• Speert, David

    Titles
    Senior Clinician Scientist and Head, Centre for Understanding and Preventing Infection in Children, CFRI
    Sauder Family Professor, Division of Infectious and Immunological Diseases, Department of Pediatrics, University of British Columbia
    Degrees / Designations
    MD, FRCP(C)
    Primary Area of Research
    Immunity in Health & Disease
    Secondary Area(s) of Research
    Phone
    604-875-2472
    Fax
    604-875-2226
    Lab Phone
    604-875-2469
    Assistant
    Carolyn Smith
    Assistant Phone
    604-875-2438
    Mailing Address
    Room A5-175, 950 West 28th Avenue
    Vancouver, BC V5Z 4H4
    Affiliate Websites
    Research Areas
  • Infection of the lung in patients with cystic fibrosis
  • Pathogenesis of Burkholderia cepacia complex
  • Innate host defense mechanisms, particularly of the lung
  • Molecular epidemiology of bacterial infection
  • Mechanisms of disease susceptibility in HIV-exposed but uninfected babies in South Africa
Summary

Research in Dr. Speert’s laboratory is directed at gaining a clearer understanding of function of the human innate immune system and the control of inflammation in health and disease. Investigations are currently underway to identify both bacterial and host determinants of dysfunctional inflammation.

Work in Dr. Speert’s laboratory has focused for the past 30 years on the causes of bacterial infections in cystic fibrosis. His work has identified a number of bacterial and host factors which likely conspire to create an environment in the CF lung which favors infection with the bacteria, Pseudomonas aeruginosa and Burkholderia cepacia complex. These studies are ultimately directed at identifying novel strategies to prevent or enhance therapy of such infections.

Since 2006, Dr. Speert has worked to establish a durable collaboration with colleagues in South Africa where childhood disease is far more common and more severe than in North America. His group is now studying children born to, but not infected by, mothers who are HIV-positive. These children experience severe infections during the first year of life for reasons that are unexplained. He has established a birth cohort study in Cape Town and is planning a cohort study of older children in Paarl, Western Cape Province to better understand the causes for morbidity and mortality in these infants and to determine if they are protected against HIV when exposed later in life.

Research in Dr. Speert’s laboratory is supported with grants from the Canadian Institutes of Health Research, the Cystic Fibrosis Canada, the BC Lung Association, BC Children’s Hospital Foundation, the Martha Piper Fund (UBC) and the Peter Wall Institute for Advanced Studies.

Current Projects

Innate defence of the lung against bacterial infection
This research, funded by the Canadian Institutes of Health Research and the Canadian Bacterial Diseases Network, is directed at gaining a clearer understanding of the host pattern recognition mechanisms for host defence of the lung against inhaled pathogens. Work is focussed on macrophages, polymorphonuclear leukocytes and dendritic cells and the role of specific receptor-ligand interactions.

Pathogenesis of bacterial infection in patients with cystic fibrosis
This research, funded by Cystic Fibrosis Canada and the British Columbia Lung Association, is directed at gaining a clearer understanding of the pathogenesis of lung infections with Pseudomonas aeruginosa and Burkholderia cepacia complex. Specific areas of research include analysis of biofilm formation/quorum sensing, evaluation of mechanisms of evasion of normal host defence mechanisms and molecular epidemiology for analysis of possible patient-to-patient spread.

Mechanisms for enhanced morbidity and mortality in HIV-exposed but uninfected (HEU) babies.
Babies born to HIV-infected mothers are usually not infected themselves, escape from infection being enhanced by anti-retroviral therapy in mother and infant around the time of delivery. A pilot cohort study in collaboration with colleagues at Stellenbosch University in South Africa has confirmed the enhanced morbidity of HEU babies, and immunological studies are beginning to unravel some of the causes. A larger cohort study is planned to commence in 2011 and will explore in greater depth the preliminary observations made during the pilot study. This collaborative interaction has provided opportunities for trainees from both South Africa and Canada to gain experience in advanced innate immunology and in international health.

Selected Publications

Zlosnik JEA, Speert DP. The Role of Mucoidy in Virulence of Bacteria from the Burkholderia cepacia Complex: A Systematic Proteomic and Transcriptomic Analysis. J Inf Dis;202(5):770-81, 2010. PMID: 20670172

Zlosnik JEA, Costa PS, Brant R, Mori PYB, Hird TJ, Fraenkel MC, Wilcox PG, Davidson AG, Speert DP. Mucoid and nonmucoid Burkholderia cepacia complex bacteria in cystic fibrosis infections. Am J Respir Crit Care Med, 2010. PMID: 20709823

Eftekhar F, Speert DP. Biofilm formation by persistent and non-persistent isolates of Staphylococcus epidermidis from a neonatal intensive care unit. Journal of Hospital Infection; 71(2):112-116, 2009. PMID: 19013672

Bauernfeind FG, Horvath G, Stutz A, Alnemri ES, MacDonald KL, Speert DP, Fernandes-Alnemri T, Wu J, Monks BG, Fitzgerald KA, Hornung V, Latz E. NF-kB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J Immunol;183:787-791, 2009. PMID: 19570822

MacDonald KL, Speert DP.: Differential modulation of innate immune cell functions by the Burkholderia cepacia complex: Burkholderia cenocepacia but not Burkholderia multivorans disrupts maturation and induces necrosis in human dendritic cells. Cell Microbiol. 2008 Oct;10(10):2138-49. PMID: 18624797

Brown KL, Bylund J, MacDonald KL, Song-Zhao GX, Elliott MR, Falsafi R, Hancock RE, Speert DP.: ROS-deficient monocytes have aberrant gene expression that correlates with inflammatory disorders of chronic granulomatous disease. Clin Immunol. 2008 Oct;129(1):90-102. PMID: 18676204

Zlosnik JEA, Hird TJ, Fraenkel MC, Moreira LM, Henry DA, Speert DP. Differential mucoid exopolysaccharide production by members of the Burkholderia cepacia complex. J. Clin. Microbiol; 46(4):1470-3, April 2008. PMID: 18256220

MacDonald KL, Speert DP. Differential modulation of innate immune cell functions by the Burkholderia cepacia complex: Burkholderia cenocepacia but not Burkholderia multivorans disrupts maturation and induces necrosis in human dendritic cells. Cellular Microbiology; 10(10):2138-2149, 2008. PMID: 18624797

Brown KL, Bylund J, MacDonald KL, Song-Zhao GX, Elliott MR, Falsafi R, Hancock REW, Speert DP. ROS-deficient Monocytes have Aberrant Gene Expression that Correlate with Inflammatory Disorders of Chronic Granulomatous Disease. Clinical Immunology; 129(1):90-102, 2008. PMID: 18676204

Bylund J, MacDonald KL, Brown KL, Mydel P, Collins LV, Hancock REW, Speert DP. Enhanced inflammatory responses of chronic granulomatous disease leukocytes involve ROS-independent activation of NF-kB. European Journal of Immunology. 2007 April;37(4):1087-96. PMID: 17330823

Chung JW, Speert DP. Proteomic identification and characterization of bacterial factors associated with Burkholderia cenocepacia survival in a murine host. Microbiology Jan 2007;153(Pt 1): 206-214. PMID: 17185549

Davidson DJ, Currie AJ, Bowdish DME, Brown KL, Rosenberger CM, Ma RC, Bylund J, Campsall P, Puel A, Picard C, Casanova JL, Turvey SE, Hancock REW, Devon RS, Speert DP. IRAK-4 Mutation (Q293X): Rapid Detection and Characterization of Defective Post-transcriptional TLR/IL-1R Responses in Human Myeloid and Non-myeloid cells. J.Immunol. 2006 Dec1;177(11):8202-11. PMID: 17114497

Khashu M, Osiovich H, Henry D, Al Khotani A, Solimano A, Speert DP. Persistent bacteremia and severe thrombocytopenia caused by coagulase negative Staphylococcus in a neonatal intensive care unit. Pediatrics 117(2):340-348, 2006 Feb. PMID: 16452352

Bylund J, Burgess LA, Cescutti P, Ernst R, Speert DP. Exopolysaccharides from Burkholderia cenocepacia inhibit neutrophil chemotaxis and scavenge reactive oxygen species. J. Biol. Chem. 2006 Feb 3;281(5):2526-32. PMID: 16316987

Bylund J, Campsall PA, Ma RC, Conway BA, Speert DP. Burkholderia cenocepacia induces neutrophil necrosis in chronic granulomatous disease. J. Immunol. 174(6):3562-3569, 2005Mar15. PMID: 15749893

Davidson DJ, Currie AJ, Reid GSD, Bowdish DME, MacDonald KL, Ma RC, Hancock REW, Speert DP. The cationic antimicrobial peptide LL-37 modulates dendritic cell differentiation and dendritic cell-induced T cell polarization. J. Immunology. 172(2):1146-1156, 2004. PMID: 14707090

Currie AJ, Davidson DJ, Reid GSD, Bharya S, MacDonald KL, Devon RS, Speert DP. Primary immunodeficiency to pneumococcal infection due to a defect in toll-like receptor signaling. J. Pediatr. 144(4):512-518, 2004 April. PMID: 15069402

Pollard AJ, Currie A, Rosenberger CM, Heale JP, Finlay BB, Speert DP. Differential post-transcriptional activation of human phagocytes by different Pseudomonas aeruginosa isolates. Cellular Microbiology. 6(7):639-650, 2004. PMID: 15186400

Conway BA, Chu KK, Bylund J, Altman E, Speert DP. Production of exopolysaccharide by Burkholderia cenocepacia results in altered cell-surface interactions and altered bacterial clearance in mice. J. Infect. Dis. 190(5):957-966, 2004. PMID: 15295701

Grants

Cystic Fibrosis Canada (2011) ~ Project: Investigations into the determinants of Burkholderia cepacia complex bacterial virulence.

Peter Wall Institute for Advanced Studies, The University of BC(2011) ~ Project: HIV-Exposed but Uninfected (HEU) Infants: Exploration of the Causes of Enhanced Morbidity and Mortality.

Canadian Institutes of Health Research Operating Grant (2010) ~ Project: The role of innate phagocytic function in control of inflammation from infection or injury.

BC Lung Association (2009) ~ Project: Defining the Response of the Innate Immune System to Mucoid and Non-mucoid Burkholderia cepacia complex.

Honours & Awards
Ivory Tower Award, presented by the Paediatric Residents for teaching, UBC - 2008
Sauder Family Chair, UBC - 2007
Team leader, Research Team of Distinction, Dept. of Pediatrics, UBC - 2004
Ivory Tower Award, presented by the Paediatric Residents for teaching, UBC - 2002
Research Group Members

Maureen Campbell - Lab Manager
Deborah Henry - Technician
Trevor Hird - Technician
Tracy Lee - Technician
Agatha Jassem - PhD student
Rossi Billie Velapatino - PhD student
James Zlosnik, PhD - Postdoctoral Fellow
Rebecca Malott, PhD - Postdoctoral Fellow
Alexander Persson, PhD - Postdoctoral Fellow
Allison McDonald - PhD student
Amy Slogrove, MD – Graduate student