De-Caf Decoding local crosstalk in tumor formation

Communication between different cell types is essential for many biological processes, both in homeostasis and in disease. In tumour initiation, growth and metastasis, cancer cells receive chemical and physical cues from their microenvironment. Those cues determine how disease progresses and influence proliferation and invasiveness of malignant cells. Understanding the crosstalk between cancer cells and their immediate environment is crucial for development of novel cancer therapies. Thanks to the development of single-cell technologies, the field has begun to sample the complexity and the many functions of the tumour microenvironment. While immune cells are at the forefront of these studies, the mesenchymal fibroblast component is also highly pertinent, yet poorly understood. In this proposal, I will focus on proximal communication between mesenchymal fibroblasts and cancer cells. Using intestinal cancer as a model, I will apply a multimodal approach to investigate the consequences of tissue crosstalk in the first steps of epithelial transformation. First, I will study the two-way crosstalk between epithelium and mesenchymal fibroblasts in vitro (objective 1). Secondly, I will interrogate the response of mesenchymal fibroblasts to epithelial transformation in vivo, by defining newly established fibroblasts subpopulations (objective 2) and studying the spatial modification in the tissue organization induced by crypt hyperproliferation using high resolution confocal imaging (objective 3). In sum, I will consider the effect that epithelial transformation have on the surrounding fibroblasts gene expression as well as spatial organization, and I will link subsequent changes to the role that resident fibroblasts play in tumor progression.

Horizon Europe - MSCA Postdoctoral Fellowships 2023 (HORIZON-MSCA-2023-PF-01)

Zentrum für Biologische Wissenschaften