Leading the way in H. pylori research
One H. pylori determinant associated with increased gastric cancer risk is the cag pathogenicity island, and several cag genes encode components of a type IV secretion system (T4SS) which exports a bacterial oncoprotein, CagA, into host cells.
Our group has demonstrated that this virulence locus also translocates components of peptidoglycan and microbial DNA into host cells, triggering aberrant signaling cascades that heighten oncogenic risk. For example, we have shown that H. pylori cag+ strains selectively activate β-catenin and a stem cell population marked by Lrig1, as well as the EGF receptor, host effectors that influence carcinogenesis.
We have also demonstrated that environmental factors associated with gastric cancer such as iron deficiency, augment the ability of H. pylori to induce gastric cancer via enhanced production of bile acids and augmented assembly of the cag T4SS. Aberrant stem cell activation is linked to carcinogenesis and our research has shown that chronic H. pylori infection stimulates Lrig1-expressing progenitor cells in a cag-dependent manner, which promotes gastric carcinogenesis.
Finally, we have recently demonstrated that specific members of the non-H. pylori microbial community collaborate with H. pylori to drive the development of gastric cancer.
