My laboratory studies the mechanism and function of neuronal electrical signaling in health and disease.
Action potentials propagating along axons play a central role in rapid cell-to-cell communication over long distances in the nervous system. Action potential initiation and propagation minimally require sequential activation of voltage-gated Na+ (Nav) and K+ (Kv) channels, as discovered by Hodgkin and Huxley in the 1950s. The genes for these channels started to be cloned in the 1980s. Building on those early structure-function studies, our recent studies have contributed to a better understanding of the mechanisms underlying axonal transport and targeting of both Nav and Kv channels in axons.
Our studies identified the axonal targeting motifs and mechanisms governing polarized axon-dendrite targeting of Kv1 and Kv3 channels, the two major Kv channel subfamilies whose members are present and operate in axons. Although these channel proteins are transported by different kinesin molecular motors, both Kv1 and Kv3 require proper channel assembly through the N-terminal T1 domain for axonal transport. This appears to be a conserved quality-control mechanism by which a neuron ensures that only properly assembled and functioning channel proteins are transported into its axons. By contrast, axonal transport of Nav channels is likely mediated by a distinct group of kinesin motors through ankyrin adaptor proteins. Importantly, we showed that axonal membrane targeting of Kv3.1, especially close to the axon initial segment, can further increase the maximal firing frequency of action potentials in neurons. These results may contribute to a better understanding of a novel form of neuronal plasticity via changes of polarized targeting of key membrane proteins.
Currently, we are focusing on understanding ion channel regulation relevant to several brain disorders, including multiple sclerosis, schizophrenia, epilepsy, concussive brain injury, etc.
Education and Training
PhD - The University of Colorado Health Sciences Center
Post Doctoral - The University of California, San Francisco
Office: 182 Rightmire Hall
Lab: 138 Rightmire Hall