Gerhard, Markus

Gastrointestinal infections. Gastrointestinal tumorigenesis

In recent years, we have focused on the interaction of Helicobacter pylori with the immune system, specifically on virulence factors involved in immune-evasion. Based on promising new antigens identified in recent years, we are also working on developing H. pylori vaccines based on a combination of new antigens, adjuvants and formulations. We are further exploing how H. pylori contributes to carcinogenesis in the stomach, which virulence factors are employed, and which host signaling pathways are activated during cancer initiation and progression.

The canonical Wnt signaling pathway is essential in developmental processes and plays a crucial role in the regulation of epithelial stem cell self-renewal. Deregulation of this pathway is associated with carcinogenesis, particularly in the gastrointestinal tract. We identified a target gene of the Wnt signaling pathway, RNF43, which is selectively expressed in intestinal stem cells and is overexpressed in colorectal adenomas and a subset of colorectal cancers. Mutations of RNF43 have been identified in several tumor types, suggesting an important role for RNF43 as a tumor suppressor gene. Indeed, depletion of RNF43 expression in colon and gastric cells increases their tumorigenic potential (Neumeyer et al. Carcinogenesis 2019). To further explore the function of RNF43 we have generated two mouse models expressing mutated Rnf43. Mutations in Rnf43 lead to gastric hyperproliferation, which is exacerbated upon H. pylori infection (Neumeyer et al. Cancers 2019). We are also analyzing the mutation status of RNF43 in human gastroinstestinal tumor samples to determine the role of RNF43 in colon and gastric cancer.