Research & Publications
Cellular signaling initiated by fibroblast growth factors (FGFs) controls many essential physiological processes during normal embryonic development and homeostasis in adult animals. Accordingly, a variety of human diseases are caused by genetic disruption or aberrant regulation of FGF-dependent cell signaling pathways. Members of the FGF family stimulate their cellular responses by binding to the extracellular domains of the four members of the fibroblast growth factor receptors (FGFRs), a family of receptor tyrosine kinases (RTKs).
Canonical FGFs activate FGFRs via paracrine or autocrine mechanisms, in a process that requires the action of an FGF ligand together with heparan sulfate proteoglycans (HSPG) that function as critical co-receptors for FGFs. Endocrine FGFs (FGF19, FGF21, and FGF23), on the other hand, activate FGFRs through signaling mechanism distinct from the mechanism underlying the action of canonical FGFs. Their signaling through FGFR requires binding to the Klotho family of surface receptors; FGF23 signaling requires α-Klotho, while FGF19 and FGF21 signaling requires β-Klotho. Endocrine FGFs function as hormones to regulate important metabolic functions such as bile acid synthesis, lipogenesis, energy expenditure, and phosphate excretion.
The primary goal of our laboratory is to understand the mechanism of cellular signaling by endocrine FGFs at molecular level. We use biochemical, biophysical and structural techniques to investigate detailed interactions between molecules involved in endocrine FGF signaling. The outcome of our studies could provide insights for the development of therapeutic agents for diseases such as diabetes, cancer, and rickets.