Our aim is to elucidate the pathological cascades for epilepsy, autism and intellectual disability by identifying and analyzing the responsible genes.

Kazuhiro Yamakawa

Kazuhiro Yamakawa, Ph.D.

Team Leader, Neurogenetics
kazuhiro.yamakawa [at] riken.jp

Research Overview

The objective of our laboratory is to understand the molecular pathomechanisms of neurological diseases including epilepsy, autism, and mental retardation, and to develop diagnostic methods and therapies for those diseases. To do this, we are identifying and characterizing the genes responsible for those diseases by suing more than 4000 patients' materials, developing animal disease models, and testing therapeutic methodologies including gene therapy. The epilepsy project includes juvenile myoclonic epilepsy and sodium channelopathy such as generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy in infancy (SMEI) that associates with severe mental decline. We also analyzing cases with epilepsy associated with autism by using full genome analyses. The mental retardation project includes Down syndrome that is the most frequent mental retardation and is caused by trisomy 21. We are characterizing partial trisomy 16 mice as DS animal models, analyzing histological, immunohistochemical, biochemical, behavioral abnormalities and testing potential therapies.

Main Research Field

Related Research Fields


Selected Publications

  1. Bailey JN+, de Nijis L+, Bai D+, Suzuki T+, Miyamoto H, Tanaka M, Patterson C, Lin YC, Medina M, Alonso M, Seratossa J, Duron R, Nguyen V, Wight J, Martinez-Juarez I, Ochoa A, Jara-Prado A, Guilhoto L, Molina Y, Yacubian E, Lopez-Ruiz M, Inoue Y, Kaneko S, Hirose S, Osawa M, Oguni H, Fujimoto S,Grisar T, Stern J, Yamakawa K*, Laykaye B*, Delgado-Escueta A* (+co-firstauthors, and *co-corresponding authors).:
    "Variant intestinal cell kinase in juvenile myoclonic epilepsy"
    New Eng J Med , 378, 1018-28 (2018).
  2. Tatsukawa T, Ogiwara I, Mazaki E, Shimohata A, and Yamakawa K.:
    "Impairments in social novelty recognition and spatial memory in mice with conditional deletion of Scn1a in parvalbumin-expressing cells"
    Neurobiol Dis, 112, 24-34 (2018).
  3. Raveau M, Shimohata A, Amano K, Miyamoto H, and Yamakawa K.:
    "DYRK1A-haploinsufficiency in mice causes autistic-like features and febrile seizures"
    Neurobiol Dis, 110, 180-191 (2017).
  4. Miyamoto H, Shimohata A, Abe M, Abe T, Mazaki M, Amano K, Suzuki T, Tatsukawa T, Itohara S, Sakimura K, and Yamakawa K.:
    "Potentiation of excitatory synaptic transmission ameliorates aggression in mice with Stxbp1 haploinsufficiency"
    Human Molecular Genetics, 26, 4961-4974 (2017).
  5. Raveau M, Nakahari T, Asada S, Ishihara K, Amano K, Shimohata A, Sago H,and Yamakawa K.:
    "Brain ventriculomegaly in Down syndrome mice is caused by Pcp4 dose-dependent cilia dysfunction"
    Hum Mol Genet, 26, 923-931 (2017).
  6. Ogiwara I, Iwasato T, Miyamoto H, Iwata R, Yamagata T, Mazaki E, YanagawaY, Tamamaki N, Hensch TK, Itohara S, and Yamakawa K.:
    "Nav1.1 haploinsufficiency in excitatory neurons ameliorates seizure-associated sudden death in a mouse model of Dravet syndrome."
    Hum Mol Genet, 22(23), 4784-4804 (2013).
  7. Ogiwara I, Miyamoto H, Morita N, Atapour N, Mazaki E, Inoue I, Takeuchi T, Itohara S, Yanagawa Y, Obata K, Furuichi T, Hensch TK, and Yamakawa K.:
    "Nav1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in mice carrying an Scn1a gene mutation."
    J Neurosci, 27(22), 5903-14 (2007).
  8. Suzuki T, Delgado-Escueta AV, Aguan K, Alonso ME, Shi J, Hara Y, Nishida M, Numata T, Medina MT, Takeuchi T, Morita R, Bai D, Ganesh S, Sugimoto Y, Inazawa J, Bailey JN, Ochoa A, Jara-Prado A, Rasmussen A, Ramos-Peek J, Cordova S, Rubio-Donnadieu F, Inoue Y, Osawa M, Kaneko S, Oguni H, Mori Y, and Yamakawa K.:
    "Mutations in EFHC1 cause juvenile myoclonic epilepsy."
    Nat Genet, 36(8), 842-9 (2004).
  9. Kamiya K, Kaneda M, Sugawara T, Mazaki E, Okamura N, Montal M, Makita N,Tanaka M, Fukushima K, Fujiwara T, Inoue Y, and Yamakawa K.:
    "A nonsense mutation of the sodium channel gene SCN2A in a patient with intractable epilepsy and mental decline."
    J Neurosci, 24(11), 2690-2698 (2004).
  10. Sugawara T, Tsurubuchi Y, Agarwala KL, Ito M, Fukuma G, Mazaki-Miyazaki E, Nagafuji H, Noda M, Imoto K, Wada K, Mitsudome A, Kaneko S, Montal M,Nagata K, Hirose S, and Yamakawa K.:
    "A missense mutation of the Na+ channel alpha II subunit gene Na(v)1.2 in a patient with febrile and afebrile seizures causes channel dysfunction."
    Proc Natl Acad Sci U S A, 98(11), 6384-9 (2001).

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