Researchers Search Results

MBBS, DPhil, FRCPC

604-875-2345 ext. 5094

604-875-2226

604-875-3131

Child & Family Research Institute
A5-145, 950 West 28th Avenue
Vancouver, BC V5Z 4H4

• 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

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.

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.

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.

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.

Aaron Hirschfeld – Lab Manager
Nico Marr – Research Associate
Shan-Yu (Shane) Fung – Research Associate
Anthony Tang – Graduate Student
Karolynn Hsu – Graduate Student
Sandy Hu – COOP student
Tina Wang - COOP student
Maia Kaplan – Undergraduate Student
Shirley Wang - Undergraduate Student
Sophie Wang - Undergraduate Student
Mary Ann Mauro - Senior Clinical Research Coordinator, CHILD study
Maureen Campbell – Financial Manager, CHILD study
Rossitta Yung - Clinical Research Assistant, CHILD study
Maria Penner - Clinical Research Assistant, CHILD study
Olivia Kitt - Clinical Research Assistant, CHILD study
Debbie Windover - Research Nurse, CHILD study
Linda Warner - Research Nurse, CHILD study
Laura Fitzgerald - Research Nurse, CHILD study
Susan Menzies - Clinical Research Assistant, CHILD study
Jennifer Kwan - Clinical Research Assistant, CHILD study
Ghazal Assadian - Clinical Research Assistant, CHILD study
Emma Kim - Clinical Research Assistant, CHILD study
Claire Lepine - Clinical Research Assistant, CHILD study
Sabrina Takhar - Clinical Research Assistant, CHILD study
Emily Rousseau - Clinical Research Assistant, CHILD study
Gina Faigen - Clinical Research Assistant, CHILD study
Anna Louise Young - Clinical Research Assistant, CHILD study
Brittany Seligman - Clinical Research Assistant, CHILD study

Robbie Mamonluk - Clinical Research Assistant, CHILD study