Helicobacter pylori infection is causally associated with gastritis and peptic ulcer, as well as two gastric malignancies, gastric carcinoma and B-cell-mucosa-associated lymphoid tissue (MALT) lymphoma. Our proposed research focuses on the application of genetic and molecular tools to manipulate the H. pylori chromosome and the use of DNA microarray technology to monitor both the host and the pathogen in H. pylori animal models of infection and disease. Specifically, we propose to examine the H. pylori infection of mice and Mongolian gerbil. While none of the cell culture models or the animal models we propose to use can fully reflect what is seen in humans, the mouse model of infection can be used to productively investigate how H. pylori colonizes the stomach. We wish to follow long-term infection of the mouse and the host cell response to long-term H. pylori carriage measured by transcriptional profile changes as compared to uninfected littermates. Also, the mouse infection model is useful to study one form of malignancy caused by H. pylori, MALT lymphoma, and we propose to study this feature of long-term H. pylori murine infection by both bacterial transcription profiling and by the use of a mouse DNA microarray to follow the host response and changes that occur in the malignant transformation. We also propose to identify bacterial genes essential for gastric colonization and persistence in the stomach using a method developed in our laboratory called MicroArray Transposon Tagging (MATT) strategy. H. pylori infection reflects a particularly intriguing example of a host-pathogen interaction. The microbe serves as a tool to understand host cell biology and malignancy. The response of the bacterium to the host cell environment allows us to understand the essence of bacterial pathogenicity.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA092229-04
Application #
6772629
Study Section
Metabolic Pathology Study Section (MEP)
Program Officer
Daschner, Phillip J
Project Start
2001-07-01
Project End
2005-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
4
Fiscal Year
2004
Total Cost
$294,089
Indirect Cost
Name
Stanford University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
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