The PI3K/PKB(AKT)/FOXO signaling pathway
The signaling emanating from the lipid kinase PI3K is involved in a number of important cellular and organismal functions. In insulin signaling PI3K drives important metabolic features and is the major pathway deregulated in insulin-dependent diabetes, when insulin signaling and hence PI3K signaling is impaired. On the other hand, hyperactive PI3K signaling acts to drive many types of cancer.
Diabetes and cancer are two main age-related diseases and interestingly deregulated insulin/ PI3K signaling towards the FOXO/DAF16 class of transcription factors also impacts lifespan or ageing of various model organisms. Thus, reduced insulin signaling through PI3K/PKB(AKT)/FOXO causes diabetes, hyperactive signaling causes cancer and optimal signaling contributes to optimal (extended) lifespan. We are trying to understand this pivotal role of PI3K signaling in connecting age to disease and thus to understand how age contributes to disease in particular cancer.
Metabolic regulation in cancer and differentiation
We study the interaction between protein signaling networks with that of metabolic pathways. To this end we make use of various model systems and at present this is predominantly the organoid culture system. Small intestinal organoids are studied amongst others at the signal cell level by using various sensors that can monitor different aspects of metabolism (see figure B). We also use all kinds of genetic perturbations in order to understand how metabolism and signaling within a single cell type contribute to the life of this cell type in the context of other cell types.
All projects are highly technology driven and therefore we make use in house of all modern-day technology including mass-spectrometry for proteomics and metabolomics, microscopy for live imaging etc.