Our research focuses on the molecular mechanism of membrane channels, receptors, and transporters. We have been using solution NMR spectroscopy to study these proteins, while pushing the technological envelope to enable NMR characterization of the structure and dynamics of more complex membrane systems.

Currently, my lab has three major aspects of research. One aspect is the structure and mechanism of viral ion channels. Our earlier work on influenza proton channels have established a general NMR approach for characterizing the structures of viral channels, and for understanding the structural basis of drug inhibition and drug resistance. The long term goal is to develop novel antiviral therapeutics that target these viral membrane proteins.

Another area involves the function of the transmembrane and membrane proximal regions or domains of receptors in regulating the function of receptors. The membrane-associated regions of cell surface receptors have long been the blind spot in structural biology. We have developed powerful NMR/Biochemistry approach that enabled structure determination of the transmembrane domains of several immunoreceptors. We are developing new technologies to enable the study of conformational coupling between the receptor transmembrane and cytoplasmic domains, which are essential for transmembrane signaling.

Finally, we continue to develop NMR tools and apply them to investigate the dynamic transporters and ion channels that have been difficult to crystalize. In particular, we are using spectroscopic techniques to investigate the "dark" states of proteins that are often critical to understanding their function as well as allosteric modulation of protein function by ligands and substrates. It has been a long struggle for us to develop and apply NMR to tackle difficult membrane proteins. But our laboratory has shown numerous times already that we can use the versatile NMR technology to answer questions for membrane proteins that are either too dynamic to crystalize or too small to be seen by cryoEM at high resolution.


©2005 Chou Research Group