Professor, Section of Neurobiology
Department of Biological Sciences
Editorial Board, Neuron Glia Biology
Phone: (213) 740-9182
University of Southern California
Department of Biological Sciences
3641 Watt Way HNB 209
Los Angeles, CA 90089-2520
Section of Neurobiology
- B.S., National Taiwan University, 1970.
- Ph.D., Washington University in St. Louis, 1975.
- Post-Doctoral, University of Colorado Medical Center, 1978.
- Post-Doctoral, National Institutes of Health, 1981.
- Synaptic structure, function, formation, repair, and maintenance.
- Synapse-glia interactions at the neuromuscular junction.
- Cellular and molecular mechanisms of the pathogenesis of motor neuron diseases, such as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS).
Research OverviewAmong the most challenging questions in neurobiology is how synaptic connections form, function, and maintain at the appropriate targets in normal and diseased nervous systems. To address these important questions, we study the neuromuscular junction (NMJ), a model synapse due to its relatively simple morphology and easy accessibility. Using electrophysiological, morphological, and molecular approaches, we examine the role of synaptic molecules in transmitter release and synaptic plasticity in knockout mice that lack certain genes. We are also interested in the role of glial cells and glial-derived factors in the maintenance of synaptic structure and function as well as in promoting synapse development, regeneration, and sprouting. Our research on synapse-glial interactions explores an emerging concept that glial cells tell neurons to build larger, stronger, and more stable synapses.
We also use transgenic mice to study spinal muscular atrophy (SMA), the leading genetic cause of infant mortality characterized by the loss of spinal motor neurons and widespread muscle atrophy. In addition, we use transgenic mice to investigate the mechanisms of amyotrophic lateral sclerosis (ALS, also called Lou Gehrig's disease), a late-onset neurodegenerative disorder characterized by the selective loss of upper and lower motor neurons. We are studying the possible contribution of synapse loss or defects to the pathogenesis of these motor neuron diseases. In addition, we are interested in translational research by testing molecules that could potentially be used to treat these devastating disorders.
Sahashi, K., Ling, K. K. Y., Hua, Y., Wilkinson, J.E., Nomakuchi, T., Rigo, F., Hung, G., Xu, D., Jiang, Y.-P., Lin, R.Z. Ko, C.-P., Bennett, C.F., and Krainer, A.R. (2013) Pathological impact of SMN2 mis-splicing in adult SMA mice. EMBO Molecular Medicine, 5:1-16 -PubMed -Link
Van Meerbeke, J.P., Gibbs, R.M., Plasterer, H.L., Miao, W., Feng, Z., Lin, M.-Y., Rucki, A.A., Wee, C.D., Xia, B., Sharma, S., Jacques, V., Li, D.K., Pellizzoni, L., Rusche, J.R., Ko, C.-P., and Sumner, C.J., (2013) The DcpS inhibitor RG3039 improves motor function in SMA mice. Human Molecular Genetics, May 31. [Epub ahead of print] -PubMed -Link
Cobb, M.S., Rose, F.F., Rindt, H., Glascock, J.J., Shababi, M., Miller, M.R., Osman, E.Y., Yen, P.-F., Martin, B.R., Wetz, M. J., Mazzasette, C., Feng, Z., Ko, C.-P. and Lorson, C.L. (2013) Development and characterization of an SMN2-based intermediate mouse model of spinal muscular atrophy. Human Molecular Genetics, 22:1843-1855. -PubMed -Link
Lin, M.-Y., Rohan, J.G., Cai, H., Reim, K., Ko, C.-P.* and Chow, R. H.-P.* (2013) Complexin facilitates exocytosis and synchronizes vesicle release in two secretory model systems. (*equal co-corresponding authors) J. Physiology, 591.10, 2463-2473. -PubMed -Link
Sahashi, K., Hua, Y., Ling, K. K. Y., Hung, G., Rigo, F., Horev, G., Masahisa, K., Gen, S., Ko, C.-P., Bennett, C.F., and Krainer, A.R. (2012) TSUNAMI: an antisense method to phenocopy splicing-associated diseases in animals. Genes & Development, 15;26(16):1874-84. -PubMed -Link
Osborne, M., Cirillo, K., Feng, Z., El-Khodor, B., Gomez, D., McEwen, C., Beltran, J., Ghavami, A., Lin, M.-Y., Li, Y., Knowlton, W.M., McKemy, D.D., Martens, K., Davis, C., Doty, R., Wardwell, K., Ko, C.-P., Ramboz, S., Lutz, C. (2012) Characterization of behavioral and neuromuscular junction phenotypes in a novel allelic series of SMA mouse models. Human Molecular Genetics, Epub ahead of print on July 16. Oct 15;21(20):4431-47. -PubMed -Link
Yoo, Y.-E. and Ko, C-.P. (2012) Dihydrotestosterone ameliorates degeneration in muscle, axons and motoneurons and improves motor function in a mouse model of amyotrophic lateral sclerosis. PLoS ONE, 7(5): e37258. doi:10.1371/journal.pone.0037258 -PubMed -Link
Ling, K. K. Y., Gibbs, R.M., Feng, Z., and Ko, C.-P. (2012) Severe neuromuscular denervation of clinically relevant muscles in a mouse model of spinal muscular atrophy. Human Molecular Genetics, 21:185-195; ddr453 first published online October 13, 2011. -PubMed -Link
Yoo, Y.-E. and Ko, C-.P. (2011) Treatment with trichostatin A initiated after disease onset delays disease progression and increases survival in a mouse model of amyotrophic lateral sclerosis. Experimental Neurology, 231:147-159 (Highlighted in a news story by the Alzheimer Research Forum, http://www.alzforum.org/new/detail.asp?id=2836 and by the MDA, http://alsn.mda.org/news/inhibitor-molecule-helps-als-mice-be-stronger-live-longer; also comment in Exp Neurol. 2012 Jan;233(1):112-7) -PubMed -Link
Ling, K.K.Y., Lin, M.-Y., Zingg, B., Feng, Z. and Ko, C.-P. (2010) Synaptic Defects in the Spinal and Neuromuscular Circuitry in a Mouse Model of Spinal Muscular Atrophy. PLoS ONE 5(11): e15457. doi:10.1371/journal.pone.0015457 -PubMed -Link
An, M., Lin, W., Yang J., Dominguez, B., Padgett, D., Sugiura, Y., Aryal, P., Gould, T.W., Oppenheim, R.W., Hester, M.E., Kaspar, B.K., Ko, C.-P., and Lee, K.-F. (2010) Acetylcholine negatively regulates development of the neuromuscular junction through distinct cellular mechanisms. PNAS, 107: 10702-10707. (Recommended by Faculty of 1000 Biology) -PubMed -Link
Feng, Z. and Ko, C.-P. (2008) Schwann cells promote synaptogenesis at the neuromuscular junction via transforming growth factor-beta1. The Journal of Neuroscience, 28:9599-609. (Highlighted in This Week in The Journal, and Recommended by Faculty of 1000 Biology) -PubMed -Link
Ko, C.-P. and Thompson, W. J. (2003) We edited the special issue, The Neuromuscular Junction, in tribute to Sir Bernard Katz. Journal of Neurocytology, 32: 421- 1037. -Link
Reddy, L. V., Koirala, S., Sugiura, Y., Herrera, A. A., and Ko, C.-P. (2003) Glial cells maintain synaptic structure and function and promote development of the neuromuscular junction in vivo. Neuron, 40:563-580. (Recommended by Faculty of 1000 Biology) -PubMed -Link