Markus Stein, Ph.D.
Ph.D., Eberhard Karls University and Max-Planck-Institute for Infection Biology, Tübingen, Germany / University of British Columbia, Vancouver
M.Sc., Eberhard Karls University and Max-Planck-Institute for Infection Biology, Tübingen, Germany
B.Sc., Eberhard Karls University, Tübingen, Germany
Microbiology: Bacterial Pathogenesis
Mechanisms of Pathogenicity I and II
Current Topics in Infection and Immunity
Clinical Microbiology I and II
Dr. Stein's major research interest is to understand the complex interactions between the human pathogen Helicobacter pylori and the eukaryotic cells.
Helicobacter pylori is associated with the development of several gastric diseases including peptic ulcer disease (PUD), MALT-lymphoma, and adenocarcinoma. In fact, Helicobacter is currently the only bacterium considered a human carcinogen. Strains with increased pathogenicity contain specialized virulence factors encoded on the chromosome in a region that was designated as the cag-pathogenicity island. Encoded in cag are a type IV secretion system (TFSS), the CagA virulence factor and proteins with unknown function. Dr. Stein's laboratory demonstrated that CagA is an important toxin that is translocated into the host epithelial cell via the TFSS. CagA is then phosphorylated on tyrosine residues by members of the Src-kinase family and causes important toxic effects including: 1) Induction of dramatic morphological changes of the host epithelial cells and 2) disruption of apical-basolateral cell polarity. These effects depend on the association of CagA with proteins that are crucial components of oncogenic pathways (Src-kinases, Shp-2 phosphatase) and with components of the Par-polarity complex (Par1b).
In summary, Dr. Stein's research broadens our knowledge of the molecular mechanisms contributing to severe gastric diseases.
Hug I, Couturier MR, Rooker MM, Taylor DE, Stein M, Feldman MF. 2010. Helicobacter pylori lipopolysaccharide is synthesized via a novel pathway with an evolutionary connection to protein N-glycosylation. PLoS Pathog. 19;6(3):e1000819.
Nestic D, Miller MC, Quinkert ZT, Stein M, Chait BT, Stebbins CE. 2010. Helicobacter pylori CagA inhibits PAR1-MARK family kinases by mimicking host substrates. Nat Struct Mol Biol. 17(1):130-2. Epub 2009 Dec 6.
Cendron L, Couturier M, Angelini A, Barison N, Stein M, Zanotti G. 2009. The Helicobacter pylori CagD (HP0545, Cag24) protein is essential for CagA translocation and maximal induction of interleukin-8 secretion. J Mol Biol. 386(1):204-17. Epub 2008 Dec 14. 386(1):204-17.
Baltrus, D.A., Amieva, M.R., Covacci, A., Lowe, T.M. Merrell, D.S., Ottemann, K.M., Stein, M., Salama, N.R., and K. Guillemin. 2009. The Complete Genome Sequence of Helicobacter pylori strain G27. J. Bact. 91(1):447-8.
Zeatier, Z., Huynh H., Richard Kanyo, and M. Stein. 2008. CagA of Heliocbacter pylori alters the expression and cellular distribution of host proteins involved in cell signaling. FEMS Microbiol. Letters. 288(2), 227-232. Sep 20. [Epub 2008 Sep 20].
Couturier, M., and M. Stein. 2008. Helicobacter pylori produces unique filaments upon host contact in vitro. Can. J. Microbiol. 54(7):537-48.
Zeaiter, Z., Cohen, D., Müsch, A., Bagnoli, F., Covacci, A., and M. Stein. 2008. Analysis of detergent resistant membranes of Helicobacter pylori infected gastric adenocarcinoma cells reveals a role for MARK2/Par1b in CagA-mediated disruption of cellular polarity. Cell. Microbiol. 10(3):781-94. [Epub 2007 Nov 13].
Couturier, M.R., Tasca, E., Montecucco, C., and M. Stein. 2006. Interaction with CagF is required for translocation of CagA into the host via the Helicobacter pylori type IV secretion system. Infect. Immun. 74(1):273-81.
Bourke, B., Ceponis, P., Chiba, N., et.al.; Canadian Helicobacter Study Group. 2005. Canadian Helicobacter Study Group Consensus Conference: Update on the approach to Helicobacter pylori infection in children and adolescents--an evidence-based evaluation. Can J Gastroenterol. 19(7):399-408. Erratum for authorship in: Can J Gastroenterol. 2005 Aug; 19(8):478.
Stein, M., F. Bagnoli, Halenbeck, R., Rappuoli, R., Fantl, W., and A. Covacci. 2002. c-Src / Lyn kinases activate Helicobacter pylori CagA through tyrosine-phosphorylation of the EPIYA motifs. Molecular Microbiology. 43(4):971-980.
Censini, S., M. Stein, and A. Covacci. 2001. Cellular responses induced after contact with Helicobacter pylori. Curr Opin Microbiol. 4(1):41-46.