Overview

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.

Publications

DNBS/TNBS colitis models: providing insights into inflammatory bowel disease and effects of dietary fat.
Morampudi, V. and Bhinder, G. and Wu, X. and Dai, C. and Sham, H.P. and Vallance, B.A. and Jacobson, K.
2014

TACI deficiency enhances antibody avidity and clearance of an intestinal pathogen
Tsuji, S. and Stein, L. and Kamada, N. and Nuñez, G. and Bram, R. and Vallance, B.A. and Sousa, A.E. and Platt, J.L. and Cascalho, M.
DOI: 10.1172/JCI74428
2014

Indispensable functions of ABL and PDGF receptor kinases in epithelial adherence of attaching/effacing pathogens under physiological conditions
Manthey, C.F. and Calabio, C.B. and Wosinski, A. and Hanson, E.M. and Vallance, B.A. and Groisman, A. and Martín, M.G. and Wang, J.Y.J. and Eckmann, L.
DOI: 10.1152/ajpcell.00013.2014
2014

Intestinal epithelium-specific MyD88 signaling impacts host susceptibility to infectious colitis by promoting protective goblet cell and antimicrobial responses
Bhinder, G. and Stahl, M. and Sham, H.P. and Crowley, S.M. and Morampudi, V. and Dalwadi, U. and Ma, C. and Jacobson, K. and Vallance, B.A.
DOI: 10.1128/IAI.02045-14
2014

A Novel Mouse Model of Campylobacter jejuni Gastroenteritis Reveals Key Pro-inflammatory and Tissue Protective Roles for Toll-like Receptor Signaling during Infection
Stahl, M. and Ries, J. and Vermeulen, J. and Yang, H. and Sham, H.P. and Crowley, S.M. and Badayeva, Y. and Turvey, S.E. and Gaynor, E.C. and Li, X. and Vallance, B.A.
DOI: 10.1371/journal.ppat.1004264
2014

The Citrobacter rodentium mouse model: studying pathogen and host contributions to infectious colitis.
Bhinder, G. and Sham, H.P. and Chan, J.M. and Morampudi, V. and Jacobson, K. and Vallance, B.A.
2013

Activation of p38a in T cells regulates the intestinal host defense against attaching and effacing bacterial infections
Shim, E.-J. and Bang, B.-R. and Kang, S.-G. and Ma, J. and Otsuka, M. and Kang, J. and Stahl, M. and Han, J. and Xiao, C. and Vallance, B.A. and Kang, Y.J.
DOI: 10.4049/jimmunol.1300908
2013

Requirement of epithelial integrin-linked kinase for facilitation of Citrobacter rodentium-induced colitis
Assi, K. and Bergstrom, K. and Vallance, B. and Owen, D. and Salh, B.
DOI: 10.1186/1471-230X-13-137
2013

The mucin muc2 limits pathogen burdens and epithelial barrier dysfunction during salmonella enterica serovar typhimurium colitis
Zarepour, M. and Bhullar, K. and Montero, M. and Ma, C. and Huang, T. and Velcich, A. and Xia, L. and Vallance, B.A.
DOI: 10.1128/IAI.00854-13
2013

CD4+ T cells drive goblet cell depletion during citrobacter rodentium infection
Chan, J.M. and Bhinder, G. and Sham, H.P. and Ryz, N. and Huang, T. and Bergstrom, K.S. and Vallance, B.A.
DOI: 10.1128/IAI.00655-13
2013

SIGIRR, a Negative Regulator of TLR/IL-1R Signalling Promotes Microbiota Dependent Resistance to Colonization by Enteric Bacterial Pathogens
Sham, H.P. and Yu, E.Y.S. and Gulen, M.F. and Bhinder, G. and Stahl, M. and Chan, J.M. and Brewster, L. and Morampudi, V. and Gibson, D.L. and Hughes, M.R. and McNagny, K.M. and Li, X. and Vallance, B.A.
DOI: 10.1371/journal.ppat.1003539
2013

Bacterial stimulation of the TLR-MyD88 pathway modulates the homeostatic expression of ileal paneth cell a-defensins
Menendez, A. and Willing, B.P. and Montero, M. and Wlodarska, M. and So, C.C. and Bhinder, G. and Vallance, B.A. and Finlay, B.B.
DOI: 10.1159/000341630
2013

Resistin-like molecule a promotes pathogenic Th17 cell responses and bacterial-induced intestinal inflammation
Osborne, L.C. and Joyce, K.L. and Alenghat, T. and Sonnenberg, G.F. and Giacomin, P.R. and Du, Y. and Bergstrom, K.S. and Vallance, B.A. and Nair, M.G.
DOI: 10.4049/jimmunol.1200706
2013

Active vitamin D (1,25-dihydroxyvitamin D3) increases host susceptibility to Citrobacter rodentium by suppressing mucosal Th17 responses
Ryz, N.R. and Patterson, S.J. and Zhang, Y. and Ma, C. and Huang, T. and Bhinder, G. and Wu, X. and Chan, J. and Glesby, A. and Sham, H.P. and Dutz, J.P. and Levings, M.K. and Jacobson, K. and Vallance, B.A.
DOI: 10.1152/ajpgi.00320.2012
2012

MyD88 signaling promotes both mucosal homeostatic and fibrotic responses during Salmonella-induced colitis
Månsson, L.E. and Montero, M. and Zarepour, M. and Bergstrom, K.S. and Ma, C. and Huang, T. and Man, C. and Grassl, G.A. and Vallance, B.A.
DOI: 10.1152/ajpgi.00038.2012
2012

Regulated virulence controls the ability of a pathogen to compete with the gut microbiota
Kamada, N. and Kim, Y.-G. and Sham, H.P. and Vallance, B.A. and Puente, J.L. and Martens, E.C. and Núñez, G.
DOI: 10.1126/science.1222195
2012

Innate host responses to enteric bacterial pathogens: A balancing act between resistance and tolerance
Bergstrom, K.S. and Sham, H.P. and Zarepour, M. and Vallance, B.A.
DOI: 10.1111/j.1462-5822.2012.01750.x
2012

Attaching and effacing bacterial effector NleC suppresses epithelial inflammatory responses by inhibiting NF-¿B and p38 mitogen-activated protein kinase activation
Sham, H.P. and Shames, S.R. and Croxen, M.A. and Ma, C. and Chan, J.M. and Khan, M.A. and Wickham, M.E. and Deng, W. and Finlay, B.B. and Vallance, B.A.
DOI: 10.1128/IAI.05033-11
2011

Antibiotic treatment alters the colonic mucus layer and predisposes the host to exacerbated Citrobacter rodentium-induced colitis
Wlodarska, M. and Willing, B. and Keeney, K.M. and Menendez, A. and Bergstrom, K.S. and Gill, N. and Russell, S.L. and Vallance, B.A. and Finlay, B.B.
DOI: 10.1128/IAI.01104-10
2011

Colonic microbiota alters host susceptibility to infectious colitis by modulating inflammation, redox status, and ion transporter gene expression
Ghosh, S. and Dai, C. and Brown, K. and Rajendiran, E. and Makarenko, S. and Baker, J. and Ma, C. and Halder, S. and Montero, M. and Ionescu, V.A. and Klegeris, A. and Vallance, B.A. and Gibson, D.L.
DOI: 10.1152/ajpgi.00509.2010
2011

Citrobacter rodentium infection induces MyD88-dependent formation of ubiquitinated protein aggregates in the intestinal epithelium
Kaniuk, N.A. and Lam, G.Y. and Ma, C. and Galindo-Mata, E. and Jones, N. and Vallance, B.A. and Brumell, J.H.
DOI: 10.1159/000320644
2011

The pathogenic E. coli type III effector EspZ interacts with host CD98 and facilitates host cell prosurvival signalling
Shames, S.R. and Deng, W. and Guttman, J.A. and de Hoog, C.L. and Li, Y. and Hardwidge, P.R. and Sham, H.P. and Vallance, B.A. and Foster, L.J. and Finlay, B.B.
DOI: 10.1111/j.1462-5822.2010.01470.x
2010

Interleukin-11 reduces TLR4-induced colitis in TLR2-deficient mice and restores intestinal STAT3 signaling
Gibson, D.L. and Montero, M. and Ropeleski, M.J. and Bergstrom, K.S.B. and Ma, C. and Ghosh, S. and Merkens, H. and Huang, J. and Mnsson, L.E. and Sham, H.P. and McNagny, K.M. and Vallance, B.A.
DOI: 10.1053/j.gastro.2010.06.057
2010

Dissemination of invasive Salmonella via bacterial-induced extrusion of mucosal epithelia
Knodler, L.A. and Vallance, B.A. and Celli, J. and Winfree, S. and Hansen, B. and Montero, M. and Steele-Mortimer, O.
DOI: 10.1073/pnas.1006098107
2010

Loss of single immunoglobulin interlukin-1 receptor-related molecule leads to enhanced colonic polyposis in Apcmin mice
Xiao, H. and Yin, W. and Khan, M.A. and Gulen, M.F. and Zhou, H. and Sham, H.P. and Jacobson, K. and Vallance, B.A. and Li, X.
DOI: 10.1053/j.gastro.2010.04.043
2010

The single IgG IL-1-related receptor controls TLR responses in differentiated human intestinal epithelial cells
Khan, M.A. and Steiner, T.S. and Sham, H.P. and Bergstrom, K.S. and Huang, J.T. and Assi, K. and Salh, B. and Tai, I.T. and Li, X. and Vallance, B.A.
DOI: 10.4049/jimmunol.0900021
2010

Control of Intestinal Homeostasis, Colitis, and Colitis-Associated Colorectal Cancer by the Inflammatory Caspases
Dupaul-Chicoine, J. and Yeretssian, G. and Doiron, K. and Bergstrom, K.S.B. and McIntire, C.R. and LeBlanc, P.M. and Meunier, C. and Turbide, C. and Gros, P. and Beauchemin, N. and Vallance, B.A. and Saleh, M.
DOI: 10.1016/j.immuni.2010.02.012
2010

Gut barrier disruption by an enteric bacterial pathogen accelerates insulitis in NOD mice
Lee, A.S. and Gibson, D.L. and Zhang, Y. and Sham, H.P. and Vallance, B.A. and Dutz, J.P.
DOI: 10.1007/s00125-009-1626-y
2010

Muc2 protects against lethal infectious colitis by disassociating pathogenic and commensal bacteria from the colonic mucosa
Bergstrom, K.S.B. and Kissoon-Singh, V. and Gibson, D.L. and Ma, C. and Montero, M. and Sham, H.P. and Ryz, N. and Huang, T. and Velcich, A. and Finlay, B.B. and Chadee, K. and Vallance, B.A.
DOI: 10.1371/journal.ppat.1000902
2010

Epithelial p38a controls immune cell recruitment in the colonic mucosa
Kang, Y.J. and Otsuka, M. and van den Berg, A. and Hong, L. and Huang, Z. and Wu, X. and Zhang, D.-W. and Vallance, B.A. and Tobias, P.S. and Han, J.
DOI: 10.1371/journal.ppat.1000934
2010

Absence of stearoyl-CoA desaturase-1 does not promote DSS-induced acute colitis
MacDonald, M.L.E. and Bissada, N. and Vallance, B.A. and Hayden, M.R.
DOI: 10.1016/j.bbalip.2009.08.001
2009

Vasoactive intestinal peptide ameliorates intestinal barrier disruption associated with Citrobacter rodentium-induced colitis
Conlin, V.S. and Wu, X. and Nguyen, C. and Dai, C. and Vallance, B.A. and Buchan, A.M.J. and Boyer, L. and Jacobson, K.
DOI: 10.1152/ajpgi.90551.2008
2009

Salmonella infection of gallbladder epithelial cells drives local inflammation and injury in a model of acute typhoid fever
Menendez, A. and Arena, E.T. and Guttman, J.A. and Thorson, L. and Vallance, B.A. and Vogl, W. and Finlay, B.
DOI: 10.1086/646608
2009

Innate immunity and microbes: Conversations with the gut leading to intestinal tissue repair and fibrosis
Gibson, D.L. and Montero, M. and Ryz, N.R. and Vallance, B.A.
DOI: 10.2174/187152309789152002
2009

Nramp1 drives an accelerated inflammatory response during Salmonella -induced colitis in mice
Valdez, Y. and Grassl, G.A. and Guttman, J.A. and Coburn, B. and Gros, P. and Vallance, B.A. and Finlay, B.B.
DOI: 10.1111/j.1462-5822.2008.01258.x
2009

Flagellin-dependent and -independent inflammatory responses following infection by enteropathogenic Escherichia coli and Citrobacter rodentium
Khan, M.A. and Bouzari, S. and Ma, C. and Rosenberger, C.M. and Bergstrom, K.S.B. and Gibson, D.L. and Steiner, T.S. and Vallance, B.A.
DOI: 10.1128/IAI.01141-07
2008

A novel secretion pathway of Salmonella enterica acts as an antivirulence modulator during salmonellosis
Gal-Mor, O. and Gibson, D.L. and Baluta, D. and Vallance, B.A. and Finlay, B.B.
DOI: 10.1371/journal.ppat.1000036
2008

Intestinal microbiota are transiently altered during Salmonella-induced gastroenteritis
Gibson, D.L. and Vallance, B.A.
DOI: 10.1586/17474124.2.4.525
2008

Nramp1 expression by dendritic cells modulates inflammatory responses during Salmonella Typhimurium infection
Valdez, Y. and Diehl, G.E. and Vallance, B.A. and Grassl, G.A. and Guttman, J.A. and Brown, N.F. and Rosenberger, C.M. and Littman, D.R. and Gros, P. and Finlay, B.B.
DOI: 10.1111/j.1462-5822.2008.01155.x
2008

Chronic Enteric Salmonella Infection in Mice Leads to Severe and Persistent Intestinal Fibrosis
Grassl, G.A. and Valdez, Y. and Bergstrom, K.S.B. and Vallance, B.A. and Finlay, B.B.
DOI: 10.1053/j.gastro.2007.12.043
2008

Toll-like receptor 2 plays a critical role in maintaining mucosal integrity during Citrobacter rodentium-induced colitis
Gibson, D.L. and Ma, C. and Rosenberger, C.M. and Bergstrom, K.S.B. and Valdez, Y. and Huang, J.T. and Khan, M.A. and Vallance, B.A.
DOI: 10.1111/j.1462-5822.2007.01052.x
2008

Modulation of intestinal goblet cell function during infection by an attaching and effacing bacterial pathogen
Bergstrom, K.S.B. and Guttman, J.A. and Rumi, M. and Ma, C. and Bouzari, S. and Khan, M.A. and Gibson, D.L. and Vogl, A.W. and Vallance, B.A.
DOI: 10.1128/IAI.00093-07
2008

MyD88 signalling plays a critical role in host defence by controlling pathogen burden and promoting epithelial cell homeostasis during Citrobacterrodentium-induced colitis
Gibson, D.L. and Ma, C. and Bergstrom, K.S.B. and Huang, J.T. and Man, C. and Vallance, B.A.
DOI: 10.1111/j.1462-5822.2007.01071.x
2008

Role of M-CSF-dependent macrophages in colitis is driven by the nature of the inflammatory stimulus
Ghia, J.-E. and Galeazzi, F. and Ford, D.C. and Hogaboam, C.M. and Vallance, B.A. and Collins, S.
DOI: 10.1152/ajpgi.00453.2007
2008

Aggregation via the red, dry, and rough morphotype is not a virulence adaptation in Salmonella enterica serovar typhimurium
White, A.P. and Gibson, D.L. and Grassl, G.A. and Kay, W.W. and Finlay, B.B. and Vallance, B.A. and Surette, M.G.
DOI: 10.1128/IAI.01383-07
2008

Saccharomyces boulardii ameliorates Citrobacter rodentium-induced colitis through actions on bacterial virulence factors
Wu, X. and Vallance, B.A. and Boyer, L. and Bergstrom, K.S.B. and Walker, J. and Madsen, K. and O'Kusky, J.R. and Buchan, A.M. and Jacobson, K.
DOI: 10.1152/ajpgi.00173.2007
2007

The Toll-Interleukin-1 Receptor Member SIGIRR Regulates Colonic Epithelial Homeostasis, Inflammation, and Tumorigenesis
Xiao, H. and Gulen, M.F. and Qin, J. and Yao, J. and Bulek, K. and Kish, D. and Altuntas, C.Z. and Wald, D. and Ma, C. and Zhou, H. and Tuohy, V.K. and Fairchild, R.L. and de la Motte, C. and Cua, D. and Vallance, B.A. and Li, X.
DOI: 10.1016/j.immuni.2007.02.012
2007

The adaptor Act1 is required for interleukin 17 - Dependent signaling associated with autoimmune and inflammatory disease
Qian, Y. and Liu, C. and Hartupee, J. and Altuntas, C.Z. and Gulen, M.F. and Jane-Wit, D. and Xiao, J. and Lu, Y. and Giltiay, N. and Liu, J. and Kordula, T. and Zhang, Q.-W. and Vallance, B. and Swaidani, S. and Aronica, M. and Tuohy, V.K. and Hamilton, T. and Li, X.
DOI: 10.1038/ni1439
2007

Genetic profiling of dendritic cells exposed to live- or ultraviolet-irradiated Chlamydia muridarum reveals marked differences in CXC chemokine profiles
Zaharik, M.L. and Nayar, T. and White, R. and Ma, C. and Vallance, B.A. and Straka, N. and Jiang, X. and Rey-Ladino, J. and Shen, C. and Brunham, R.C.
DOI: 10.1111/j.1365-2567.2006.02488.x
2007

IL-4 gene transfer to the small bowel serosa leads to intestinal inflammation and smooth muscle hyperresponsiveness
Vallance, B.A. and Radojevic, N. and Hogaboam, C.M. and Deng, Y. and Gauldie, J. and Collins, S.M.
DOI: 10.1152/ajpgi.00065.2006
2007

Citrobacter rodentium infection causes both mitochondrial dysfunction and intestinal epithelial barrier disruption in vivo: Role of mitochondrial associated protein (Map)
Ma, C. and Wickham, M.E. and Guttman, J.A. and Deng, W. and Walker, J. and Madsen, K.L. and Jacobson, K. and Vogl, W.A. and Finlay, B.B. and Vallance, B.A.
DOI: 10.1111/j.1462-5822.2006.00741.x
2006

Toll-like receptor 4 contributes to colitis development but not to host defense during Citrobacter rodentium infection in mice
Khan, M.A. and Ma, C. and Knodler, L.A. and Valdez, Y. and Rosenberger, C.M. and Deng, W. and Finlay, B.B. and Vallance, B.A.
DOI: 10.1128/IAI.74.5.2522-2536.2006
2006

Noradrenergic and cholinergic neural pathways mediate stress-induced reactivation of colitis in the rat
Saunders, P.R. and Miceli, P. and Vallance, B.A. and Wang, L. and Pinto, S. and Tougas, G. and Kamath, M. and Jacobson, K.
DOI: 10.1016/j.autneu.2005.12.002
2006

Salmonella enterica serovar Typhimurium pathogenicity island 2 is necessary for complete virulence in a mouse model of infectious enterocolitis
Coburn, B. and Li, Y. and Owen, D. and Vallance, B.A. and Finlay, B.B.
DOI: 10.1128/IAI.73.6.3219-3227.2005
2005

Modulation of host cytoskeleton function by the enteropathogenic Escherichia coli and Citrobacter rodentium effector protein EspG
Hardwidge, P.R. and Deng, W. and Vallance, B.A. and Rodriguez-Escudero, I. and Cid, V.J. and Molina, M. and Finlay, B.B.
DOI: 10.1128/IAI.73.5.2586-2594.2005
2005

TGF-ß1 gene transfer to the mouse colon leads to intestinal fibrosis
Vallance, B.A. and Gunawan, M.I. and Hewlett, B. and Bercik, P. and Van Kampen, C. and Galeazzi, F. and Sime, P.J. and Gauldie, J. and Collins, S.M.
DOI: 10.1152/ajpgi.00051.2005
2005

Cloning vectors and fluorescent proteins can significantly inhibit Salmonella enterica virulence in both epithelial cells and macrophages: Implications for bacterial pathogenesis studies
Knodler, L.A. and Bestor, A. and Ma, C. and Hansen-Wester, I. and Hensel, M. and Vallance, B.A. and Steele-Mortimer, O.
DOI: 10.1128/IAI.73.10.7027-7031.2005
2005

Salmonella pathogenicity island 2 is expressed prior to penetrating the intestine
Brown, N.F. and Vallance, B.A. and Coombes, B.K. and Valdez, Y. and Coburn, B.A. and Finlay, B.B.
DOI: 10.1371/journal.ppat.0010032
2005

Myenteric plexus injury and apoptosis in experimental colitis
Boyer, L. and Ghoreishi, M. and Templeman, V. and Vallance, B.A. and Buchan, A.M. and Jevon, G. and Jacobson, K.
DOI: 10.1016/j.autneu.2004.10.006
2005

Modeling enteropathogenic and enterohemorrhagic E. coli infections and disease
Vallance, B.A. and Khan, M.A. and Deng, W. and Gruenheid, S. and Finlay, B.B.
DOI: 10.1016/j.ddmod.2004.04.001
2004

Relative contributions of NOS isoforms during experimental colitis: Endothelial-derived NOS maintains mucosal integrity
Vallance, B.A. and Dijkstra, G. and Qiu, B. and Van Der Waaij, L.A. and Van Goor, H. and Jansen, P.L.M. and Mashimo, H. and Collins, S.M.
DOI: 10.1152/ajpgi.00187.2004
2004

SseK1 and SseK2 are novel translocated proteins of Salmonella enterica serovar Typhimurium
Kujat Choy, S.L. and Boyle, E.C. and Gal-Mor, O. and Goode, D.L. and Valdez, Y. and Vallance, B.A. and Finlay, B.B.
DOI: 10.1128/IAI.72.9.5115-5125.2004
2004

Dissecting virulence: Systematic and functional analyses of a pathogenicity island
Deng, W. and Puente, J.L. and Gruenheid, S. and Li, Y. and Vallance, B.A. and Vázquez, A. and Barba, J. and Ibarra, J.A. and O'Donnell, P. and Metalnikov, P. and Ashman, K. and Lee, S. and Goode, D. and Pawson, T. and Finlay, B.B.
DOI: 10.1073/pnas.0400326101
2004

Toll-Like Receptor 4 Dependence of Innate and Adaptive Immunity to Salmonella: Importance of the Kupffer Cell Network
Vazquez-Torres, A. and Vallance, B.A. and Bergman, M.A. and Finlay, B.B. and Cookson, B.T. and Jones-Carson, J. and Fang, F.C.
2004

Clearance of Citrobacter rodentium requires B cells but not secretory immunoglobulin A (IgA) or IgM antibodies
Maaser, C. and Housley, M.P. and Iimura, M. and Smith, J.R. and Vallance, B.A. and Finlay, B.B. and Schreiber, J.R. and Varki, N.M. and Kagnoff, M.F. and Eckmann, L.
DOI: 10.1128/IAI.72.6.3315-3324.2004
2004

Salmonella type III effectors PipB and PipB2 are targeted to detergent-resistant microdomains on internal host cell membranes
Knodler, L.A. and Vallance, B.A. and Hensel, M. and Jäckel, D. and Finlay, B.B. and Steele-Mortimer, O.
DOI: 10.1046/j.1365-2958.2003.03598.x
2003

Host susceptibility to the attaching and effacing bacterial pathogen Citrobacter rodentium
Vallance, B.A. and Deng, W. and Jacobson, K. and Finlay, B.B.
DOI: 10.1128/IAI.71.6.3443-3453.2003
2003

Citrobacter rodentium translocated intimin receptor (Tir) is an essential virulence factor needed for actin condensation, intestinal colonization and colonic hyperplasia in mice
Deng, W. and Vallance, B.A. and Li, Y. and Puente, J.L. and Finlay, B.B.
DOI: 10.1046/j.1365-2958.2003.03429.x
2003

Erratum: SopD2 is a novel type III secreted effector of Salmonella typhimurium that targets late endocytic compartments upon delivery into host cells (Traffic (2003) vol. 4 (1) (36-48))
Brumell, J.H. and Kujat-Choy, S. and Brown, N.F. and Vallance, B.A. and Knodler, L.A. and Finlay, B.B.
2003

SseA is required for translocation of Salmonella pathogenicity island-2 effectors into host cells
Coombes, B.K. and Brown, N.F. and Kujat-Choy, S. and Vallance, B.A. and Finlay, B.B.
DOI: 10.1016/S1286-4579(03)00094-7
2003

SopD2 is a novel type III secreted effector of Salmonella typhimurium that targets late endocytic compartments upon delivery into host cells
Brumell, J.H. and Kujat-Choy, S. and Brown, N.F. and Vallance, B.A. and Knodler, L.A. and Finlay, B.B.
DOI: 10.1034/j.1600-0854.2003.40106.x
2003

Salmonella effectors within a single pathogenicity island are differentially expressed and translocated by separate type III secretion systems
Knodler, L.A. and Celli, J. and Hardt, W.-D. and Vallance, B.A. and Yip, C. and Finlay, B.B.
DOI: 10.1046/j.1365-2958.2002.02820.x
2002

Modulation of inducible nitric oxide synthase expression by the attaching and effacing bacterial pathogen Citrobacter rodentium in infected mice
Vallance, B.A. and Deng, W. and De Grado, M. and Chan, C. and Jacobson, K. and Finlay, B.B.
DOI: 10.1128/IAI.70.11.6424-6435.2002
2002

Enteropathogenic and enterohemorrhagic Escherichia coli infections: Emerging themes in pathogenesis and prevention
Vallance, B.A. and Chan, C. and Robertson, M.L. and Finlay, B.B.
2002

Host-pathogen interactions: Host resistance factor Nramp1 up-regulates the expression of Salmonella pathogenicity island-2 virulence genes
Zaharik, M.L. and Vallance, B.A. and Puente, J.L. and Gros, P. and Finlay, B.B.
DOI: 10.1073/pnas.252415599
2002

Current progress in enteropathogenic and enterohemorrhagic Escherichia coli vaccines
Horne, C. and Vallance, B.A. and Deng, W. and Finlay, B.B.
DOI: 10.1586/14760584.1.4.483
2002

Mice lacking T and B lymphocytes develop transient colitis and crypt hyperplasia yet suffer impaired bacterial clearance during Citrobacter rodentium infection
Vallance, B.A. and Deng, W. and Knodler, L.A. and Finlay, B.B.
DOI: 10.1128/IAI.70.4.2070-2081.2002
2002

Neural change in Trichinella-infected mice is MHC II independent and involves M-CSF-derived macrophages
Galeazzi, F. and Lovato, P. and Blennerhassett, P.A. and Haapala, E.M. and Vallance, B.A. and Collins, S.M.
2001

IL-12 gene transfer alters gut physiology and host immunity in nematode-infected mice
Khan, W.I. and Blennerhassett, P.A. and Deng, Y. and Gauldie, J. and Vallance, B.A. and Collins, S.M.
2001

Enteropathogenic Escherichia coli infection induces expression of the early growth response factor by activating mitogen-activated protein kinase cascades in epithelial cells
De Grado, M. and Rosenberger, C.M. and Gauthier, A. and Vallance, B.A. and Finlay, B.B.
DOI: 10.1128/IAI.69.10.6217-6224.2001
2001

Locus of enterocyte effacement from Citrobacter rodentium: Sequence analysis and evidence for horizontal transfer among attaching and effacing pathogens
Deng, W. and Li, Y. and Vallance, B.A. and Finlay, B.B.
DOI: 10.1128/IAI.69.10.6323-6335.2001
2001

Role of immunologic factors and cyclooxygenase 2 in persistent postinfective enteric muscle dysfunction in mice
Barbara, G. and De Giorgio, R. and Deng, Y. and Vallance, B. and Blennerhassett, P. and Collins, S.M.
2001

Critical role for signal transducer and activator of transcription factor 6 in mediating intestinal muscle hypercontractility and worm expulsion in Trichinella spiralis-infected mice
Khan, W.I. and Vallance, B.A. and Blennerhassett, P.A. and Deng, Y. and Verdu, E.F. and Matthaei, K.I. and Collins, S.M.
DOI: 10.1128/IAI.69.2.838-844.2001
2001

Mast cell-independent impairment of host defense and muscle contraction in T. spiralis-infected W/Wv mice
Vallance, B.A. and Blennerhassett, P.A. and Huizinga, J.D. and Collins, S.M.
2001

Exploitation of host cells by enteropathogenic Escherichia coli
Vallance, B.A. and Finlay, B.B.
DOI: 10.1073/pnas.97.16.8799
2000

Interleukin-5 deficient mice exhibit impaired host defence against challenge Trichinella spiralis infections
Vallance, B.A. and Matthaei, K.I. and Sanovic, S. and Young, I.G. and Collins, S.M.
DOI: 10.1046/j.1365-3024.2000.00328.x
2000

Inflammation-induced impairment of enteric nerve function in nematode- infected mice is macrophage dependent
Galeazzi, F. and Haapala, E.M. and Van Rooijen, N. and Vallance, B.A. and Collins, S.M.
2000

CD4 T cells and major histocompatibility complex class II expression influence worm expulsion and increased intestinal muscle contraction during Trichinella spiralis infection
Vallance, B.A. and Galeazzi, F. and Collins, S.M. and Snider, D.P.
1999

Putative inflammatory and immunological mechanisms in functional bowel disorders
Collins, S.M. and Vallance, B. and Barbara, G. and Borgaonkar, M.
DOI: 10.1053/bega.1999.0037
1999

Characterization of enteric functional changes evoked by in vivo anti- CD3 T cell activation
Radojevic, N. and McKay, D.M. and Merger, M. and Vallance, B.A. and Collins, S.M. and Croitoru, K.
1999

Stress, inflammation and the irritable bowel syndrome.
Collins, S.M. and Barbara, G. and Vallance, B.
1999

IL-5 contributes to worm expulsion and muscle hypercontractility in a primary T. spiralis infection
Vallance, B.A. and Blennerhassett, P.A. and Deng, Y. and Matthaei, K.I. and Young, I.G. and Collins, S.M.
1999

The role of CD4+ lymphocytes in the susceptibility of mice to stress- induced reactivation of experimental colitis
Qiu, B.S. and Vallance, B.A. and Blennerhassett, P.A. and Collins, S.M.
DOI: 10.1038/13503
1999

T lymphocyte-dependent and -independent intestinal smooth muscle dysfunction in the T. spiralis-infected mouse
Vallance, B.A. and Croitoru, K. and Collins, S.M.
1998

T cell-mediated exocrine pancreatic damage in major histocompatibility complex class II-deficient mice
Vallance, B.A. and Hewlett, B.R. and Snider, D.P. and Collins, S.M.
DOI: 10.1016/S0016-5085(98)70270-7
1998

The effect of nematode infection upon intestinal smooth muscle function
Vallance, B.A. and Collins, S.M.
DOI: 10.1046/j.1365-3024.1998.00155.x
1998

Increased intestinal muscle contractility and worm expulsion in nematode-infected mice
Vallance, B.A. and Blennerhassett, P.A. and Collins, S.M.
1997

Persistent intestinal neuromuscular dysfunction after acute nematode infection in mice
Barbara, G. and Vallance, B.A. and Collins, S.M.
DOI: 10.1053/gast.1997.v113.pm9322517
1997

Therapeutic effects of interleukin-4 gene transfer in experimental inflammatory bowel disease
Hogaboam, C.M. and Vallance, B.A. and Kumar, A. and Addison, C.L. and Graham, F.L. and Gauldie, J. and Collins, S.M.
1997

Role of smooth muscle in intestinal inflammation
Collins, S.M. and Khan, I. and Vallance, B. and Hogaboam, C. and Barbara, G.
1996

Research

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.

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 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.

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

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

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

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

Research Group Members

Hyungjun Yang
Shauna Crowley, Doctoral Student
Caixia Ma, Research Assistant / Research Technician
Franziska Graef
Hongbing Yu, Research Associate
Else Bosman, Doctoral Student
Larissa Celiberto, Doctoral Student
Martin Stahl, Postdoctoral Fellow
Joannie Allaire
Jingtian Huang, Research Assistant
Navjit Moore, Summer Student
James Sader, Undergraduate Student
Tina Madani Kia
Qiaochu Liang, Graduate Student
Hong Ting Law, Postdoctoral Fellow
Genelle Healey, Postdoctoral Fellow
Hyun-Jeong Ko, Visiting Associate Professor
Vivian Han, Graduate Student