ABSTRACT The knowledge gaps this application addresses are how precancerous lesions (i.e. metaplasia) arise and subsequently fuel adenocarcinoma of the stomach. Infection with Helicobacter pylori (H. pylori) and autoimmune gastritis both cause chronic inflammation and increase the risk of gastric cancer. This application includes numerous mouse models and human tissue samples to investigate the importance of immune cells (mast cells and Th2 T cells) and cytokines (IL4 and IL13) in inducing gastric metaplasia and promoting the development of gastric metaplasia and tumorigenesis. Identifying inflammatory cells and signals that initiate metaplasia and drive tumor development could improve the ability to identify individuals at an increased risk of disease progression, and new immune based strategies to prevent and treat preneoplastic lesions associated with gastric diseases, including gastric cancer.

Chronic inflammation in the stomach is associated with gastric diseases, including gastric cancer, a leading cause of cancer related deaths. This proposal is focused on understanding the cellular and molecular mechanisms by which inflammatory cells and cytokines induce gastric metaplasia and its progression to cancer. This knowledge is expected to improve our understanding of inflammation induced metaplasia and inform strategies to diagnose and treat gastric diseases and gastric cancer.