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 Canadian Cystic Fibrosis Foundation, the BC Lung Association, BC Children’s Hospital Foundation, the Martha Piper Fund (UBC) and the Peter Wall Institute for Advanced Studies.

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 the Canadian Cystic Fibrosis Foundation 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.

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

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.
 
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.

Bylund J, Macdonald KL, Brown KL, Mydel P, Collins LV, Hancock RE, Speert DP.: Enhanced inflammatory responses of chronic granulomatous disease leukocytes involve ROS-independent activation of NFkappa B. Eur J Immunol. 2007 Apr;37(4):1087-96.

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

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.

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

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.

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.

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

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

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

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

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

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

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

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

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

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

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

Maureen Campbell - Lab Manager
Deborah Henry - Technician
Trevor Hird - Technician
Tracy Lee - Technician
Agatha Jassem - PhD student
Rossi Billie Velapatino - PhD student
Kelly MacDonald, PhD - Postdoctoral Fellow
James Zlosnik, PhD - Postdoctoral Fellow
Rebecca Malott, PhD - Postdoctoral Fellow
Alexander Persson, PhD - Postdoctoral Fellow
Allison McDonald - Master's student
Brad Locke - Medical student
Lourdes (Cynthia) Gunaratnam - Directed Studies student