• Turvey, Stuart

    Titles

    Investigator, BC Children's Hospital
    Aubrey J. Tingle Professor of Pediatric Immunology
    Professor, Division of Allergy and Immunology, Department of Pediatrics, University of British Columbia

    Degrees / Designations
    MBBS, DPhil, FRCPC
    Primary Area of Research
    Healthy Starts
    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 (Research Manager)
    Assistant Phone
    604-875-3130 (Valerie) or 604-875-3131 (Kate)
    Mailing Address

    BC Children's Hospital Research Institute
    Room A5-144
    950 West 28th Avenue
    Vancouver, BC V5Z 4H4

    Affiliate Websites
    Research Areas
    • Precision medicine
    • Primary immunodeficiency diseases (PIDs)
    • Role of Toll-like receptors in human disease
    • Airway inflammation in cystic fibrosis
    • Early life origins of 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, asthma), 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

    Harnessing the power of genomics to diagnose, treat and prevent pediatric immune disorders

    Primary immunodeficiency diseases (PIDs) are a group of genetic disorders in which parts of the immune system are missing or dysfunctional. PIDs interfere with essential protective immune functions, greatly enhancing susceptibility to infections, autoimmunity, inflammation, and certain malignancies. The study of PIDs has played a critical role in expanding our understanding of the immune system and the development of treatment strategies that have applications far beyond PIDs. Despite our growing understanding of PIDs, many cases remain undiagnosed. My lab uses the power of genomics, including next-generation sequencing (NGS) technology, to discover the cause of novel PIDs, to accelerate diagnosis, to define target treatments, and to improve outcomes for children and their families.

    Early-life origins of asthma and allergic disease

    Asthma is a chronic inflammatory disease of the airways that typically begins in childhood. In Canada, more than 8% of people (~2.4 million in 2014) have been diagnosed with asthma. The underlying cause of asthma is a complex product of genetic and environmental factors; however research suggests that early life exposure to microbes alters immune system priming to increase susceptibility to asthma and allergic diseases. My lab aims to identify key compositional differences in the early-life gut microbiome, and metabolome between children who develop asthma and those who remain healthy, which can ultimately be targeted to predict and prevent asthma.

    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

    For the latest publications, please visit Dr. Turvey’s ORCID profile.

    Lu HY, Sharma M, Biggs C, Huang Y, Shopsowitz KE, Frosk P, Priatel JJ, Rubin TS, Turvey SE (2018). The importance of functional validation after next generation sequencing: evaluation of a novel CARD11 variant. Pediatr Allergy Immunol. PMID: 29808493

    Tang AC, Rahavi SM, Fung SY, Lu HY, Yang H, Lim CJ, Reid GS, Turvey SE (2018). Combination therapy with proteasome inhibitors and TLR agonists enhances tumour cell death and IL-1β production. Cell Death & Disease 9:162. PMID: 29415982

    Biggs CM, Haddad E, Issekutz TB, Roifman CM, Turvey SE (2017). Newborn screening for severe combined immunodeficiency: a primer for clinicians. CMAJ 189:E1551-1557. PMID: 29255099

    Arrieta MC, Arévalo A, Stiemsma L, Dimitriu P, Chico ME, Loor S, Vaca M, Boutin RCT, Morien E, Jin M, Turvey SE, Walter J, Parfrey LW, Cooper PJ, Finlay B (2017). Associations between infant fungal and bacterial dysbiosis and childhood atopic wheeze in a nonindustrialized setting. J Allergy Clin Immunol. PMID:29241587

    Yang H, Fung SY, Bao A, Li Q, Turvey SE (2017). Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-Like Receptor Signaling. J Vis Exp:125, e56075. PMID: 28784964

    Biggs CM, Lu HY, Turvey SE (2017). Monogenic immune disorders and severe atopic disease. Nature Genetics 49: 1162-1163. PMID: 28747751

    Del Bel KL, Ragotte RJ^, Saferali A, Lee S, Vercauteren SM, Mostafavi SA, Schreiber RA, Prendiville JS, Phang MS, Halparin J, Au N, Dean JM, Priatel JJ, Jewels E, Junker AK, Rogers PC, Seear M, McKinnon ML*, Turvey SE* (2017). JAK1 gain-of-function causes an autosomal dominant immune dysregulatory and hypereosinophilic syndrome. J Allergy Clin Immunol 139(6):2016-2020 ^These authors contributed equally to this paper. *Co-corresponding authors. PMID:28111307

    Ragotte RJ, Dhanrajani A, Pleydell-Pearce J, Del Bel KL, Tarailo-Graovac M, van Karnebeek C, Terry J, Senger C, McKinnon ML, Seear M, Prendiville JS, Tucker LB, Houghton K, Cabral DA, Guzman J, Petty RE, Brown KL, Tekano J, Wu J, Morishita KA, Turvey SE (2017). The importance of considering monogenic causes of autoimmunity: A somatic mutation in KRAS causing pediatric Rosai-Dorfman syndrome and systemic lupus erythematosus. Clin Immunol 175:143-146 ^These authors contributed equally to this paper. *Co-senior and co-corresponding authors. PMID: 28043923

    Stiemsma LT, Turvey SE (2017). Asthma and the microbiome: Defining the critical window in early life. Allergy, Asthma Clin Immunol 6;13:3. PMID:28077917

    Marwaha AK, Panagiotopoulos C, Biggs CM, Staiger S, Del Bel KL, Hirschfeld AF, Priatel JJ, Turvey SE, Tan R (2017). Pre-diagnostic genotyping identifies T1D subjects with impaired Treg IL-2 signaling and an elevated proportion of FOXP3+IL-17+ cells. Genes Immun 18(1): 15-21. PMID: 28053319

    Yang H, Kozicky L, Saferali A, Fung SY, Afacan N, Cai B, Falsafi R, Gill E, Liu M, Kollmann TR, Hancock RE, Sly LM, Turvey SE (2016). Endosomal pH modulation by peptide-gold nanoparticle hybrids enables potent anti-inflammatory activity in phagocytic immune cells. Biomaterials 111:90-102. PMID: 27728817

    Stiemsma LT, Arrieta MC, Dimitriu PA, Cheng J, Thorson L, Lefebvre DL, Azad MB, Subbarao P, Mandhane P, Becker A, Sears MR, Kollmann TR; Canadian Healthy Infant Longitudinal Development (CHILD) Study Investigators., Mohn WW, Finlay BB, Turvey SE (2016). Shifts in Lachnospira and Cloistridum sp. in the 3-month stool microbiome are associated with preschool age asthma. Clin Sci 130(23):2199-2207. PMID: 27634868

    Concepcioin AR, Vaeth M, Wagner LE 2nd, Eckstein M, Hecht L, Yang J, Crottes D, Seidl M, Shin HP, Weidinger C, Cameron S, Turvey SE, Issekutz T, Meyts I, Lacruz RS, Cuk M, Yule DI, Feske S (2016). Store-operated Ca2+-activated chloride channels and eccrine sweat gland function. J Clin Invest 126(11):4303-4318. PMID: 27721237

    Tang AC, Saferali A, He G, Sandford AJ, Strug LJ, Turvey SE (2016). Endoplasmic reticulum stress regulates chemokine production in cystic fibrosis airways cells through STAT3 modulation. J Infect Dis. 215(2):293-302. PMID: 27799352

    Rozmus J, McDonald R, Fung SY, Del Bel KL, Roden J, Senger C, Schultz KR, McKinnon ML, Davis J, Turvey SE (2016). Successful clinical treatment and functional immunological normalization of human MALT1 deficiency following hematopoietic stem cell transplantation. Clin Immunol. 168:1-5. PMID: 27109639

    Tarailo-Graovac M, Shyr C, Ross CJ, Horvath GA, Salvarinova R, Ye XC, Zhang LH, Bhavsar AP, Lee JJ, Drögemöller BI, Abdelsayed M, Alfadhel M, Armstrong L, Baumgartner MR, Burda P, Connolly MB, Cameron J, Demos M, Dewan T, Dionne J, Evans AM, Friedman JM, Garber I, Lewis S, Ling J, Mandal R, Mattman A, McKinnon M, Michoulas A, Metzger D, Ogunbayo OA, Rakic B, Rozmus J, Ruben P, Sayson B, Santra S, Schultz KR, Selby K, Shekel P, Sirrs S, Skrypnyk C, Superti-Furga A, Turvey SE, Van Allen MI, Wishart D, Wu J, Wu J, Zafeiriou D, Kluijtmans L, Wevers RA, Eydoux P, Lehman AM, Vallance H, Stockler-Ipsiroglu S, Sinclair G, Wasserman WW, van Karnebeek CD (2016). Exome sequencing and the management of neurometabolic disorders. N Engl J Med. 374(23):2246-55. PMID:27276562

    Arrieta MC^, Stiemsma LT^, Dimitriu PA, Thorson L, Russell S, Yurist-Doutsch S, Kuzeljevic B, Gold MJ, Lefebvre DL, Subbarao P, Mandhane P, Becker A, McNagny KM, Sears MR, Kollmann T, the CHILD Study Investigators, Mohn, WM, Turvey SE*, Finlay BB* (2015). Early infancy microbial and metabolic alterations impact risk of childhood asthma. Sci Transl Med 7(307):307ra152. ^These authors contributed equally to this paper. *Co-senior and co-corresponding authors. PMID: 26424567

    Grazioli S, Hamilton SJ, McKinnon ML, Del Bel KL, Hoang L, Cook VE, Hildebrand KJ, Junker AK, Turvey SE. (2015). IRAK-4 deficiency as a cause for familial fatal invasive infection by Streptococcus pneumoniae. Clin Immunol 163:14-16. PMID: 26698383

    Klein T^, Fung SY^, Renner F, Blank MA, Dufour A, Kang S, Bolger-Munro M, Scurll JM, Priatel JJ, Schweigler P, Melkko S, Gold MR, Viner RI, Régnier CH, Turvey SE*, Overall CM*. (2015). The paracaspase MALT1 cleaves HOIL1 reducing linear ubiquitination by LUBAC to dampen lymphocyte NF-κB signalling. Nat Commun 6:8777 ^These authors contributed equally to this paper. *Co-senior and co-corresponding authors. PMID: 26525107

    Lavoie PM, Solimano A, Taylor R, Kwan E, Claydon J, Turvey SE, Marr N (2015). Outcomes of respiratory syncytial virus immunoprophylaxis in infants using an abbreviated dosing regimen of palivizumab. JAMA Pediatr 28:1-2. PMID: 26720836

    Ngoh EN, Weisser SB, Lo Y, Kozicky LK, Jen R, Brugger HK, Menzies SC, McLarren KW, Nackiewicz D, van Rooijen N, Jacobson K, Ehses JA, Turvey SE, Sly LM (2015). Activity of SHIP, Which Prevents Expression of Interleukin-1β, is Reduced in Patients with Crohn’s Disease. Gastroenterology. PMID: 26481854

    Ngoh EN, Brugger HK, Monajemi M, Menzies SC, Hirschfeld AF, Del Bel KL, Jacobson K, Lavoie PM, Turvey SE, Sly LM (2015). The Crohn’s disease-associated polymorphism in ATG16L1 (rs2241880) reduces SHIP gene expression and activity in human subjects. Genes Immun 16(7):452-61. PMID: 26226011

    Yang H, Fung SY, Xu S, Sutherland DP, Kollmann TR, Liu M, Turvey SE (2015). Amino Acid-Dependent Attenuation of Toll-like Receptor Signaling by Peptide-Gold Nanoparticle Hybrids. ACS Nano 9(7):6774-84. PMID: 26083966

    Bhullar K, Zarepour M, Yu H, Yang H, Croxen M, Stahl M, Finlay BB, Turvey SE, Vallance BA (2015). The serine protease autotransporter Pic modulates Citrobacter rodentium pathogenesis and its innate recognition by the host. Infect Immun 83(7):2636-50. PMID: 25895966

    Sbihi H, Allen RW, Becker A, Brook JR, Mandhane P, Scott JA, Sears MR, Subbarao P, Takaro TK, Turvey SE, Brauer M (2015). Perinatal Exposure to Traffic-Related Air Pollution and Atopy at 1 Year of Age in a Multi-Center Canadian Birth Cohort Study. Environ Health Perspect 123(9):902-8. PMID: 25826816

    Sharma AA, Jen R, Kan B, Sharma A, Marchant E, Tang A, Gadawski I, Senger C, Skoll A, Turvey SE, Sly LM, Côté HC, Lavoie PM (2015). Impaired NLRP3 inflammasome activity during fetal development regulates IL-1β production in human monocytes. Eur J Immunol 45(1):238-49. PMID: 25311115

    Moraes TJ, Lefebvre DL, Chooniedass R, Becker AB, Brook JR, Denburg J, HayGlass KT, Hegele RG, Kollmann TR, Macri J, Mandhane PJ, Scott JA, Subbarao P, Takaro TK, Turvey SE, Duncan JD, Sears MR, Befus AD and the CHILD Study Investigators (2015). The Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort study: Biological samples and biobanking. Paediatr Perinat Epidemiol 29(1):84-92. PMID: 25405552

    Lu W, Zhang Y, McDonald DO, Jing H, Carroll B, Robertson N, Zhang Q, Griffin H, Sanderson S, Lakey JH, Morgan NV, Reynard LN, Zheng L, Murdock HM, Turvey SE, Hackett SJ, Prestidge T, Hall JM, Cant AJ, Matthews HF, Koref MF, Simon AK, Korolchuk VI, Lenardo MJ, Hambleton S, Su HC (2014). Dual proteolytic pathways govern glycolysis and immune competence. Cell 159(7):1578-90. PMID: 25525876

    Tang AC, Turvey SE, Alves MP, Regamey N,  Tümmer B, Hartl D (2014). Current Concepts: host-pathogen interactions in cystic fibrosis airways disease. Eur Respir Rev 23(133):320-32. PMID: 25176968

    Turvey SE, Durandy A, Fischer A, Fung SY, Geha RS, Gewies A, Giese T, Greil J, Keller B, McKinnon ML, Neven B, Rozmus J, Ruland J, Snow AL, Stepensky P, Warnatz K (2014). The CARD11-BCL10-MALT1 (CBM) signalosome complex: Stepping into the limelight of human primary immunodeficiency. J Allergy Clin Immunol 134(2):276-84. PMID: 25087226

    Grazioli S, Bennett M, Hildebrand KJ, Vallance H, Turvey SE, Junker AK (2014). Limitation of TREC-based newborn screening for ZAP70 Severe Combined Immunodeficiency. Clin Immunol 153(1):209-10. PMID: 24797280

    McKinnon ML, Rozmus J, Fung SY, Hirschfeld AF, Del Bel KL, Thomas L, Marr N, Martin SD, Marwaha AK, Priatel JJ, Tan R, Senger C, Tsang A, Prendiville J, Junker AK, Seear M, Schultz KR, Sly LM, Holt RA, Patel MS, Friedman JM, Turvey SE (2014). Combined immunodeficiency associated with homozygous MALT1 mutations. J Allergy Clin Immunol 133(5):1458-62,1462.e1-7. PMID: 24332264

    Marr N, Wang TI, Kam SH, Hu YS, Sharma AA, Lam A, Markowski J, Solimano A, Lavoie PM, Turvey SE (2014). Attenuation of Respiratory Syncytial Virus-Induced and RIG-I-Dependent Type I IFN Responses in Human Neonates and Very Young Children. J Immunol 192(3):948-57. PMID: 24391215

    Fung SY, Sofiyev V, Schneiderman J, Hirschfeld AF, Victor RE, Woods K, Piotrowski JS, Deshpande R, Li SC, de Voogd NJ, Myers CL, Boone C, Andersen RJ, Turvey SE (2014). Unbiased Screening of Marine Sponge Extracts for Anti-inflammatory Agents Combined with Chemical Genomics Identifies Girolline as an Inhibitor of Protein Synthesis. ACS Chem Biol 9(1):247-57. PMID: 24117378

    Stiemsma LT, Turvey SE, Finlay BB (2014). An antibiotic-altered microbiota provides fuel for the enteric foe. Cell Res 24(1):5-6. PMID: 24165893

    Sharma AA, Jen R, Brant R, Ladd M, Huang Q, Skoll A, Senger C, Turvey SE, Marr N, Lavoie PM (2014). Hierarchical maturation of innate immune defences in very preterm neonates. Neonatology 106(1):1-9. PMID: 24603545

    Marr N, Hirschfeld AF, Lam A, Wang S, Lavoie PM, Turvey SE (2014). Assessment of Genetic Associations Between Common Single Nucleotide Polymorphisms in RIG-I-like Receptor and IL-4 Signaling Genes and Severe Respiratory Syncytial Virus Infection in Children: a Candidate Gene Case-Control Study. PLOS ONE 9(6):e100269. PMID: 24949794 

    Wong T, Yeung J, Hildebrand KJ, Junker AK, Turvey SE (2014). Human primary immunodeficiencies causing defects in innate immunity. Curr Opin Allergy Clin Immunol. 13(6):607-13. PMID: 24126612

    Rozmus J, Junker A, Thibodeau ML, Grenier D, Turvey SE, Yacoub W, Embree J, Haddad E, Langley JM, Ramsingh RM, Singh VA, Long R, Schultz KR. (2013). Severe Combined Immunodeficiency (SCID) in Canadian children: a national surveillance study. J Clin Immunol 33(8):1310-6. PMID: 24122030

    Marr N, Turvey SE, Grandvaux N (2013). Pathogen recognition receptor crosstalk in respiratory syncytial virus sensing: a host and cell type perspective. Trends Microbiol. 21(11):568-74. PMID: 24119913

    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 12:48. 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 TLR-induced cytokine production in neonates. Genes Immun 14(4):199-211. PMID: 23782977

    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 1;9(1):4. PMID: 23369242

    Mayer ML, Blohmke CJ, Falsafi R, Fjell CD, Madera L, Turvey SE, Hancock REW (2013). Rescue of dysfunctional autophagy by IDR-1018 attenuates hyperinflammatory responses from cystic fibrosis cells. J Immunol 190(3):1227-38. PMID: 23264659

    Grunau RE, Cepeda IL, Chau CMY, Brummelte S, Weinberg J, Lavoie P, Ladd M, Hirschfeld AF, Russell E, Koren G3, Van Uum S, Brant R, Turvey SE (2013). Neonatal Pain-Related Stress and NFKBIA Genotype are Associated with Altered Cortisol Levels in Preterm Boys at School Age. PLOS ONE 8(9):e73926. PMID: 24066085

    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. Part Part Syst Charact 30(12):1039-1043.

    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.

    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
    • Valerie Tolsma – Administrative Assistant
    • Kate Del Bel – Research Manager
    • Mehul Sharma – Research Assistant
    • Mandy Suen – Research Assistant
    • Shan-Yu (Shane) Fung – Research Associate
    • Hind Sbihi – Post-doctoral Fellow
    • Catherine Biggs – MSc Student
    • Chelsea Cutler – Msc Student
    • Henry Lu – PhD Student
    • Linda Warner – Senior Clinical Research Coordinator, CHILD study
    • Maureen Mooney – Clinical Research Nurse, CHILD study
    • Mary Beckingham – Clinical Research Assistant, CHILD study
    • Lauren Muttucomaroe – Clinical Research Assistant, CHILD study
    • Tamara Coffin – Clinical Research Assistant, CHILD study