• Vallance, Bruce A.

    Titles
    Scientist Level 2, CFRI
    Associate Professor, Division of Gastroenterology, Department of Pediatrics, University of British Columbia
    CH.I.L.D. Foundation Chair in Pediatric Gastroenterology
    Degrees / Designations
    B.Sc., PhD
    Primary Area of Research
    Immunity in Health & Disease
    Secondary Area(s) of Research
    Phone
    604-875-2345 ext. 5118
    Fax
    604-875-3244
    Lab Phone
    Mailing Address
    BC Children's Hospital
    Room K4-201, 4480 Oak Street
    Vancouver, BC V6H 3V4
    Affiliate Websites
    Research Areas
  • Enteric bacterial pathogens
  • Innate immunity
  • Intestinal inflammation
  • Host defense
  • Inflammatory bowel disease
Summary

We co-exist in harmony with huge numbers of bacteria, many within our own gastrointestinal (GI) tracts. On occasion, however, particularly virulent bacteria called pathogens (Salmonella, EHEC O157:H7) infect our intestines and cause severe, even fatal, disease. To fight infections, our immune system must recognize these bacteria as harmful and trigger a protective immune response. Some individuals appear highly susceptible to infections, perhaps because their immune systems are unable to recognize or effectively deal with the bacteria. Inappropriate recognition of pathogens may also contribute to chronic diseases of the GI tract such as Crohn's disease and other inflammatory bowel diseases (IBD). We believe that in IBD an individual’s immune system mistakes harmless bacteria for pathogens and attacks them, causing chronic inflammation. Using immunological and microbiological techniques, we’re learning how our immune systems recognize bacteria in the GI tract. We’re also identifying the factors that can provide resistance or susceptibility to intestinal infections, and exploring the mechanisms underlying the dysfunctional pathogen recognition that can trigger chronic IBD.

Current Projects

Role of intestinal epithelial cells in controlling bacterial infections
Many intestinal bacterial pathogens – including enterohemorrhagic E. coli (EHEC O157:H7), the causative agent of the water poisoning in Walkerton, Ontario – infect the epithelial cells that line our intestines. Our recent work has shown that during such infections, epithelial cells are activated to produce a variety of anti-microbial molecules. Moreover, in vitro studies indicate that EHEC and related pathogens may inject bacterial proteins into infected epithelial cells in order to reduce the production of anti-microbial enzymes by epithelial cells. We are currently identifying the bacterial effector proteins as well as the mechanisms involved in this process.

Mechanisms underlying host susceptibility to enteric pathogens
Additional studies have identified several related mouse strains that are highly susceptible to Citrobacter rodentium, a mouse adapted version of EHEC. Susceptible animals show evidence of inflammation similar to that seen in human inflammatory bowel diseases. Using in vivo imaging, we have identified specific sites in the intestine where susceptibility first manifests, as well as the bacterial virulence factors needed to colonize these sites. We are currently identifying the genes underlying the susceptibility defect in these mice, since a similar defect may predispose humans to increased
 
Role of dendritic cells in mucosal infection and inflammation
Dendritic cells are the sentinel immune cells of the body, trafficking to mucosal sites where they acquire antigen to ultimately present to naïve T cells. Recent work in several laboratories suggests that some bacterial pathogens may infect dendritic cells at intestinal mucosal surfaces, using these cells to shuttle across the intestinal epithelial barrier to cause a systemic infection. We are currently examining the role of dendritic cells in enabling the colonization and infection of the GI tract by invasive bacteria (Salmonella) and non-invasive bacteria (EHEC), as well as their role in causing intestinal inflammation in models of IBD. Our work has also revealed that dendritic cells may actually play an active role in host defense, expressing various anti-microbial effectors. We are currently studying the mechanisms of dendritic cell mediated anti-microbial activity both in vitro and in vivo. A better understanding of the role of dendritic cells in GI inflammation may provide useful targets for improved vaccination against bacterial infections as well as provide therapeutic targets for IBD.

Selected Publications
Valdez Y, Grassl GA, Guttman JA, Coburn B, Gros P, Vallance BA, Finlay BB.: Nramp1 drives an accelerated inflammatory response during Salmonella-induced colitis in mice. Cell Microbiol. 2009 Feb;11(2):351-62.

Valdez Y, Diehl GE, Vallance BA, Grassl GA, Guttman JA, Brown NF, Rosenberger CM, Littman DR, Gros P, Finlay BB.: Nramp1 expression by dendritic cells modulates inflammatory responses during Salmonella Typhimurium infection. Cell Microbiol. 2008 Aug;10(8):1646-61.

Gibson DL, Vallance BA.: Intestinal microbiota are transiently altered during Salmonella-induced gastroenteritis. Expert Rev Gastroenterol Hepatol. 2008 Aug;2(4):525-9.

Khan MA, Bouzari S, Ma C, Rosenberger CM, Bergstrom KS, Gibson DL, Steiner TS, Vallance BA.: Flagellin-dependent and -independent inflammatory responses following infection by enteropathogenic Escherichia coli and Citrobacter rodentium. Infect Immun. 2008 Apr;76(4):1410-22.

Gal-Mor O, Gibson DL, Baluta D, Vallance BA, Finlay BB.: A novel secretion pathway of Salmonella enterica acts as an antivirulence modulator during salmonellosis. PLoS Pathog. 2008 Apr 4;4(4):e1000036.

Vallance B.A., Gunawan M.I., Hewlett B., Bercik P., Van Kampen C., Galeazzi F., Sime P.J., Gauldie J., and Collins S.M. TGF- b 1 gene transfer to the mouse colon leads to intestinal fibrosis. Am. J. Physiol. (Gastrointest. Liver Physiol.), 289(7): G116-G128, 2005.

 

Coburn B., Li Y., Owen D., Vallance B.A., and Finlay B.B. Salmonella typhimurium pathogenicity island-2 is necessary for complete virulence in a mouse model of infectious enterocolitis. Infect. & Immun., 73(6): 3219-3227, 2005.

 

Hardwidge P.R., Deng W., Vallance B.A., Rodriquez-Escudero I. , Cid V.J., Molina M., and Finlay B.B. Modulation of host cytoskeleton function by the enteropathogenic Escherichia coli and Citrobacter rodentium effector protein EspG. Infect. & Immun., 73(5): 2586-2594, 2005.

 

Vallance B.A., Khan M.A., Deng W., Gruenheid S., and Finlay B.B. Modeling enteropathogenic and enterohemorrhagic E. coli infections and disease. Drug Disc. Today: Disease Models, 1(1): 73-79, 2004.

 

Vallance B.A., Dijkstra G., Qiu B.S., van der Waiij L.A. , van Goor H., Jansen P.L.M., Mashimo H., and Collins S.M. The relative contributions of nitric oxide synthase (NOS) isoforms to experimental colitis; endothelial derived NOS maintains mucosal integrity. Am. J. Physiol. (Gastrointest. Liver Physiol.)., 287(10): G865-G874, 2004.

 

Vazquez-Torres A., Vallance B.A., Bergman M.A., Finlay B.B., Cookson, B.T., Jones-Carson J., and Fang F.C. Toll-like receptor 4 dependence of innate and adaptive immunity to Salmonella: Importance of the kupffer cell network. J. Immunol., 172: 6202-6208, 2004.

 

Deng W., Puente J.L., Gruenheid S., Li Y., Vallance B.A., Vazquez A.V., Barba J., Ibarra J.A., O’Donnell P., Metalnikov P., Ashman K., Lee S., Goode D., Pawson T., and Finlay B.B. Dissecting virulence: Systematic and functional analysis of a pathogenicity island. Proc. Natl. Acad. Sci. USA., 101(10): 3597-3602, 2004.

 

Vallance B.A., Deng W., Jacobson K., and Finlay B.B. Host susceptibility to the attaching/effacing bacterial pathogen Citrobacter rodentium. Infect. & Immun., 71(6): 3443-3453, 2003 .

 

Deng W., Vallance B.A., Li Y., Puente J.L., and Finlay B.B. Citrobacter rodentium’s translocated intimin receptor (Tir) is a virulence factor necessary for nucleating actin, intestinal colonization and colonic hyperplasia in mice. Mol. Microbiol., 48(1): 95-115, 2003.

 

Vallance B.A., Deng W., De Grado M., Chan C., Jacobson K., and Finlay B.B. Modulation of inducible nitric oxide synthase (iNOS) expression by the attaching/effacing bacterial pathogen Citrobacter rodentium in mice. Infect. & Immun., 70(11): 6424-6435, 2002 .

Grants
CIHR Operating Grant – Project: "Defining SIGIRR's role in epithelial homeostasis and host defense during infectious colitis" (2013-2018)

NSERC Discovery Grant and Discovery Accelerator Supplement - Project: "Vitamin D - A Regulator of Host-Microbe Interactions in the Mammalian GI Tract?" (2013-2018)

Crohn’s and Colitis Foundation of Canada Discovery Research Grants - Project: "IBD: The result of an imbalance between inflammatory versus tissue protective innate signaling?" (2013-2016)



Honours & Awards

Canadian Children Inflammatory Bowel Disease Network, CIHR and CH.I.L.D Foundation – 2013


CH.I.L.D. Foundation Chair in Pediatric Gastroenterology – 2013-ongoing

Canada Research Chair in Pediatric Gastroenterology (Tier II) – 2004-2009


Michael Smith Foundation for Health Research Scholar – 2004-2009


CH.I.L.D. Foundation Research Scholar – 2003-2013

Research Group Members

Dr. Mohammed Rumi – Postdoctoral fellow

Dr. Mohammed Khan – Graduate student

Mr. Kirk Bergstrom – Graduate student

Ms. Yanet Valdez – Graduate student

Ms. Caixia Ma – Research technician

Ms. Tina Huang – Research assistant