C u r r e n t I n t e r e s t
Membrane receptors
G-protein coupled receptors (GPCRs) Cell 169:407-421 (2017)
“How to transmit signals across the membrane?”
Cell surface receptors/channels represent the gateway through which the cell senses and responds to its environment. GPCRs comprise the largest family of transmembrane receptors in humans, and they serve as critical regulators of most aspects of physiology. As a consequence of their profound biological importance, GPCRs have become the most successful target class for therapeutic drug development (1/3 of all FDA-approved drugs). GPCR research has seen major advances in recent years, particularly in terms of studies of receptor structure, dynamics, and pharmacology. Nonetheless, many major aspects of GPCR signaling remain incompletely characterized, and it has become increasingly clear that GPCRs possess an unexpectedly rich and complex signaling biology that is only beginning to be fully understood. We are also interested in molecular mechanisms of membrane channels and their signaling in various cells including neuron. We have established eukaryotic expression systems (human and insect cells) and FSEC (fluorescence size exclusion chromatography) system to express valuable membrane proteins.
Ion channels
Cryo-EM structures of ion channels Acc. Chem. Res. 52:1643-1652 (2019)
“How to transport ions for biological function?”
Ion channels are membrane proteins that are present in the membranes of virtually all living cells. There are hundreds of different ion channels in the human genome, transporting charged ions from one side of a membrane to the other to maintain homeostasis. Many diseases are linked to defects in ion channels, and drugs acting on ion channels have long been used as therapeutics. We are exploring the highly ordered and sophisticated mechanistic mechanism of ion channels by combining cryo-EM, biochemical, and biophysical approaches.