Research Projects

CagA-positive Helicobacter pylori infection is the primary cause of gastric cancer, the third leading cause of cancer mortality. CagA down-regulates key DNA repair genes, leading to genome instability and causing replication fork collapse, double strand breaks, and reduced Homologues Recombination. Despite its role in cancer development, CagA has been found non-essential for tumor maintenance. Recent research has led to the 'Hit and Run' model of H-pylori mediated carcinogenesis. A recent finding suggests the accumulation of a distinctive mutation pattern in highly transcribed regions and chromosome ends. However, establishing a connection between CagA infection and the mutation profile is challenging due to the multistep process and longer duration of tumor development. This proposal aims to understand the impact of CagA on host chromosome structure and genome organization using a well-established gastric cancer model. A doxycycline-inducible system will be used to address the impact of CagA expression on chromosomal structural aberrations, with a focus on DNA topological changes and alternative B-DNA structures. Hi-C experiments will be conducted to understand the effect of CagA on genome three-dimensional organization and identify specific chromatin domains and regions susceptible for H.pylori infection. This research will answer key questions about molecular events leading to down-regulation of DNA repair processes and the mechanisms causing carcinogenesis associated with H.pylori.