Cheol-Hee Kim
  • Ph. D.
  • Cheol-Hee Kim
  • Molecular Genetics
  • N11-514
  • Laboratory of Developmental Genetics (N11-514)
  • +82-42-821-5494, 7535
  • zebrakim@cnu.ac.kr

Academic Career

  • Ph. D., 1997, Department of Pharmacology, Osaka University Medical School, Japan

Career

  • Postdoc., 1998-2001, Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, USA

Research Interests

  • Functional study of mental disorder genes

    We are conducting a systematic zebrafish knockout project to validate candidate genes for mental disorders, including autism. Knockout (KO) zebrafish for the Miles-Carpenter syndrome gene (ZC4H2) were created and KO animal exhibited abnormal swimming, defective eye movement and pectoral fin contractures. We observed a striking reduction in GABAergic interneurons. Analysis of cell-type-specific markers showed a specific loss of V2 interneurons in the brain and spinal cord. Loss of function of ZC4H2 thus likely results in altered connectivity of neuronal circuits, infantile spasm and intellectual disability. The second case is related to autism spectrum disorders (ASDs). ASDs comprise a wide range of neurodevelopmental disorders, characterized by deficits in social behavior, along with repetitive behaviors and impaired communication. Though the exact causes for ASD remain poorly understood, genetic mutations resulting in altered gene function have been implicated causally in ASD. Intragenic mutations in DYRK1A, which have been shown previously to be associated with clinical aspects of Down syndrome, have been associated recently with microcephaly and ASD-like symptoms. We provide a case study of an individual with a 21kb microdeletion within the DYRK1A locus, who has both microcephaly and ASD. We show that dyrk1aa KO fish have microcephaly and impaired social interactions through two newly developed behavioral tests: social interaction and shoaling assays. Also, we confirmed that behavior analysis for ASD through our dyrk1aa KO zebrafish is experimentally tractable, and propose these social behavioral assay methods in zebrafish as a tool for the widespread study of ASD candidate genes.

Selected Publication

  • Mapping Molecular Networks Within Clitoria ternatea Linn. Against LPS-Induced Neuroinflammation in Microglial Cells, Molecular Docking and In Vivo Toxicity Assessment in Zebrafish.Pharmaceuticals
  • Disease Modeling of Rare Neurological Disorders in Zebrafish. Int J Mol Sci. 2022
  • Phosphinate-benzoindocyanin fluorescent probe for endogenous mitochondrial peroxynitrite detection in living cells and gallbladder access in inflammatory zebrafish animal models.Spectrochim Acta A Mol Biomol Spectrosc. 2021 .
  • Novel Macrocyclic Peptidomimetics Targeting the Polo-Box Domain of Polo-Like Kinase 1. J Med Chem. 2022
  • The LAMMER Kinase, LkhA, Affects Aspergillus fumigatus Pathogenicity by Modulating Reproduction and Biosynthesis of Cell Wall PAMPs. Front Cell Infect Microbiol. 2021
  • Nanoemulsion of Flavonoid-Enriched Oil Palm (Elaeis guineessis Jacq.) Leaf Extract Enhances Wound Healing in Zebrafish. Phytomedicine Plus
  • 3DM: deep decomposition and deconvolution microscopy for rapid neural activity imaging. Opt Express. 2021
  • Preliminary Insight of Pyrrolylated-Chalcones as New Anti-Methicillin-Resistant Staphylococcus aureus (Anti-MRSA) Agents. Molecules. 2021
  • Zebrafish Bioassay for Screening Therapeutic Candidates Based on Melanotrophic Activity. Int J Mol Sci. 2021
  • Optogenetic Manipulation of Olfactory Responses in Transgenic Zebrafish: A Neurobiological and Behavioral Study. Int J Mol Sci. 2021
  • A water-soluble boronate masked benzoindocyanin fluorescent probe for the dynamic detection of endogenous mitochondrial peroxynitrite in live cells and zebrafish as inflammation models. Dyes and Pigments. 2021
  • Acute ethanol induces behavioral changes and alters c-fos expression in specific brain regions, including the mammillary body, in zebrafish. Prog Neuropsychopharmacol Biol Psychiatry. 2021
  • Eif2b3 mutants recapitulate phenotypes of vanishing white matter disease and validate novel disease alleles in zebrafish. Hum Mol Genet. 2021
  • Regulation of habenular G protein gamma 8 on learning and memory via modulation of the central acetylcholine system. Molecular Psychiatry. 2020
  • Mutations in FAM50A suggest that Armfield XLID syndrome is a spliceosomopathy. Nat Commun. 2020
  • Disruption of PHF21A causes syndromic intellectual disability with craniofacial anomalies, epilepsy, hypotonia, and neurobehavioral problems including autism. Mol Autism. 2019
  • Reciprocal control of excitatory synapse numbers by Wnt and novel Wnt inhibitor PRR7 secreted on exosomes. Nat Commun. 2018
  • Rnf220 cooperates with Zc4h2 to specify spinal progenitor domains. Development. 2018
  • Targeted knockout of a chemokine-like gene increases anxiety and fear responses. PNAS. 2018
  • Ottogi inhibits Wnt/β-catenin signaling by regulating cell membrane trafficking of Frizzled8. Sci Rep. 2017
  • Zebrafish knockout of Down syndrome gene, DYRK1A, shows social impairments relevant to autism. Mol Autism. 2017
  • Optogenetic control of endogenous Ca(2+) channels in vivo. Nat Biotechnol. 2015
  • ZC4H2, an XLID gene, is required for the generation of a specific subset of CNS interneurons. Hum Mol Genet. 2015
  • The MST1/2-SAV1 complex of the Hippo pathway promotes ciliogenesis. Nat Commun. 2014
  • Highly efficient gene knockout in mice and zebrafish with RNA-guided endonucleases. Genome Res. 2014
  • CCDC41 is required for ciliary vesicle docking to the mother centriole. PNAS. 2013
  • Evolution of the tbx6/16 subfamily genes in vertebrates: insights from zebrafish. Mol Biol Evol. 2012
  • Inhibition of MKK7-JNK Contributes to Resistance of HCC cells to TRAIL-Induced Apoptosis. Gastroenterology. 2012
  • PHF21A in the Potocki-Shaffer syndrome causes intellectual disability and craniofacial anomalies. Am J Hum Genet. 2012.
  • Mind Bomb Is a Ubiquitin Ligase that Is Essential for Activation of Notch Signaling. Developmental Cell. 2003
  • Repressor activity of Headless/Tcf3 is essential for vertebrate head formation. Nature. 2000