Associate Professor and Associate Head, Division of Infectious Diseases
Associate Member, Department of Microbiology and Immunology, UBC
phone: 6048754111
fax: 6048754762

Education

Duke University, MD
Harvard, Biochemical Sciences, BSc

The Role of Flagellin in Anti-Bacterial Inflammatory Responses

We study the inflammatory response to the flagellin from enteroaggregative E. coli (EAEC), an emerging diarrheal pathogen. Bacterial flagellins are recognized by Toll-like receptor 5 (TLR5), leading to NF-kB activation, chemokine release, T-cell activation, and other inflammatory phenotypes. Our work is currently focused on several key projects:

  1. Studies of molecular inflammatory signalling in response to bacterial flagellin acting through Toll-like receptor 5 (TLR5).
  2. Identifying the role of flagellin/TLR5 interaction in the abnormal inflammatory responses that characterize Crohn’s disease
  3. Studies of flagellin-reactive effector and regulatory populations of T cells in the human gut in inflammatory bowel disease
  4. Pathogenic mechanisms of infectious diarrhea due to enteroaggregative E. coli

 

Clinical Expertise

General consultative infectious diseases, with a particular interest in infectious diarrhea and tropical medicine

Selected Publications

The worst of both worlds: examining the hypervirulence of the shigatoxigenic/enteroaggregative Escherichia coli O104:H4. Steiner TS. J Infect Dis. 2014 Dec 15;210(12):1860-2. doi: 10.1093/infdis/jiu400. Epub 2014 Jul 18. PMID:25038259

Meta-analysis in microbiology. Pabalan N, Jarjanazi H, Steiner TS. Indian J Med Microbiol. 2014 Jul-Sep;32(3):229-35. doi: 10.4103/0255-0857.136547. Review. PMID:25008812

A non-synonymous coding variant (L616F) in the TLR5 gene is potentially associated with Crohn’s disease and influences responses to bacterial flagellin. Sheridan J, Mack DR, Amre DK, Israel DM, Cherkasov A, Li H, Grimard G, Steiner TS. PLoS One. 2013 Apr 11;8(4):e61326. doi: 10.1371/journal.pone.0061326. Print 2013. PMID:23593463

Helios+ and Helios- cells coexist within the natural FOXP3+ T regulatory cell subset in humans. Himmel ME, MacDonald KG, Garcia RV, Steiner TS, Levings MK. J Immunol. 2013 Mar 1;190(5):2001-8. doi: 10.4049/jimmunol.1201379. Epub 2013 Jan 28. PMID:23359504

Enteroaggregative Escherichia coli and acute diarrhea in children: a meta-analysis of South Asian populations. Pabalan N, Singian E, Jarjanazi H, Steiner TS. Eur J Clin Microbiol Infect Dis. 2013 May;32(5):597-607. doi: 10.1007/s10096-012-1779-3. Epub 2012 Nov 21. PMID:23179250

ATP conditions intestinal epithelial cells to an inflammatory state that promotes components of DC maturation. Yao Y, Levings MK, Steiner TS. Eur J Immunol. 2012 Dec;42(12):3310-21. doi: 10.1002/eji.201142213. Epub 2012 Oct 26. PMID:22987503

Regulatory T-cell therapy for inflammatory bowel disease: more questions than answers. Himmel ME, Yao Y, Orban PC, Steiner TS, Levings MK. Immunology. 2012 Jun;136(2):115-22. doi: 10.1111/j.1365-2567.2012.03572.x. Review. PMID:22348589

Toll-like receptor 5 deficiency protects from wasting disease in a T cell transfer colitis model in T cell receptor-β-deficient mice. Hardenberg G, Yao Y, Piccirillo CA, Levings MK, Steiner TS. Inflamm Bowel Dis. 2012 Jan;18(1):85-93. doi: 10.1002/ibd.21738. Epub 2011 Oct 29. PMID:22038840

Environmental influences on T regulatory cells in inflammatory bowel disease. Hardenberg G, Steiner TS, Levings MK. Semin Immunol. 2011 Apr;23(2):130-8. doi: 10.1016/j.smim.2011.01.012. Epub 2011 Feb 3. Review. PMID: 21295492

Human CD4+ FOXP3+ regulatory T cells produce CXCL8 and recruit neutrophils. Himmel ME, Crome SQ, Ivison S, Piccirillo C, Steiner TS, Levings MK. Eur J Immunol. 2011 Feb;41(2):306-12. doi: 10.1002/eji.201040459. Epub 2011 Jan 11. PMID:21268001

The p110α and p110β isoforms of class I phosphatidylinositol 3-kinase are involved in toll-like receptor 5 signaling in epithelial cells. Ivison SM, Khan MA, Graham NR, Shobab LA, Yao Y, Kifayet A, Sly LM, Steiner TS. Mediators Inflamm. 2010;2010. pii: 652098. doi: 10.1155/2010/652098. Epub 2010 Oct 3. PMID:20953381

The stress signal extracellular ATP modulates antiflagellin immune responses in intestinal epithelial cells. Ivison SM, Himmel ME, Mayer M, Yao Y, Kifayet A, Levings MK, Steiner TS. Inflamm Bowel Dis. 2011 Jan;17(1):319-33. doi: 10.1002/ibd.21428. Epub 2010 Aug 18. PMID: 20722064

Oxidative stress enhances IL-8 and inhibits CCL20 production from intestinal epithelial cells in response to bacterial flagellin. Ivison SM, Wang C, Himmel ME, Sheridan J, Delano J, Mayer ML, Yao Y, Kifayet A, Steiner TS. Am J Physiol Gastrointest Liver Physiol. 2010 Sep;299(3):G733-41. doi: 10.1152/ajpgi.00089.2010. Epub 2010 Jul 1. PMID:20595617

Protein kinase D1 and D2 are involved in chemokine release induced by toll-like receptors 2, 4, and 5. Steiner TS, Ivison SM, Yao Y, Kifayet A. Cell Immunol. 2010;264(2):135-42. doi: 10.1016/j.cellimm.2010.05.012. Epub 2010 May 27. PMID:20557879

Autoactivation of the AggR regulator of enteroaggregative Escherichia coli in vitro and in vivo. Morin N, Tirling C, Ivison SM, Kaur AP, Nataro JP, Steiner TS. FEMS Immunol Med Microbiol. 2010 Apr;58(3):344-55. doi: 10.1111/j.1574-695X.2010.00645.x. Epub 2010 Jan 28. PMID:20132305

The single IgG IL-1-related receptor controls TLR responses in differentiated human intestinal epithelial cells. Khan MA, Steiner TS, Sham HP, Bergstrom KS, Huang JT, Assi K, Salh B, Tai IT, Li X, Vallance BA. J Immunol. 2010 Mar 1;184(5):2305-13. doi: 10.4049/jimmunol.0900021. Epub 2010 Feb 3. PMID:20130217

TLR5 is not required for flagellin-mediated exacerbation of DSS colitis. Ivison SM, Himmel ME, Hardenberg G, Wark PA, Kifayet A, Levings MK, Steiner TS. Inflamm Bowel Dis. 2010 Mar;16(3):401-9. doi: 10.1002/ibd.21097.PMID:19774646

Anti-flagellin antibodies in irritable bowel syndrome: another attack on our commensals? Ivison SM, Steiner TS. Neurogastroenterol Motil. 2008 Oct;20(10):1081-5. doi: 10.1111/j.1365-2982.2008.01199.x. Review. No abstract available. PMID:18826558

The role of T-regulatory cells and Toll-like receptors in the pathogenesis of human inflammatory bowel disease. Himmel ME, Hardenberg G, Piccirillo CA, Steiner TS, Levings MK.Immunology. 2008 Oct;125(2):145-53. doi: 10.1111/j.1365-2567.2008.02939.x. Review.PMID:18798918

Flagellin-dependent and -independent inflammatory responses following infection by enteropathogenic Escherichia coli and Citrobacter rodentium. Khan MA, Bouzari S, Ma C, Rosenberger CM, Bergstrom KS, Gibson DL, Steiner TS, Vallance BA.Infect Immun. 2008 Apr;76(4):1410-22. doi: 10.1128/IAI.01141-07. Epub 2008 Jan 28.PMID:18227166

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