Multicellular organisms can exist only thanks to the signaling pathways, the vast networks of biochemical cascades intertwined with every aspect of cellular life. The major signaling pathways like Notch, Wnt, FGF, JAK/STAT, and TGFb act as key regulators of embryonic development, and drivers of genetic disorders and cancer when deregulated.
Unlike the other pathways, Notch signaling occurs only after direct cell-cell contact, and lacks the amplification steps, making it highly sensitive to perturbations. Almost two decades have passed since the discovery of the potential signaling role of the intracellular domains of Notch ligands (LICDs), yet, their function remains elusive.
We aim to functionally test the “Non-canonical” signaling potential of the LICDs in mammals. We take advantage of existing, rare genetic disorders causing mutations in key motifs of the LICDs (NLS, PDB), recapitulating the pathology in vivo using the mouse model, and investigate the “Non-canonical” aspect of Notch ligand signaling and its relation to Notch/WNT signaling cross-talks. The focus of our research holds the potential for the future development of therapeutics for Notch-driven disease.