Molecular basis of bioelectricity and related diseases in nervous and cardiovascular systems; ion channel function and modulation; discovery of drugs that target ion channels
Ion channels are the molecular units of electrical activity in all cell types, which underlies important physiological functions such as heart contraction and neural activities. My research interests focus on the mechanisms of conformational changes during channel opening and closing and on the interaction of ion channels with other molecules in the cell. Currently, we use a combination of molecular biology, protein biochemistry, patch clamp techniques, fluorescence spectrometry and kinetic/structural modeling to study two families of potassium channels: 1) The BK type calcium-activated potassium channels, which are important in the control of blood pressure and neurotransmitter release. They are implicated in hypertension and epilepsy; 2) The KCNQ potassium channels that play a key role in neural excitability and the rhythmic control of the heart rate. Defects in the KCNQ channels have been associated with epilepsy, deafness, and severe inherited cardiac arrhythmias. We are interested in how these channels sense cellular signals such as the membrane voltage and intracellular molecules including calcium, PIP2 and ATP to open, how disease-associated mutations alter channel function, and searching for reagents such as small molecules and peptides that modulate these channels and may lead to drugs for the treatment of human diseases associated with these channels.