Chien-Ping Ko

Professor Emeritus of Biological Sciences
Email cko@usc.edu

Education

  • Ph.D. Physiology, Washington University, St. Louis, Missouri, 5/1975
  • B.S. Zoology, National Taiwan University, Tawain, 5/1970
    • Postdoctoral Fellow, NINDS, National Institutes of Health, 1978-1981
    • Postdoctroal Fellow, University of Colorado Medical Center, 1975-1978
  • Tenure Track Appointments

    • Professor, University of Southern California, Fall 1996
    • Associate Professor, University of Southern California, Fall 1987
    • Assistant Professor, University of Southern California, Spring 1981
  • Summary Statement of Research Interests

    Among 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.

    https://www.fda.gov/news-events/press-announcements/fda-approves-oral-treatment-spinal-muscular-atrophy#:~:text=The%20U.S.%20Food%20and%20Drug,approved%20to%20treat%20this%20disease.

    Research Keywords

    cellular neurobiology, synapse formation, sprouting, remodeling and maintenance, synaptic transmission, synapse-glial interactions, neuromuscular junction, Schwann cells, amyotrophical lateral sclerosis, spinal muscular atrophy, motor neuron disease

  • Book

    • Sumner, C., Paushkin, S., Ko, CP., (2017). Spinal Muscular Atrophy: Disease Mechanisms and Therapy. (Ko, Chien-Ping, Ed.). San Diego: Academic Press.. LINK

    Book Chapters

    • Feng, Z., Ko, CP., (2009). Schwann Cells and Plasticity of the Neuromuscular Junction. pp. 561-566. Developmental Neurobiology by Academic Press.
    • Ko, CP., , Sugiura, Y., Feng, Z. (2007). The Biology of perisynaptic (terminal) Schwann cells. pp. p.72-99. Cambridge: The Biology of Schwann cells/Cambridge University Press.

    Encyclopedia Article

    • Feng, Z., Ko, CP., (2009). Schwann Cells and Plasticity of the Neuromuscular Junction. (L.R. Squire, Ed.).491-496. Vol. 8 Encyclopedia of Neuroscience. Oxford: Academic Press.
    • Ko, CP., (2001). Neuromuscular System. 10595-10600. Oxford: International Encyclopedia of the Social and Behavioral Sciences.

    Journal Article

    • Zhao, X., Feng, Z., Risher, N., Mollin, A., Sheedy, J., Ling, K., Narasimhan, J., Dakka, A., Baird, J., Ratni, H., Lutz, C., Chen, K., Naryshkin, N., CP, K., Welch, E., Metzger, F., Weetall, M. (2021). SMN protein is required throughout life to prevent spinal muscular atrophy disease progression. Human Molecular Genetics. Advance Access Publication. Vol. 31:1, pp. 82-96. LINK
    • Feng, Z., Lam, S., Tenn, E., Ghosh, A., Cantor, S., Zhang, W., Yen, P., Chen, K., Burden, S., Paushkin, S., Ayalon, G., CP, K. (2021). Activation of Muscle-Specific Kinase (MuSK) Reduces Neuromuscular Defects in the Delta7 Mouse Model of Spinal Muscular Atrophy (SMA). Int. J. Mol. Sci. Vol. 22, 8015 LINK
    • Osman, E. Y., Van, M., Yen, P. F., Lotti, F., Feng, Z., Ling, K. K., Ko, C. P., Pellizzoni, L., Lorson, C. L. (2020). Minor snRNA gene delivery improves the loss of proprioceptive synapses on SMA motor neurons. JCI insight. Vol. 5 (12) PubMed Web Address
    • Kim, J. K., Jha, N. N., Feng, Z., Faleiro, M. R., Chiriboga, C. A., Wei-Lapierre, L., Dirksen, R. T., Ko, C. P., Monani, U. R. (2020). Muscle-specific SMN reduction reveals motor neuron-independent disease in spinal muscular atrophy models. The Journal of clinical investigation. Vol. 130 (3), pp. 1271-1287. PubMed Web Address
    • Ichida, J. K., Ko, C. P. (2020). Organoids Develop Motor Skills: 3D Human Neuromuscular Junctions. Cell stem cell. Vol. 26 (2), pp. 131-133. PubMed Web Address
    • Rimer, M., Seaberg, B. L., Yen, P. F., Lam, S., Hastings, R. L., Lee, Y. I., Thompson, W. J., Feng, Z., Metzger, F., Paushkin, S., Ko, C. P. (2019). Nerve sprouting capacity in a pharmacologically induced mouse model of spinal muscular atrophy. Scientific reports. Vol. 9 (1), pp. 7799. PubMed Web Address
    • Morini, E., Gao, D., Montgomery, C. M., Salani, M., Mazzasette, C., Krussig, T. A., Swain, B., Dietrich, P., Narasimhan, J., Gabbeta, V., Dakka, A., Hedrick, J., Zhao, X., Weetall, M., Naryshkin, N. A., Wojtkiewicz, G. G., Ko, C. P., Talkowski, M. E., Dragatsis, I., Slaugenhaupt, S. A. (2019). ELP1 Splicing Correction Reverses Proprioceptive Sensory Loss in Familial Dysautonomia. American journal of human genetics. Vol. 104 (4), pp. 638-650. PubMed Web Address
    • 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, B. (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 medicinal chemistry. Vol. 61 (15), pp. 6501-6517. PubMed Web Address
    • Osman, E., Washington 3rd, C., Kaifer, K., Mazzasette, C., Patitucci, T., Florea, K., Simon, M., Ko, CP., , Ebert, A., Lorson, C. (2016). Optimization of Morpholino Antisense Oligonucleotides Targeting the Intronic Repressor Element1 in Spinal Muscular Atrophy. Mol Ther. pp. doi: 10.1038/mt.. PubMed Web Address LINK
    • Zhou, C., Feng, Z., Ko, CP., (2016). Defects in Motoneuron-Astrocyte Interactions in Spinal Muscular Atrophy. 2016 Feb 24;36(8):2543-53. doi: 10.1523/JNEUROSCI.3534-15.2016. PubMed Web Address LINK
    • Shababi, M., Feng, Z., Villalon, E., Sibigtroth, C., Osman, E., Miller, M., Williams-Simon, P., Lombardi, A., Sass, T., Atkinson, A., Garcia, M., Ko, CP., , Lorson, C. (2016). Rescue of a Mouse Model of Spinal Muscular Atrophy with Respiratory Distress type 1 (SMARD1) by AAV9-IGHMBP2 is Dose Dependent. Mol Ther. pp. 2016 Feb 10. doi: 10.1038/mt.2016.33.. PubMed Web Address LINK
    • Feng, Z., Ling, K., Zhao, X., Zhou, C., Karp, G., Welch, E., Naryshkin, N., Ratni, H., Chen, K., Metzger, F., Paushkin, S., Weetall, M., Ko, CP., (2016). Pharmacologically induced mouse model of adult spinal muscular atrophy to evaluate effectiveness of therapeutics after disease onset. Hum Mol Genet. pp. 2016 Mar 1;25(5):964-75. doi: 10.1093/hmg/ddv629.. PubMed Web Address LINK
    • Zhao, X., Feng, Z., Ling, K. K., Mollin, A., Sheedy, J., Yeh, S., Petruska, J., Narasimhan, J., Dakka, A., Welch, E. M., Karp, G., Chen, K. S., Metzger, F., Ratni, H., Lotti, F., Tisdale, S., Naryshkin, N. A., 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. Human molecular genetics. Vol. 25 (10), pp. 1885-1899. PubMed Web Address
    • Rindt, H., Feng, Z., Mazzasette, C., Glascock, J., Valdivia, D., Pyles, N., Crawford, T., Swoboda, K., Patitucci, T., Ebert, A., Sumner, C., Ko, CP., , Lorson, C. (2015). Astrocytes influence the severity of spinal muscular atrophy. Hum Mol Genet. pp. 2015 24(14):4094-102 doi: 10.1093/hmg/ddv148. Epub. PubMed Web Address LINK
    • Miller, N., Feng, Z., Edens, B., Yang, B., Shi, H., Sze, C., Hong, B., Su, S., Cantu, J., Topczewski, J., Crawford, T., Ko, C., Sumner, C., Ma, L., Ma, Y. Non-aggregating tau phosphorylation by cyclin-dependent kinase 5 contributes to motor neuron degeneration in spinal muscular atrophy. Non-aggregating tau phosphorylation by cyclin-dependent kinase 5 contributes to motor neuron degeneration in spinal muscular atrophy. , The Journal of Neuroscience2015; Vol. 35(15): 6038-50. PubMed Web Address LINK
    • Ko, CP., , Robitaille, R. (2015). Perisynaptic Schwann cells at the neuromuscular synapse: adaptable, multitasking glial cells. Cold Spring Harbor Perspectives in Biology. pp. 237-255. PubMed Web Address LINK
    • Naryshkin, N. A., et, a. l. (2014). SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy. Science. Vol. 345, pp. 688-693. (Recommended by Faculty of 1000 Prime). PubMed Web Address LINK
    • Sahashi, K., Ling, K. K., 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., Krainer, A. R. (2013). Pathological impact of SMN2 mis-splicing in adult SMA mice. EMBO molecular medicine. Vol. 5 (10), pp. 1586-601. PubMed Web Address
    • Van, 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., Sumner, C. J. (2013). The DcpS inhibitor RG3039 improves motor function in SMA mice. Human molecular genetics. Vol. 22 (20), pp. 4074-83. PubMed Web Address
    • Lin, M. Y., Rohan, J. G., Cai, H., Reim, K., Ko, C. P., Chow,Lin, R. H., Rohan, J. G., Cai, H., Reim, K., Ko, C. P., Chow, R. H. (2013). Complexin facilitates exocytosis and synchronizes vesicle release in two secretory model systems. The Journal of physiology. Vol. 591 (10), pp. 2463-73. PubMed Web Address
    • Cobb, M. S., Rose, F. F., Rindt, H., Glascock, J. J., Shababi, M., Miller, M. R., Osman, E. Y., Yen, P. F., Garcia, M. L., Martin, B. R., Wetz, M. J., Mazzasette, C., Feng, Z., Ko, C. P., Lorson, C. L. (2013). Development and characterization of an SMN2-based intermediate mouse model of Spinal Muscular Atrophy. Human molecular genetics. Vol. 22 (9), pp. 1843-55. PubMed Web Address
    • Ling, K. K., Gibbs, R. M., Feng, Z., Ko, CP., (2012). Severe neuromuscular denervation of clinically relevant muscles in a mouse model of spinal muscular atrophy. Human Molecular Genetics. Vol. 21, pp. 185-195; ddr453 first published online October. PubMed Web Address LINK
    • Sahashi, K., Hua, Y., Ling, K. K., Hung, G., Rigo, F., Horev, G., Katsuno, M., Sobue, G., Ko, C. P., Bennett, C. F., Krainer, A. R. (2012). TSUNAMI: an antisense method to phenocopy splicing-associated diseases in animals. Genes & development. Vol. 26 (16), pp. 1874-84. PubMed Web Address
    • Osborne, M., Gomez, D., Feng, Z., McEwen, C., Beltran, J., Cirillo, K., El-Khodor, B., Lin, M. Y., Li, Y., Knowlton, W. M., McKemy, D. D., Bogdanik, L., Butts-Dehm, K., Martens, K., Davis, C., Doty, R., Wardwell, K., Ghavami, A., Kobayashi, D., 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. Vol. 21 (20), pp. 4431-47. PubMed Web Address
    • Yoo, Y. E., Ko,Yoo, C. P., Ko, C. P. (2012). Dihydrotestosterone ameliorates degeneration in muscle, axons and motoneurons and improves motor function in amyotrophic lateral sclerosis model mice. PloS one. Vol. 7 (5), pp. e37258. PubMed Web Address
    • Lin, M., Rohan, J., Reim, K., Brose, N., Ko, CP., , Chow, R. (2011). Complexin Facilitates Exocytosis and Synchronizes Vesicle Release by Coupling Vesicles and Calcium Channels. PNAS.
    • Yoo, Y., Ko, CP., (2011). Dihydrotestosterone ameliorates degeneration in muscle, axons and motoneurons and improves motor function in a mouse model of amyotrophic lateral sclerosis. Experimental Neurology.
    • Sahashi, K., Hua, Y., Ling, K., Hung, G., Rigo, F., Horev, G., Masahisa, K., Gen, S., Ko, CP., , Bennett, C., Krainer, A. (2011). Phenocopying a motor-neuron disease in mice using exon-skipping antisense oligonucleotides. Journal of Clinical Investigation.
    • Yoo, Y., Ko, CP., (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. Vol. 231, pp. 147-159. PubMed Web Address
    • Ling, K., Lin, M., Zingg, B., Feng, Z., Ko, C. (2010). Synaptic Defects in the Spinal and Neuromuscular Circuitry in a Mouse Model of Spinal Muscular Atrophy. (recommended by Faculty of 1000 Biology). PLoS ONE. Vol. 5 (11), pp. e15457. doi:10.1371/journal.pone.0015457. PubMed Web Address
    • 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, CP., , Lee, K. (2010). Acetylcholine negatively regulates development of the neuromuscular junction through distinct cellular mechanisms. (This paper was recommended by Faculty of 1000 Biology). PNAS. Vol. 107, pp. 10702-10707. PubMed Web Address
    • Reddy, L. V., Koirala, S., Sugiura, Y., Herrera, A. A., Ko, CP., (2003). Glial cells maintain synaptic structure and function and promote development of the neuromuscular junction in vivo. (This paper was recommended by Faculty of 1000 Biology). Neuron. Vol. 40, pp. 563-580. PubMed Web Address LINK
    • Ko, Chien-Ping and Thompson, Wesley J. (Ed.). (2003). The Neuromuscular Junction-a Special Issue. Journal of Neurocytology. Vol. 32, pp. 421-1037. LINK
    • NIH/NSF Career Development Award, 1983-1987
  • Administrative Appointments

    • Head, Neurobiology Section, Dept. of Biological Sciences, 08/16/2009 – 08/15/2012
    • Director, Neurobiology PhD Program (BNRO), Dept. of Biological Sciences, 09/2008 – 06/2011
    • Director/Associate Director
      Center of Electron Microscopy and Microanalysis, 1994 – 2009
  • Editorships and Editorial Boards

    • Editorial Board member, Neuron Glia Biology, 2004 – 2011
    • Associate Editor, Brain Cell Biology, 2006 – 2008
    • Associate Editor, Journal of Neurocytology, 2000 – 2005
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