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Institute of Molecular Cancer Research
University of Zürich
Winterthurerstr. 190
CH-8057 Zürich
Phone +41-44-635 34 74 Email
Group Members

Funding

University Research Priority Program

Prof. Dr. Müller Anne

Main Field(s) of Research, Abstract
My laboratory studies mechanisms of gastric cancer induction by the bacterial pathogen Helicobacter pylori. We are mainly utilizing a mouse model of infection in which gastric cancer precursor lesions, i.e. epithelial hyperplasia, intestinal metaplasia and dysplasia, develop within 3-6 months post infection. We address questions regarding the cell type of origin/normal cellular counterpart of gastric cancer, the precise sequence of precursor lesions, the role of pro-inflammatory cytokines and other immune modulators in gastric cancer induction, the role of bacterial virulence determinants and the reasons for the dramatic gender differences that are observed in gastric cancer risk. The techniques/reagents we are using include a panel of knock-out, transgenic and pharmacological animal models that are available in the relevant genetic background, as well as histological, immunohistochemical and transcriptional analysis of microdissected tumors and normal tissues. Other ongoing projects in the lab address the pathogenesis of another Helicobacter-associated gastric malignancy, mucosa-associated lymphoid tissue (MALT) lymphoma, the role of the putative bacterial oncogene CagA in tumor formation, and the utility of primary gastric cell cultures in studying oncogenic events triggered by Helicobacter pylori.

Main Fields of Research, Keywords
Helicobacter pylori, gastric cancer, MALT lymphoma, transcriptional profiling, host-pathogen interactions, animal models

Special Techniques and Equipment
We study Helicobacter-associated gastric malignancies and host-pathogen interactions in appropriate animal models. Many standard methods of cell- and molecular biology as well as microscopy are being used routinely in the lab. Transcriptional profiling in combination with laser microdissection is also extensively utilized.

Education and Training
The institute hosts regular seminars with outside speakers. We also hold regular journal clubs, data clubs and group meetings. We welcome Diploma Students, and have frequent opportunities for PhD students and postdocs.

Selected Publications

Craig VJ, Arnold I, Gerke C, Huynh MQ, Wundisch T, Neubauer A, Renner C, Falkow S, Mueller A. Gastric MALT lymphoma B cells express polyreactive, somatically mutated immunoglobulins.Blood. 2009 Nov 17.

Toller IM, Hitzler I, Sayi A, Mueller A. Prostaglandin E2 prevents Helicobacter-induced gastric preneoplasia and facilitates persistent infection in a mouse model. Gastroenterology. 2009 Dec 16.

Mueller A, Sayi A, Hitzler I. Protective and pathogenic functions of T-cells are inseparable during the Helicobacter-host interaction. Discov Med. 2009 Aug;8(41):68-73.

Sayi A, Kohler E, Hitzler I, Arnold I, Schwendener R, Rehrauer H, Müller A. J The CD4+ T cell-mediated IFN-gamma response to Helicobacter infection is essential for clearance and determines gastric cancer risk. Immunol. 2009 Jun 1;182(11):7085-101.

Müller, A., O’Rourke, J., Chu, P., Lee, A. and Falkow, S. The role of Helicobacter pylori and H. pylori-specific T-cells in MALT lymphoma pathogenesis. American Journal of Pathology 167, 797-812 (2005).

Müller, A., Falkow, S and Amieva, M.R.. Helicobacter pylori and gastric cancer: what can be learned by studying the response of gastric epithelial cells to the infection? Special gastric cancer edition of Cancer Epidemiology, Prevention and Biomarkers 14, 1859-1964 (2005)