Project Details
Projekt
Microbial influences on colorectal cancer liver metastasis metabolism and therapy response
Applicants
Professorin Dr. Laura Hinze; Dr. Jens Puschhof
Subject Area
Gastroenterology
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 537604907
The colorectal cancer (CRC)-associated microbiome is at the centre of intense research that has recently uncovered important microbial roles in mutagenesis, signalling, metabolism and treatment response. While compelling evidence exists for microbial colonisation of CRC liver metastases, little is known about the functional implications of this intra-metastasis microbiome. Nevertheless, it is highly plausible that tumour cells and bacterial strains which co-migrate from the gut to the liver microenvironment share co-dependencies which impact their behaviour at the metastatic site. For this reason, we hypothesise that microbiome-derived factors shape the metabolic state, metastasis phenotypes and thereby therapy response in CRC metastases. In the proposed project, we thus aim to analyse the interdependencies of microbial metabolites and the host cell metabolic state at the distant site using in vivo as well as targeted in vitro CRISPR approaches, and to utilise patient-derived organoids in the presence of bacterial strains to analyse how patient-derived bacterial strains shape cell competition, metastasis cell behaviour and treatment response. Collectively, the obtained results are expected to yield insights into the interplay of microbiome and metabolic changes to drive niche independence and treatment response. Thereby, they will be important factors to address the overarching consortium aims of characterising the interactions of cancer genomic alterations with microbiota and their metabolites, and to increase druggability and accessibility of key targets and pathways in CRC.
DFG Programme
Research Units
