My research interest aims at identifying genes essential for neuromuscular function.  In particular, I rely on the awesome power of C. elegans genetics to identify such genes. My genetic study has led to the identification of a class of mutants exhibiting a defect in a specific aspect of movement.  These mutants tend to bend their head excessively when they are stimulated to move rapidly.  Such a movement phenotype indicates that these mutants have a specific defect uncovered by high neuromuscular activities.  Some of the mutants have mutations in known genes whose human counterparts are associated with neuromuscular or neurological diseases, including muscular dystrophy, cardiomyopathies and dystonia.  The other mutants have mutations in novel genes whose human counterparts thus far has not been linked to human diseases.  Given the identical phenotype of the mutants, the novel genes identified represent candidate genes for neuromuscular genetic diseases.  I am using an integrative approach of genetics, cell biology, and molecular biology to identify and characterize the novel genes.  This C. elegans genetic study will provide us a unique opportunity to identify novel genes responsible for neuromuscular diseases, to understand the molecular function of the identified genes, and to help to explore new therapeutics and diagnostics.  In the future, I am planning to expand the findings in our study to the mouse model system. I also have an interest in how ethanol alters membrane excitability in C. elegans muscle and neural cells.  Alcohol is known to have the excitatory and inhibitory actions in excitable cells.  I found in a genetic study that several mutants exhibit a pronounced excitatory behavior when alcohol is presented.  We hypothesize that the excitatory effect of ethanol is exposed in these mutants because the inhibitory effect of ethanol on the behavior is unmasked by mutations.  I am trying to identify molecules that mediate the excitatory effect as well as the inhibitory effect by applying C. elegan genetics and imaging analysis.

Selected Publications

Kim, H., Rogers, M. J., Richmond, J. E., and McIntire, S. M. (2004). SNF-6 is an acetylcholine transporter interacting with the dystrophin complex in Caenorhabditis elegans. Nature, 430, 891-896

Davies, A. G., Shimomura-Pierce, J. T., Kim, H., VanHoven, M. K, Thiele, T. R. Bonci, A., Bargmann, C. I. and McIntire, S. M. (2003). A central role of BK channel in behavioral responses to ethanol in C. elegans. Cell, 115, 655-666.