Signalling networks for stemness and tumorigenesis

We are exploring how signalling networks activated by extra-cellular signals are tightly regulated to establish the fate of cells. We focus our studies on signals triggered by receptor tyrosine kinases (RTKs), their requirement during mouse development, how deregulation of these signalling mediators leads to pathologies like neuro-degeneration and cancer, and how their modulation can be effective for targeted molecular therapies. By using the HGF/Met system, we have investigated how unique biological events are triggered by RTK during mouse development. This question has been addressed by interfering with RTK signalling properties during mouse embryogenesis. Our previous work has shown that specific effectors downstream RTK are required to achieve distinct biological read outs, such as cell survival, migration, differentiation, proliferation and axonal outgrowth. These studies also showed that the outcome of signalling by RTK is refined by the cell type, based on their distinct developmental histories. We have also investigated how the requirement of pathways for a given biological response triggered by RTK is established. This work has revealed that cells superimpose the outcome of signals required for a given response.

Our current research is focused on three specific goals:
- we are searching for novel mediators of RTK-triggered cell survival and dissecting the signalling components required for their activation. We combine pharmacological and genetic approaches to alter signalling modulators in cultured cells and in animal models. Biochemical studies are applied to elucidate components of signalling networks (survival routes).
- we are searching for novel compounds with inhibitory properties towards specific targets like the RTK Met (see collaborator). We rely on a multidisciplinary approach that integrates chemistry and computer modelling into biology for drug discovery (hit Met).
- we are investigating how extracellular signals control self-renewal, maintenance, differentiation and survival of neural progenitors and neurons. We integrate in vitro studies on ES cells with mouse genetics (instructive signals).