Professor, Section of Neurobiology
Department of Biological Sciences
- Synaptic structure, function, formation, repair, and maintenance.
- Synapse-glia interactions at the neuromuscular junction.
- Cellular and molecular mechanisms of the pathogenesis of Spinal Muscular Atrophy (SMA).
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. We are studying the possible contribution of motor circuit defects to the pathogenesis of SMA, as well as the role of different cell types in SMA disease mechanisms. In addition, we are interested in translational research, and our pre-clinical research helped develop Evrysdi (risdiplam), the first oral drug approved by the FDA in 2020 for treating SMA patients.
I co-edited a 2016 book entitled ?Spinal Muscular Atrophy: Disease Mechanisms and Therapy.?
Department of Biological Sciences
3641 Watt Way HNB 209
Los Angeles, CA 90089-2520
- 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.
Selected PublicationsView a complete PubMed searchView a complete Google Scholar search
- Ichida JK, Ko CP. Organoids Develop Motor Skills: 3D Human Neuromuscular Junctions. Cell Stem Cell. 2020 Feb 6;26(2):131-133. doi: 10.1016/j.stem.2020.01.003. PubMed PMID: 32032521. PubMed Link
- Muscle-specific SMN reduction reveals motor neuronâindependent disease in spinal muscular atrophy models Jeong-Ki Kim, â¦ , Chien-Ping Ko, Umrao R. Monani J Clin Invest. 2020. https://doi.org/10.1172/JCI131989 PubMed Link
- Rimer M, Seaberg BL, Yen PF, Lam S, Hastings RL, Lee YI, Thompson WJ, Feng Z, Metzger F, Paushkin S, Ko CP. Nerve sprouting capacity in a pharmacologically induced mouse model of spinal muscular atrophy. Sci Rep. 2019 May 24;9(1):7799. doi: 10.1038/s41598-019-44222-2. PubMed PMID: 31127156; PubMed Central PMCID: PMC6534600. PubMed Link
- Ratni H., Ebeling M., Baird J., Bendels S., Bylund J., Chen K.S., Denk N., Feng Z., Green L., Guerard M., Jablonski P., Jacobsen B., Khwaja O., Kletzl H., Ko C.-P., Kustermann S., Marquet A., Metzger F., Mueller B., Naryshkin N.A., Paushkin S.V., Pinard E., Poirier A., Reutlinger M., Weetall M., Zeller A., Zhao X., Mueller L. (2018) Discovery of Risdiplam, a Selective Survival of Motor Neuron-2 (SMN2) Gene Splicing Modifier for the Treatment of Spinal Muscular Atrophy (SMA). Journal of Medicine Chemistry, 61:6501-6517. PubMed Link
- Zhao X., Feng Z., Ling, K. K. Y., Mollin A., Sheedy J., Yeh S., Petruska J., Narasimhan J., Dakka A., Welch E., Karp G., Chen K.S., Metzger F., Ratni H., Lotti F., Tisdale S., Naryshkin N.N., Pellizzoni L., Paushkin S., Ko C.-P.*, Weetall M.* (2016) Pharmacokinetics, Pharmacodynamics and Efficacy of a Small Molecule SMN2 Splicing Modifier in Mouse Models of Spinal Muscular Atrophy (*equal co-corresponding authors). Human Molecular Genetics, Feb 29. pii: ddw062. [Epub ahead of print] PubMed PubMed Link
- Zhou C, Feng Z, Ko CP. (2016) Defects in Motoneuron-Astrocyte Interactions in Spinal Muscular Atrophy. J Neurosci. 2016 Feb 24;36(8):2543-53. doi: 10.1523/JNEUROSCI.3534-15.2016. PubMed Link
- Feng Z, Ling KK, Zhao X, Zhou C, Karp G, Welch EM, Naryshkin N, Ratni H, Chen KS, Metzger F, Paushkin S, Weetall M*, Ko, C-P* (2016) Pharmacologically induced mouse model of adult spinal muscular atrophy to evaluate effectiveness of therapeutics after disease onset. (*equal co-corresponding authors). Hum Mol Genet. 2016 Mar 1;25(5):964-75. doi: 10.1093/hmg/ddv629. Epub 2016 Jan 11. PubMed Link
Naryshkin N.A. et al., (2014) SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy. Science 345:688-693. (Recommended by Faculty of 1000 Prime)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
- 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 (Recommended by Faculty of 1000 Prime) PubMed 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