Faculty Detail / 研究室詳細

Kazuhiro Yamakawa, Ph.D.

- Our aim is to elucidate the pathological cascades for epilepsy and Down Syndrome by identifying the responsible genes.


Senior Team Leader (Tenured-professor)

Gene, Mutations, Epilepsy, Down syndrome

Kazuhiro  Yamakawa

Research Area

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.

Selected Publications View All

  1. 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-first authors, and *co-corresponding authors): "Variant intestinal cell kinase in juvenile myoclonic epilepsy", New Eng J Med , 378, 1018-28 (2018)

  2. 2

    Raveau M, Polygalov D, Boehringer R, Amano K, Yamakawa K*, and McHugh TJ* (*co-corresponding authors).: "Alterations of in vivo CA1 network activity in Dp(16)1Yey Down
syndrome model mice", eLife, 7, e31543 (2018)

  3. 3

    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)

  4. 4

    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)

  5. 5

    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)

  6. 6

    Shimohata A, Ishihara K, Hattori S, Miyamoto H, Morishita H, Ornthanalai G, Raveau M, Ebrahim AS, Amano K, Yamada K, Sago H, Akiba S, Mataga N, Murphy NP, Miyakawa T, and Yamakawa K. : "Ts1Cje Down syndrome model mice exhibit environmental stimuli-triggered locomotor hyperactivity and sociability concurrent with increased flux through central dopamine and serotonin metabolism", Exp Neurol, 293, 1-12 (2017)

  7. 7

    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)

  8. 8

    Ogiwara I, Iwasato T, Miyamoto H, Iwata R, Yamagata T, Mazaki E, Yanagawa Y, 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)

  9. 9

    Ishihara K, Amano K, Takaki E, Shimohata A, Sago H, Epstein CJ, and Yamakawa K: "Enlarged brain ventricles and impaired neurogenesis in the Ts1Cje and Ts2Cje mouse models of Down syndrome.", Cereb Cortex, 20(5), 1131-43 (2010)

  10. 10

    Ogiwara I, Ito K, Sawaishi Y, Osaka H, Mazaki E, Inoue I, Montal M, Hashikawa T, Shike T, Fujiwara T, Inoue Y, Kaneda M, and Yamakawa K.: "De novo mutations of voltage-gated sodium channel alphaII gene SCN2A in intractable epilepsies.", Neurology, 73(13), 1046-53 (2009)

  11. 11

    Suzuki T, Miyamoto H, Nakahari T, Inoue I, Suemoto T, Jiang B, Hirota Y, Itohara S, Saido TC, Tsumoto T, Sawamoto K, Hensch TK, Delgado-Escueta AV, and Yamakawa K: "Efhc1 deficiency causes spontaneous myoclonus and increased seizure susceptibility.", Hum Mol Genet, 18(6), 1099-109 (2009)

  12. 12

    Amano K, Fujii M, Arata S, Tojima T, Ogawa M, Morita N, Shimohata A, Furuichi T, Itohara S, Kamiguchi H, Korenberg JR, Arata A, and Yamakawa K: "DSCAM deficiency causes loss of pre-inspiratory neuron synchroneity and perinatal death.", J Neurosci, 29(9), 2984-96 (2009)

  13. 13

    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)

  14. 14

    Shukkur EA, Shimohata A, Akagi T, Yu W, Yamaguchi M, Murayama M, Chui D, Takeuchi T, Amano K, Subramhanya KH, Hashikawa T, Sago H, Epstein CJ, Takashima A, and Yamakawa K: "Mitochondrial dysfunction and tau hyperphosphorylation in Ts1Cje, a mouse model for Down syndrome.", Hum Mol Genet, 15(18), 2752-62 (2006)

  15. 15

    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)

  16. 16

    Amano K, Sago H, Uchikawa C, Suzuki T, Kotliarova SE, Nukina N, Epstein CJ, and Yamakawa K: "Dosage-dependent over-expression of genes in the trisomic region of Ts1Cje mouse model for Down syndrome.", Hum Mol Genet, 13(13), 1333-40 (2004)

  17. 17

    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)

  18. 18

    Fujiwara T, Sugawara T, Mazaki-Miyazaki E, Takahashi Y, Fukushima K, Watanabe M, Hara K, Morikawa T, Yagi K, Yamakawa K*, and Inoue Y* (*co-corresponding authors): "Mutations of sodium channel alpha subunit type 1 (SCN1A) in intractable childhood epilepsies with frequent generalized tonic-clonic seizures.", Brain, 126(Pt 3), 531-46 (2003)

  19. 19

    Ganesh S, Delgado-Escueta AV, Sakamoto T, Avila MR, Machado-Salas J, Hoshii Y, Akagi T, Gomi H, Suzuki T, Amano K, Agarwala KL, Hasegawa Y, Bai DS, Ishihara T, Hashikawa T, Itohara S, Cornford EM, Niki H, and Yamakawa K: "Targeted disruption of the Epm2a gene causes formation of Lafora inclusion bodies, neurodegeneration, ataxia, myoclonus epilepsy and impaired behavioral response in mice.", Hum Mol Genet, 11(11), 1251-62 (2002)

  20. 20

    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)

Press Releases View All