Paul Scherrer Institut,
Kurt Ballmer-Hofer focused his research at PSI on the structural and functional analysis of receptor tyrosine kinases, in particular on Vascular Endothelial Growth Factor Receptors, VEGFRs. In collaboration with partner labs his team solved the structures of VEGF ligands, the ligand binding domain of VEGFR-2, and -3, and of the full-length extracellular domain of VEGFR-1 in complex with VEGF. The data of these studies led to the discovery of allosteric receptor regulatory sites in subdomains 4, 5 and 7. Antibodies and DARPins specifically binding to these domains showed strong inhibition of receptor activation and downstream signaling both in vitro and in vivo in angiogenesis model systems.
Structural analysis of vascular endothelial growth factor receptors reveals drug-targetable allosteric sites regulating angiogenesis