In this sub-project, we aim to study epigenetic reprogramming of tumor associated macrophages based on metabolic factors derived from the tumor microenvironment. We will employ innovative 3D organoid co-culture models generated from human and mouse colorectal tissues and explore the metabolic crosstalk of macrophages with normal and cancer tissues in these models. In collaboration with other project partners, we will associate specific metabolic states of the organoids, reflecting the normal or malignant colon environment, with epigenetic alterations in macrophages based on the metabolic analysis of organoid/macrophage co-cultures (T. Weichhart, E. Pohl, A. Haschemi). Further, we will study epigenetic regulation in macrophages using LOF experiments in transgenic mouse models and organoid cultures in vitro. This will allow us to identify epigenetic pathways that might affect immunometabolism and macrophage phenotypes in the tumor setting and serve as potential therapeutic targets (M. Schweiger, C. Moissl-Eichinger, G. Schabbauer, T. Weichhart).

Janette Pfneissl
PhD student
SFB Member

Kristina Draganic
PhD student
SFB Member