elias IM, Hancock DG, Lane CR, Davidson AG, Wilcox PG, Smith KD, Overhage J, Hancock RE, Turvey SE (2008). Innate immunity mediated by TLR5 as a novel antiinflammatory target for cystic fibrosis lung disease. Journal of Immunology; 180(11):7764-7773. PMID: 18490781

    Burgess TST, Hirschfeld AF, Tyrrell GJ, Bettinger JA, Turvey SE (2008). Commonly Invasive Serotypes of Streptococcus pneumoniae Trigger a Reduced Innate Immune Response Compared with Serotypes Rarely Responsible for Invasive Infection. FEMS Immunol Med Microbiol. 53(1): 136-9. PMID: 18248437

    Afforder, N, Turvey SE (2008). Book Review “Toxic Exposures: Contested Illnesses and the Environmental Health Movement”, by Phil Brown. Osgoode Hall Law Journal, 46(2): 427-433.

    Turvey SE, Speert DP (2007) Recurrent Systemic Pneumococcal Disease and IRAK4-Deficiency. Pediatric Infectious Disease Journal 26:1074. PMID: 17984826

    Paulus SC, Hirschfeld AF, Victor RE, Thomas E, Brunstein J, Turvey SE (2007). Common Human Toll-like Receptor 4 Polymorphisms—Role in Susceptibility to Respiratory Syncytial Virus Infection and Functional Immunological Relevance. Clinical Immunology; 123(3):252-257. PMID: 17449325

    Hirschfeld AF, Bettinger JA, Victor RE, Davidson DJ, Currie AJ, Ansermino JM, Scheifele DW, Orange JS, Turvey SE (2007). Prevalence of Toll-like Receptor Signalling Defects in Apparently Healthy Children Who Developed Invasive Pneumococcal Infection. Clinical Immunology; 122(3):271-278. PMID: 17157070

    Hirschfeld AF, Jiang R, Robinson WP, McFadden DE, Turvey SE. (2007) Toll-Like Receptor 4 Polymorphisms and Idiopathic Chromosomally-Normal Miscarriage. Human Reproduction, 22:440-443. PMID: 16982657

    Cohen L, Hirschfeld AF, Junker AK, Davis J, Turvey SE (2006). Detection of a novel nonsense mutation in the interleukin 2 receptor, gamma gene causing X-linked severe combined immunodeficiency. Annals of Allergy, Asthma and Immunology, 96(4):632. PMID: 16680939

    Nishio J, Gaglia J, Turvey SE, Campbell P, Benoist C, Mathis D (2006). Islet recovery rather than splenocyte transdifferentiation in the reversal of type 1 diabetes. Science, 311:1775-8. PMID: 16556845

    Turvey SE, Hawn TR (2006). Towards Subtlety: Understanding the Role of Toll-like Receptor Signaling in Susceptibility to Human Infections. Clinical Immunology, 120(1):1-9. PMID: 16563867

    Turvey SE, Swart E; Denis MC, Mahmood U, Benoist C, Weissleder R, Mathis D. (2005). Non-invasive imaging of type 1 diabetes and its reversal. Journal of Clinical Investigation, 115:2454-2461.

    Grants


    Honours & Awards

    Canadian Society of Allergy and Clinical Immunology, Award for Research in Immunology 2013

    Aubrey J. Tingle Professorship in Pediatric Immunology, 2012-Present

    Career Investigator Scholar Award, Michael Smith Foundation for Health Research, 2011-19.

    The Chaim Roifman Scholar Award, Canadian Immunodeficiency Society. 2009-10.

    Career Development Award, Canadian Child Health Clinician-Scientist Program. 2006-10.

    Ivory Tower Award for Teaching Distinction, UBC Department of Pediatrics. 2006.

    Millenium Trainee Award, Clinical Immunology Society. 2004.

    Thomas Percival Junior Research Fellowship, Harris Manchester College, Oxford. 1997-99.

    Rhodes Scholarship. 1995-99.

    P.O. Bishop University Medal in Physiology, The University of Sydney. 1993.

    Research Group Members

    Kate Del Bel – Lab Manager
    Nico Marr – Research Associate
    Shan-Yu (Shane) Fung – Research Associate
    Hong Yang – Research Associate
    Sarah Kam – Research Technician
    Anthony Tang – Graduate Student
    Leah Thomas – Graduate Student
    Angie Lam – COOP Student
    Tina Wang – Summer Student
    Shirley Wang – Undergraduate Student
    Mary Ann Mauro – Senior Clinical Research Coordinator, CHILD study
    Maureen Campbell – Financial Manager, CHILD study
    Linda Warner – Research Nurse, CHILD study
    Susan Menzies – Clinical Research Assistant, CHILD study
    Ghazal Assadian – Clinical Research Assistant, CHILD study
    Claire Lepine – Clinical Research Assistant, CHILD study
    Robbie Mamonluk – Clinical Research Assistant, CHILD study