Research

Functional analyses of sugar chains, proteins, and genome in neurological diseases

The Project Leader's Profile

Tatsushi Toda

Professor, Department of Neurology / Molecular Brain Science, Kobe University Graduate School of Medicine
Professor, Division of Clinical Genetics, Department of Medical Genetics, Osaka University Medical School/ Graduate School of Medicine

Dr. Tatsushi Toda is Professor of Neurology / Molecular Brain Science, Kobe University Graduate School of Medicine. He graduated from University of Tokyo in 1985 and entered into Department of Neurology, University of Tokyo. In 1996, he was appointed as Associate professor of Institute of Medical Science, University of Tokyo. In 2000, he was appointed as Professor of Clinical Genetics, Osaka University. From 2009, he holds the current position. He has received Japanese Society of Human Genetics Award, Japan Foundation for Aging and Health Award, Japanese Society of Neurology Award, Asahi Award, and Award from Japanese Minister of Education, Culture, Sports, Science and Technology.

Project Leader
  • Tatsushi Toda, Professor, Department of Neurology / Molecular Brain Science, Kobe University Graduate School of Medicine. Professor, Division of Clinical Genetics, Department of Medical Genetics, Osaka University Medical School/ Graduate School of Medicine
Research Members
  • Kazuhiro Kobayashi, Associate professor, Department of Molecular Brain Science, Kobe University Graduate School of Medicine
  • Motoi Kanagawa, Associate professor, Department of Molecular Brain Science, Kobe University Graduate School of Medicine
  • Mariko Taniguchi-Ikeda, Assistant professor, Division of Pediatrics,  Kobe University Graduate School of Medicine
Research Collaborators
  • Wataru Satake, Assistant Professor, Division of Molecular Brain Science, Kobe University Graduate School of Medicine
  • Atsushi Kuga, Assistant Professor, Division of Neurology, Kobe University Graduate School of Medicine
  • Masako Inada,Research fellow, Division of Molecular Brain Science, Kobe University Graduate School of Medicine
  • Cha Pei Chieng, COE Research fellow, Osaka University Graduate School of Medicine
  • Masaji Tachikawa, Research fellow, Division of Molecular Brain Science, Kobe University Graduate School of Medicine
  • Tamao Endo, Research Group Leader, Tokyo Metropolitan Institute of Gerontology

Summary

Fukuyama-type congenital muscular dystrophy (FCMD) and muscle-eye-brain (MEB) disease are clinically similar autosomal recessive disorders characterized by congenital muscular dystrophy, lissencephaly, and eye anomalies. We identified the gene for FCMD and MEB, which encodes fukutin and POMGnT1. Recent studies have revealed that posttranslational modification of α-dystroglycan is associated with these congenital muscular dystrophies with brain malformations. Parkinson's disease (PD), characterized by loss of dopaminergic neurons, is a multifactorial neurodegenerative disease. By genome wide-approach, we aim to identify susceptibility genes for PD and to establish the tailor-maid therapy. We aim to identify IQ, mental retardation, and autism-related molecules using genetics and DNA chip.

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Some of Recent Papers

  1. Taniguchi-Ikeda M, Kobayashi K, Kanagawa M, Yu CC, Mori K, Oda T, Kuga A, Kurahashi H, Akman HO, DiMauro S, Kaji R, Yokota T, Takeda S, Toda T. Pathogenic exon-trapping by SVA retrotransposon and rescue in Fukuyama muscular dystrophy. Nature 478:127-131, 2011
  2. Satake W, Nakabayashi Y, Mizuta I, Hirota Y, Ito C, Kubo M, Kawaguchi T, Tsunoda T, Watanabe M, Takeda A, Tomiyama H, Nakashima K, Hasegawa K, Obata F, Yoshikawa T, Kawakami H, Sakoda S, Yamamoto M, Hattori N, Murata M, Nakamura Y & Toda T.Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease. Nat Genet 41: 1303-1307, 2009
  3. Sidransky E, Nalls MA, Aasly JO, Aharon-Peretz J, Annesi G, Barbosa ER, Bar-Shira A, Berg D, Bras J, Brice A, Chen CM, Clark LN, Condroyer C, De Marco EV, Durr A, Eblan MJ, Fahn S, Farrer MJ, Fung HC, Gan-Or Z, Gasser T, Gershoni-Baruch R, Giladi N, Griffith A, Gurevich T, Januario C, Kropp P, Lang AE, Lee-Chen GJ, Lesage S, Marder K, Mata IF, Mirelman A, Mitsui J, Mizuta I, Nicoletti G, Oliveira C, Ottman R, Orr-Urtreger A, Pereira LV, Quattrone A, Rogaeva E, Rolfs A, Rosenbaum H, Rozenberg R, Samii A, Samaddar T, Schulte C, Sharma M, Singleton A, Spitz M, Tan EK, Tayebi N, Toda T, Troiano AR, Tsuji S, Wittstock M, Wolfsberg TG, Wu YR, Zabetian CP, Zhao Y, Ziegler SG. Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease. N Engl J Med 361:1651-1661, 2009
  4. Kanagawa M, Nishimoto A, Chiyonobu T, Takeda S, Miyagoe-Suzuki Y, Wang F, Fujikake N, Taniguchi M, Lu Z, Tachikawa M, Nagai Y, Tashiro F, Miyazaki J, Tajima Y, Takeda S, Endo T, Kobayashi K, Campbell KP, and Toda T. Residual laminin-binding activity and enhanced dystroglycan glycosylation in novel model mice to dystroglycanopathy. Hum. Mol. Genet., 18:621-631, 2009.
  5. Fujikake N, Nagai Y, Popiel HA, Okamoto Y, Yamaguchi M, and Toda T. Heat shock transcription factor 1 (HSF1)-activating compounds suppress polyglutamine-induced neurodegeneration through induction of multiple molecular chaperones. J. Biol. Chem., 283, 26188-26197, 2008.
  6. Kano H, Kurahashi H, and Toda T. Genetically regulated epigenetic transcriptional activation of retrotransposon insertion confers mouse dactylaplasia phenotype. Proc, Natl. Acad. Sci. USA, 104, 19034-19039, 2007.
  7. Nagai Y, Inui T, Popiel HA, Fujikake N, Hasegawa K, Urade Y, Goto Y, Naiki H, and Toda T. A toxic monomeric conformer of the polyglutamine protein. Nat. Struct. Mol. Biol., 14, 332-340, 2007.
  8. Taniguchi M, Kurahashi H, Noguchi S, Fukudome T, Okinaga T, Tsukahara T, Tajima Y, Ozono K, Nishino I, Nonaka I, and Toda T. Aberrant neuromuscular junctions and delayed terminal muscle fiber maturation in a-dystroglycanopathies. Hum. Mol. Genet., 15, 1279-1289, 2006.
  9. Mizuta I, Satake W, Nakabayashi Y, Ito C, Suzuki S, Momose Y, Nagai Y, Oka A, Inoko H, Fukae J, Saito Y, Sawabe M, Murayama S, Yamamoto M, Hattori N, Murata M, and Toda T. Multiple candidate gene analysis identifies a-synuclein as a susceptibility gene for sporadic Parkinson's disease. Hum. Mol. Genet., 15, 1151-1158, 2006.