The fibroblast growth factor receptor (FGFR) family includes four receptors that bind 18 ligands called fibroblast growth factors, using heparin as a co-factor. These receptors play important roles in all cell types, but are best known for the critical role that they play in the development of the skeletal system. Many pathogenic mutations of FGFR genes are linked to skeletal, cranial, and other developmental abnormalities in humans. Furthermore, FGFR overexpression and mutations have been reported in a variety of cancers.
We are studying how FGFRs are activated by their ligands and by disease mutations. We have shown that the structural changes in response to the binding of different ligands or to pathogenic mutations can be very different and can result in different modes of activation. Current projects investigate how structural changes in response to ligand impact specific FGFR signaling pathways and overall biological responses.