Unravelling the role of Notch signalling in disease
Notch signalling is a highly conserved transduction pathway that plays a pivotal role in cell differentiation and fate during development. Notch receptors on one cell interact with transmembrane signals in another cell, and through a cascade of events, certain target genes become activated. Accumulating evidence shows that Notch signalling deregulation is implicated in various diseases ranging from leukaemia to breast cancer and vascular disease. The EU-funded NOTCHIT (Notch signaling in development and pathology) project set out to develop state-of-the-art molecular tools to study Notch signalling. The long-term aim was to utilise the pathway to direct stem cell differentiation and to correct aberrant Notch signalling in different pathologies. The consortium recruited young and experienced researchers and established a European network that offered a training program and inter-laboratory visits. Researchers worked in various scientific projects ranging from basic science to the use of pharmacological interventions to control Notch signalling. NOTCHIT researchers identified novel Notch-related molecular and cellular mechanisms involved in haematopoiesis, brain development, heart and muscle. Their experiments provided novel insight into the role of deregulated Notch signalling in stroke, breast cancer and leukaemia. Furthermore, the results obtained from different experimental models were used to design novel therapeutic approaches. Collectively, the project generated fundamental knowledge into the Notch pathway and increased the understanding of pathophysiology of several diseases. Major emphasis was given to the translational nature of the obtained information towards new therapeutic approaches.
Notch signalling, cell differentiation, development, leukaemia, stroke