Third party funded individual grant
Acronym: CH-DFG_SBH_BR 5196/4-1
Start date : 16.08.2026
End date : 15.08.2029
The microenvironment at metastatic target sites determines the success of disseminating tumour cells to establish a metastatic colony. In metastasis of pancreatic ductal adenocarcinoma (PDAC) cancer associated fibroblasts (CAFs) are forming a very heterogeneous tumour microenvironment. This is reflected by activation of the EMT-inducing transcription factor ZEB1 in only a subset of CAFs. We hypothesize that ZEB1 is a crucial determinant of CAF subtype specification and function that drives disease progression. We will identify and analyse different CAF subpopulations and the role of ZEB1 in the process of colonization. We apply transplantation and genetic mouse tumour models, scRNA sequencing, ex vivo organ slice microscopy and human PDAC organoid-CAF co-cultures to address these hypothesis. With our findings on specific CAF subtypes, we hope to identify new therapeutic approaches targeting protumourigenic functions of the microenvironment during colonization.