Project Details
Projekt
Deciphering the role of microbial metabolites in modulating MAPK and Wnt signalling and treatment resistance in colorectal cancer
Subject Area
Gastroenterology
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 537604907
Gut microbiota and microbiota-derived metabolites have been linked to treatment response in colorectal cancer (CRC), however, their role in oncogenic signalling and impact on drug efficacy in CRC have not been fully addressed. We raise the hypothesis that microbial metabolites from the gut microbiome exert substantial effects on oncogenic signalling activity to influence tumour progression and therapy response. We aim to identify and characterise the impact of microbial metabolite perturbations in CRC with a focus on Wnt and MAPK signalling, which play crucial roles in CRC progression. To this end, we will combine phenotypic profiling of signalling pathway activity with transcriptome analysis, thereby establishing a map of metabolite-organoid phenotypes in patient-derived organoid (PDO) models. As Fusobacterium nucleatum (F. nucleatum) has been reported to play a major role in CRC pathogenesis, we will analyse the role of F. nucleatum produced metabolites, including succinic acid, as well as further metabolites and bacterial supernatants analysed in the consortium. Furthermore, new longitudinal PDO lines will be established to facilitate insights in the metabolite-oncogenic signalling-therapy response axis in CRC progression and treatment resistance. Using established and newly generated PDO models, we will then address the potential impact of Wnt and MAPK modifying metabolites in co-targeting strategies and their underlying mechanisms.
DFG Programme
Research Units
