Research activity information

• Oct. 2023 国立大学法人神戸大学, 令和5年度 神戸大学学長表彰


• Oct. 2022 国立大学法人神戸大学, 令和4年度 神戸大学学長表彰


• Oct. 2021 国立大学法人神戸大学, 令和3年度 神戸大学学長表彰

  小林千浩


• Oct. 2020 国立大学法人神戸大学, 令和2年度 神戸大学学長表彰

  小林千浩


• Oct. 2019 国立大学法人神戸大学, 令和元年度 神戸大学学長表彰

  小林千浩


• Dec. 2016 日本分子生物学会, 第39回日本分子生物学会年会優秀ポスター賞

  Kobayashi Kazuhiro

  Japan society


• Oct. 2016 国立大学法人神戸大学, 平成28年度 神戸大学学長表彰

  戸田達史, Kobayashi Kazuhiro, 金川基, 池田真理子

  Others

• Interleukin-6 Signaling Blockade Induces Regulatory Plasmablasts in Neuromyelitis Optica Spectrum Disorder.

  Ritsu Akatani, Norio Chihara, Atsushi Hara, Asato Tsuji, Shusuke Koto, Kazuhiro Kobayashi, Tatsushi Toda, Riki Matsumoto

  BACKGROUND AND OBJECTIVES: Interleukin-6 receptor antibodies (IL-6R Abs), including satralizumab, are increasingly used to prevent relapse for neuromyelitis optica spectrum disorder (NMOSD). However, the detailed mechanism of action of this treatment on the lymphocyte phenotype remains unclear. This study focused on B cells in patients with NMOSD, hypothesizing that IL-6R Ab enables B cells to acquire regulatory functions by producing the anti-inflammatory cytokine IL-10. METHODS: Peripheral blood mononuclear cells were stimulated in vitro to induce the expansion of B-cell subsets, double-negative B cells (DNs; CD19+ IgD-, CD27-) and plasmablasts (PBs; CD19+, CD27hi, CD38hi). Whole B cells, DNs, or PBs were isolated after culture with IL-6R Ab, and IL-10 expression was quantified using quantitative PCR and a cytometric bead array. RNA sequencing was performed to identify the marker of regulatory PBs induced by IL-6R Ab. RESULTS: DNs and PBs were observed to expand in patients with NMSOD during the acute attacks. In the in vitro model, IL-6R Ab increased IL-10 expression in B cells. Notably, IL-10 expression increased in PBs but not in DNs. Using RNA sequencing, CD200 was identified as a marker of regulatory PBs among the differentially expressed upregulated genes. CD200+ PBs produced more IL-10 than CD200- PBs. Furthermore, patients with NMOSD who received satralizumab had a higher proportion of CD200+ PBs than patients during the acute attacks. DISCUSSION: Treatment with IL-6 signaling blockade elicited a regulatory phenotype in B cells and PBs. CD200+ PBs may be a marker of treatment responsiveness in the context of NMOSD pathophysiology.

  Ovid Technologies (Wolters Kluwer Health), Jul. 2024, Neurology(R) neuroimmunology & neuroinflammation, 11(4) (4), e200266, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Endogenous reductase activities for the generation of ribitol-phosphate, a CDP-ribitol precursor, in mammals

  Shunsuke Hoshino, Hiroshi Manya, Rieko Imae, Kazuhiro Kobayashi, Motoi Kanagawa, Tamao Endo

  Abstract The core M3 O-mannosyl glycan on α-dystroglycan serves as the binding epitope for extracellular matrix molecules. Defects in core M3 glycans cause congenital muscular dystrophies that are collectively known as dystroglycanopathies. The core M3 glycan contains a tandem D-ribitol-5-phosphate (Rbo5P) structure, which is synthesized by the Rbo5P-transferases fukutin and fukutin-related protein using CDP-ribitol (CDP-Rbo) as a donor substrate. CDP-Rbo is synthesized from CTP and Rbo5P by CDP-Rbo pyrophosphorylase A. However, the Rbo5P biosynthesis pathway has yet to be elucidated in mammals. Here, we investigated the reductase activities toward four substrates, including ribose, ribulose, ribose-phosphate and ribulose-phosphate, to identify the intracellular Rbo5P production pathway and elucidated the role of the aldo-keto reductases AKR1A1, AKR1B1 and AKR1C1 in those pathways. It was shown that the ribose reduction pathway is the endogenous pathway that contributes most to Rbo5P production in HEK293T cells and that AKR1B1 is the major reductase in this pathway.

  Oxford University Press (OUP), Dec. 2023, The Journal of Biochemistry, 175(4) (4), 418 - 425

  [Refereed]

  Scientific journal


• TDP-43 regulates cholesterol biosynthesis by inhibiting sterol regulatory element-binding protein 2

  Naohiro Egawa, Yuishin Izumi, Hidefumi Suzuki, Itaru Tsuge, Koji Fujita, Hitoshi Shimano, Keiichi Izumikawa, Nobuhiro Takahashi, Kayoko Tsukita, Takako Enami, Masahiro Nakamura, Akira Watanabe, Motoko Naitoh, Shigehiko Suzuki, Tsuneyoshi Seki, Kazuhiro Kobayashi, Tatsushi Toda, Ryuji Kaji, Ryosuke Takahashi, Haruhisa Inoue

  Abstract Dyslipidemia is considered an essential component of the pathological process of amyotrophic lateral sclerosis (ALS), a fatal motor neuron disease. Although TAR DNA Binding Protein 43 kDa (TDP-43) links both familial and sporadic forms of ALS and cytoplasmic aggregates are a hallmark of most cases of ALS, the molecular mechanism and the in vivo relation of ALS dyslipidemia with TDP-43 have been unclear. To analyze the dyslipidemia-related gene expression by TDP-43, we performed expression microarray and RNA deep sequencing (RNA-Seq) using cell lines expressing high levels of TDP-43 and identified 434 significantly altered genes including sterol regulatory element-binding protein 2 (SREBP2), a master regulator of cholesterol homeostasis and its downstream genes. Elevated TDP-43 impaired SREBP2 transcriptional activity, leading to inhibition of cholesterol biosynthesis. The amount of cholesterol was significantly decreased in the spinal cords of TDP-43-overexpressed ALS model mice and in the cerebrospinal fluids of ALS patients. These results suggested that TDP-43 could play an essential role in cholesterol biosynthesis in relation to ALS dyslipidemia.

  Springer Science and Business Media LLC, May 2022, Scientific Reports, 12(1) (1), 7988 - 7988

  [Refereed]

  Scientific journal


• Comparative whole transcriptome analysis of Parkinson’s disease focusing on the efficacy of zonisamide

  Tatsuhiko Naito, Wataru Satake, Pei-Chieng Cha, Kazuhiro Kobayashi, Miho Murata, Tatsushi Toda

  Objective Interindividual variations in responsiveness to zonisamide in patients with Parkinson’s disease (PD) have been observed in clinical settings. To decipher the molecular mechanisms determining the efficacy of zonisamide, we conducted whole transcriptome sequencing analysis of patients with PD. Methods We selected 23 super-responders (SRs) and 25 non-responders (NRs) to zonisamide from patients with PD who had participated in a previous clinical trial for the approval of zonisamide for the treatment of ‘wearing-off’. Whole transcriptome analysis of peripheral blood was conducted on samples taken before and 12 weeks after zonisamide treatment. We performed differential gene expression analysis to compare between the SRs and NRs at each time point. Results Differentially expressed genes in the pre-treatment samples were significantly enriched for glutamatergic synapses and insulin-like growth factor binding (P_adj=7.8 × 10⁻³ and 0.029, respectively). The gene sets associated with these functions changed more dynamically by treatment in SRs than NRs (p=7.2 × 10⁻³ and 8.2 × 10⁻³, respectively). Conclusions Our results suggest that the efficacy of zonisamide in PD patients is associated with glutamate-related synaptic modulation and p53-mediated dopaminergic neural loss. Their transcriptomic differences could be captured before treatment, which would lead to the realisation of future personalised treatment.

  BMJ, May 2022, Journal of Neurology, Neurosurgery & Psychiatry, 93(5) (5), 509 - 512

  [Refereed]

  Scientific journal


• CDP-ribitol prodrug treatment ameliorates ISPD-deficient muscular dystrophy mouse model

  Hideki Tokuoka, Rieko Imae, Hitomi Nakashima, Hiroshi Manya, Chiaki Masuda, Shunsuke Hoshino, Kazuhiro Kobayashi, Dirk J. Lefeber, Riki Matsumoto, Takashi Okada, Tamao Endo, Motoi Kanagawa, Tatsushi Toda

  Abstract Ribitol-phosphate modification is crucial for the functional maturation of α-dystroglycan. Its dysfunction is associated with muscular dystrophy, cardiomyopathy, and central nervous system abnormalities; however, no effective treatments are currently available for diseases caused by ribitol-phosphate defects. In this study, we demonstrate that prodrug treatments can ameliorate muscular dystrophy caused by defects in isoprenoid synthase domain containing (ISPD), which encodes an enzyme that synthesizes CDP-ribitol, a donor substrate for ribitol-phosphate modification. We generated skeletal muscle-selective Ispd conditional knockout mice, leading to a pathogenic reduction in CDP-ribitol levels, abnormal glycosylation of α-dystroglycan, and severe muscular dystrophy. Adeno-associated virus-mediated gene replacement experiments suggested that the recovery of CDP-ribitol levels rescues the ISPD-deficient pathology. As a prodrug treatment strategy, we developed a series of membrane-permeable CDP-ribitol derivatives, among which tetraacetylated CDP-ribitol ameliorated the dystrophic pathology. In addition, the prodrug successfully rescued abnormal α-dystroglycan glycosylation in patient fibroblasts. Consequently, our findings provide proof-of-concept for supplementation therapy with CDP-ribitol and could accelerate the development of therapeutic agents for muscular dystrophy and other diseases caused by glycosylation defects.

  Springer Science and Business Media LLC, Apr. 2022, Nature Communications, 13(1) (1), 1847 - 1847

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Genetic Variations and Clinical Spectrum of Dystroglycanopathy in a Large Cohort of Chinese Patients

  Danyu Song, Yi Dai, Xiaoyu Chen, Xiaona Fu, Xingzhi Chang, Ning Wang, Cheng Zhang, Chuanzhu Yan, Hong Zheng, Liwen Wu, Li Jiang, Ying Hua, Haipo Yang, Zhiqiang Wang, Tingjun Dai, Wenhua Zhu, Chunxi Han, Yun Yuan, Kazuhiro Kobayashi, Tatsushi Toda, Hui Xiong

  Wiley, Nov. 2020, Clinical Genetics, 99(3) (3), 384 - 395

  [Refereed]

  Scientific journal


• Galectin 3-binding protein suppresses amyloid-β production by modulating β-cleavage of amyloid precursor protein.

  Tsuneyoshi Seki, Motoi Kanagawa, Kazuhiro Kobayashi, Hisatomo Kowa, Naoki Yahata, Kei Maruyama, Nobuhisa Iwata, Haruhisa Inoue, Tatsushi Toda

  Alzheimer's disease (AD) is the most common type of dementia, and its pathogenesis is associated with accumulation of amyloid-β (Aβ) peptides. Aβ is produced from amyloid precursor protein (APP) that is sequentially cleaved by β- and γ-secretases. Therefore, APP processing has been a target in therapeutic strategies for managing AD; however, no effective treatment of AD patients is currently available. Here, to identify endogenous factors that modulate Aβ production, we performed a gene microarray-based transcriptome analysis of neuronal cells derived from human induced pluripotent stem cells because Aβ production in these cells changes during neuronal differentiation. We found that expression of the glycophosphatidylinositolspecific phospholipase D1 (GPLD1) gene is associated with these changes in Aβ production. GPLD1 overexpression in HEK293 cells increased the secretion of galectin 3-binding protein (GAL3BP), which suppressed Aβ production in an AD model, neuroglioma H4 cells. Mechanistically, GAL3BP suppressed Aβ production by directly interacting with APP and thereby inhibiting APP processing by β-secretase. Furthermore, we show that cells take up extracellularly added GAL3BP via endocytosis and that GAL3BP is localized in close proximity to APP in endosomes where amyloidogenic APP processing takes place. Taken together, our results indicate that GAL3BP may be a suitable target of AD-modifying drugs in future therapeutic strategies for managing AD.

  Jan. 2020, The Journal of biological chemistry, 295(11) (11), 3678 - 3691, English, International magazine

  [Refereed]

  Scientific journal


• Crystal structures of fukutin-related protein (FKRP), a ribitol-phosphate transferase related to muscular dystrophy.

  Naoyuki Kuwabara, Rieko Imae, Hiroshi Manya, Tomohiro Tanaka, Mamoru Mizuno, Hiroki Tsumoto, Motoi Kanagawa, Kazuhiro Kobayashi, Tatsushi Toda, Toshiya Senda, Tamao Endo, Ryuichi Kato

  α-Dystroglycan (α-DG) is a highly-glycosylated surface membrane protein. Defects in the O-mannosyl glycan of α-DG cause dystroglycanopathy, a group of congenital muscular dystrophies. The core M3 O-mannosyl glycan contains tandem ribitol-phosphate (RboP), a characteristic feature first found in mammals. Fukutin and fukutin-related protein (FKRP), whose mutated genes underlie dystroglycanopathy, sequentially transfer RboP from cytidine diphosphate-ribitol (CDP-Rbo) to form a tandem RboP unit in the core M3 glycan. Here, we report a series of crystal structures of FKRP with and without donor (CDP-Rbo) and/or acceptor [RboP-(phospho-)core M3 peptide] substrates. FKRP has N-terminal stem and C-terminal catalytic domains, and forms a tetramer both in crystal and in solution. In the acceptor complex, the phosphate group of RboP is recognized by the catalytic domain of one subunit, and a phosphate group on O-mannose is recognized by the stem domain of another subunit. Structure-based functional studies confirmed that the dimeric structure is essential for FKRP enzymatic activity.

  Jan. 2020, Nature communications, 11(1) (1), 303 - 303, English, International magazine

  [Refereed]

  Scientific journal


• Elimination of fukutin reveals cellular and molecular pathomechanisms in muscular dystrophy-associated heart failure.

  Yoshihiro Ujihara, Motoi Kanagawa, Satoshi Mohri, Satomi Takatsu, Kazuhiro Kobayashi, Tatsushi Toda, Keiji Naruse, Yuki Katanosaka

  Heart failure is the major cause of death for muscular dystrophy patients, however, the molecular pathomechanism remains unknown. Here, we show the detailed molecular pathogenesis of muscular dystrophy-associated cardiomyopathy in mice lacking the fukutin gene (Fktn), the causative gene for Fukuyama muscular dystrophy. Although cardiac Fktn elimination markedly reduced α-dystroglycan glycosylation and dystrophin-glycoprotein complex proteins in sarcolemma at all developmental stages, cardiac dysfunction was observed only in later adulthood, suggesting that membrane fragility is not the sole etiology of cardiac dysfunction. During young adulthood, Fktn-deficient mice were vulnerable to pathological hypertrophic stress with downregulation of Akt and the MEF2-histone deacetylase axis. Acute Fktn elimination caused severe cardiac dysfunction and accelerated mortality with myocyte contractile dysfunction and disordered Golgi-microtubule networks, which were ameliorated with colchicine treatment. These data reveal fukutin is crucial for maintaining myocyte physiology to prevent heart failure, and thus, the results may lead to strategies for therapeutic intervention.

  Dec. 2019, Nature communications, 10(1) (1), 5754 - 5754, English, International magazine

  [Refereed]

  Link to Kobe Univ. Repository (Kernel)


• Psychosocial Twin Cohort Studies in Japan: The Keio Twin Research Center (KoTReC).

  Juko Ando, Keiko K Fujisawa, Kai Hiraishi, Chizuru Shikishima, Tetsuya Kawamoto, Mari Nozaki, Shinji Yamagata, Yusuke Takahashi, Kunitake Suzuki, Yoshiaki Someya, Koken Ozaki, Minako Deno, Mami Tanaka, Shoko Sasaki, Tatsushi Toda, Kazuhiro Kobayashi, Masamichi Sakagami, Mitsuhiro Okada, Nobuhiko Kijima, Ryu Takizawa, Kou Murayama

  The Keio Twin Research Center (KoTReC) was established in 2009 at Keio University to combine two longitudinal cohort projects - the Keio Twin Study (KTS) for adolescence and adulthood and the Tokyo Twin Cohort Project (ToTCoP) for infancy and childhood. KoTReC also conducted a two-time panel study of self-control and psychopathology in twin adolescence in 2012 and 2013 and three independent anonymous cross-sectional twin surveys (ToTcross) before 2012 - the ToTCross, the Junior and Senior High School Survey and the High School Survey. This article introduces the recent research designs of KoTReC and its publications.

  Dec. 2019, Twin research and human genetics : the official journal of the International Society for Twin Studies, 22(6) (6), 591 - 596, English, International magazine

  [Refereed]

  Scientific journal


• Characterization of dystroglycan binding in adhesion of human induced pluripotent stem cells to laminin-511 E8 fragment.

  Yumika Sugawara, Keisuke Hamada, Yuji Yamada, Jun Kumai, Motoi Kanagawa, Kazuhiro Kobayashi, Tatsushi Toda, Yoichi Negishi, Fumihiko Katagiri, Kentaro Hozumi, Motoyoshi Nomizu, Yamato Kikkawa

  Human induced pluripotent stem cells (hiPSCs) grow indefinitely in culture and have the potential to regenerate various tissues. In the development of cell culture systems, a fragment of laminin-511 (LM511-E8) was found to improve the proliferation of stem cells. The adhesion of undifferentiated cells to LM511-E8 is mainly mediated through integrin α6β1. However, the involvement of non-integrin receptors remains unknown in stem cell culture using LM511-E8. Here, we show that dystroglycan (DG) is strongly expressed in hiPSCs. The fully glycosylated DG is functionally active for laminin binding, and although it has been suggested that LM511-E8 lacks DG binding sites, the fragment does weakly bind to DG. We further identified the DG binding sequence in LM511-E8, using synthetic peptides, of which, hE8A5-20 (human laminin α5 2688-2699: KTLPQLLAKLSI) derived from the laminin coiled-coil domain, exhibited DG binding affinity and cell adhesion activity. Deletion and mutation studies show that LLAKLSI is the active core sequence of hE8A5-20, and that, K2696 is a critical amino acid for DG binding. We further demonstrated that hiPSCs adhere to hE8A5-20-conjugated chitosan matrices. The amino acid sequence of DG binding peptides would be useful to design substrata for culture system of undifferentiated and differentiated stem cells.

  Sep. 2019, Scientific reports, 9(1) (1), 13037 - 13037, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Triglyceride deposit cardiomyovasculopathy: a rare cardiovascular disorder.

  Ming Li, Ken-Ichi Hirano, Yoshihiko Ikeda, Masahiro Higashi, Chikako Hashimoto, Bo Zhang, Junji Kozawa, Koichiro Sugimura, Hideyuki Miyauchi, Akira Suzuki, Yasuhiro Hara, Atsuko Takagi, Yasuyuki Ikeda, Kazuhiro Kobayashi, Yoshiaki Futsukaichi, Nobuhiro Zaima, Satoshi Yamaguchi, Rojeet Shrestha, Hiroshi Nakamura, Katsuhiro Kawaguchi, Eiryu Sai, Shu-Ping Hui, Yusuke Nakano, Akinori Sawamura, Tohru Inaba, Yasuhiko Sakata, Yoko Yasui, Yasuyuki Nagasawa, Shintaro Kinugawa, Kazunori Shimada, Sohsuke Yamada, Hiroyuki Hao, Daisaku Nakatani, Tomomi Ide, Tetsuya Amano, Hiroaki Naito, Hironori Nagasaka, Kunihisa Kobayashi

  Triglyceride deposit cardiomyovasculopathy (TGCV) is a phenotype primarily reported in patients carrying genetic mutations in PNPLA2 encoding adipose triglyceride lipase (ATGL) which releases long chain fatty acid (LCFA) as a major energy source by the intracellular TG hydrolysis. These patients suffered from intractable heart failure requiring cardiac transplantation. Moreover, we identified TGCV patients without PNPLA2 mutations based on pathological and clinical studies. We provided the diagnostic criteria, in which TGCV with and without PNPLA2 mutations were designated as primary TGCV (P-TGCV) and idiopathic TGCV (I-TGCV), respectively. We hereby report clinical profiles of TGCV patients. Between 2014 and 2018, 7 P-TGCV and 18 I-TGCV Japanese patients have been registered in the International Registry. Patients with I-TGCV, of which etiologies and causes are not known yet, suffered from adult-onset severe heart disease, including heart failure and coronary artery disease, associated with a marked reduction in ATGL activity and myocardial washout rate of LCFA tracer, as similar to those with P-TGCV. The present first registry-based study showed that TGCV is an intractable, at least at the moment, and heterogeneous cardiovascular disorder.

  Jun. 2019, Orphanet journal of rare diseases, 14(1) (1), 134 - 134, English, International magazine


• Triglyceride Deposit Cardiomyovasculopathy: A Rare Cardiovascular Disorder

  Ming Li, Ken-ichi Hirano, Yoshihiko Ikeda, Masahiro Higashi, Chikako Hashimoto, Bo Zhang, Junji Kozawa, Koichiro Sugimura, Hideyuki Miyauchi, Akira Suzuki, Yasuhiro Hara, Atsuko Takagi, Yasuyuki Ikeda, Kazuhiro Kobayashi, Yoshiaki Futsukaichi, Nobuhiro Zaima, Satoshi Yamaguchi, Shrestha Rojeet, Hiroshi Nakamura, Katsuhiro Kawaguchi, Eiryu Sai, Shu-Ping Hui, Yusuke Nakano, Akinori Sawamura, Tohru Inaba, Yasuhiko Sakata, Yoko Yasui, Yasuyuki Nagasawa, Shintaro Kinugawa, Kazunori Shimada, Sohsuke Yamada, Hiroyuki Hao, Daisaku Nakatani, Tomomi Ide, Tetsuya Amano, Hiroaki Naito, Hironori Nagasaka, Kunihisa Kobayashi, on behalf of, the Japan, TGCV study group

  May 2019, Orphanet Journal of Rare Disease, 14(1) (1), 134 - 134, English

  [Refereed]

  Scientific journal


• Wide distribution of alpha-synuclein oligomers in multiple system atrophy brain detected by proximity ligation.

  Hiroaki Sekiya, Hisatomo Kowa, Hinako Koga, Mariko Takata, Wataru Satake, Naonobu Futamura, Itaru Funakawa, Kenji Jinnai, Motonori Takahashi, Takeshi Kondo, Yasuhiro Ueno, Motoi Kanagawa, Kazuhiro Kobayashi, Tatsushi Toda

  Multiple system atrophy (MSA) is a fatal adult-onset neurodegenerative disease that is characterized by varying degrees of cerebellar dysfunction and Parkinsonism. The neuropathological hallmark of MSA is alpha-synuclein (AS)-positive glial cytoplasmic inclusions (GCIs). Although severe neuronal loss (NL) is also observed in MSA, neuronal inclusions (NIs) are rare compared to GCIs, such that the pathological mechanism of NL in MSA is unclear. GCIs and NIs are late-stage pathology features relative to AS oligomers and may not represent early pathological changes in MSA. To reveal the early pathology of MSA, it is necessary to examine the early aggregation of AS, i.e., AS oligomers. Here, we adopted a proximity ligation assay (PLA) to examine the distribution of AS oligomers in brain tissue samples from patients with MSA and other diseases. Surprisingly, MSA brains showed a widespread distribution and abundant accumulation of oligomeric AS in neurons as well as oligodendrocytes of the neocortex. In several regions, oligomeric AS signal intensity was higher in cases with MSA than in cases with Parkinson's disease. In contrast to previous studies, AS-PLA revealed abundant AS oligomer accumulation in Purkinje cells in MSA brains, identifying oligomeric AS accumulation as a possible cause of Purkinje cell loss. This wide distribution of AS oligomers in MSA brain neurons has not been described previously and indicates a pathological mechanism of NL in MSA.

  Mar. 2019, Acta neuropathologica, 137(3) (3), 455 - 466, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• In silico drug screening by using genome-wide association study data repurposed dabrafenib, an anti-melanoma drug, for Parkinson's disease.

  Takeshi Uenaka, Wataru Satake, Pei-Chieng Cha, Hideki Hayakawa, Kousuke Baba, Shiying Jiang, Kazuhiro Kobayashi, Motoi Kanagawa, Yukinori Okada, Hideki Mochizuki, Tatsushi Toda

  Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron loss. At present, there are no drugs that stop the progression of PD. As with other multifactorial genetic disorders, genome-wide association studies (GWASs) found multiple risk loci for PD, although their clinical significance remains uncertain. Here, we report the identification of candidate drugs for PD by a method using GWAS data and in silico databases. We identified 57 Food and Drug Administration-approved drug families as candidate neuroprotective drugs for PD. Among them, dabrafenib, which is known as a B-Raf kinase inhibitor and is approved for the treatment of malignant melanoma, showed remarkable cytoprotective effects in neurotoxin-treated SH-SY5Y cells and mice. Dabrafenib was found to inhibit apoptosis, and to enhance the phosphorylation of extracellular signal-regulated kinase (ERK), and inhibit the phosphorylation of c-Jun NH2-terminal kinase. Dabrafenib targets B-Raf, and we confirmed a protein-protein interaction between B-Raf and Rit2, which is coded by RIT2, a PD risk gene in Asians and Caucasians. In RIT2-knockout cells, the phosphorylation of ERK was reduced, and dabrafenib treatment improved the ERK phosphorylation. These data indicated that dabrafenib exerts protective effects against neurotoxicity associated with PD. By using animal model, we confirmed the effectiveness of this in silico screening method. Furthermore, our results suggest that this in silico drug screening system is useful in not only neurodegenerative diseases but also other common diseases such as diabetes mellitus and hypertension.

  Nov. 2018, Human molecular genetics, 27(22) (22), 3974 - 3985, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• CDP-glycerol inhibits the synthesis of the functional O-mannosyl glycan of α-dystroglycan.

  Rieko Imae, Hiroshi Manya, Hiroki Tsumoto, Kenji Osumi, Tomohiro Tanaka, Mamoru Mizuno, Motoi Kanagawa, Kazuhiro Kobayashi, Tatsushi Toda, Tamao Endo

  α-Dystroglycan (α-DG) is a highly glycosylated cell-surface laminin receptor. Defects in the O-mannosyl glycan of an α-DG with laminin-binding activity can cause α-dystroglycanopathy, a group of congenital muscular dystrophies. In the biosynthetic pathway of functional O-mannosyl glycan, fukutin (FKTN) and fukutin-related protein (FKRP), whose mutated genes underlie α-dystroglycanopathy, sequentially transfer ribitol phosphate (RboP) from CDP-Rbo to form a tandem RboP unit (RboP-RboP) required for the synthesis of the laminin-binding epitope on O-mannosyl glycan. Both RboP- and glycerol phosphate (GroP)-substituted glycoforms have recently been detected in recombinant α-DG. However, it is unclear how GroP is transferred to the O-mannosyl glycan or whether GroP substitution affects the synthesis of the O-mannosyl glycan. Here, we report that, in addition to having RboP transfer activity, FKTN and FKRP can transfer GroP to O-mannosyl glycans by using CDP-glycerol (CDP-Gro) as a donor substrate. Kinetic experiments indicated that CDP-Gro is a less efficient donor substrate for FKTN than is CDP-Rbo. We also show that the GroP-substituted glycoform synthesized by FKTN does not serve as an acceptor substrate for FKRP and that therefore further elongation of the outer glycan chain cannot occur with this glycoform. Finally, CDP-Gro inhibited the RboP transfer activities of both FKTN and FKRP. These results suggest that CDP-Gro inhibits the synthesis of the functional O-mannosyl glycan of α-DG by preventing further elongation of the glycan chain. This is the first report of GroP transferases in mammals.

  Aug. 2018, The Journal of biological chemistry, 293(31) (31), 12186 - 12198, English, International magazine

  [Refereed]

  Scientific journal


• Two patients with PNKP mutations presenting with microcephaly, seizure, and oculomotor apraxia

  M. Taniguchi-Ikeda, N. Morisada, H. Inagaki, Y. Ouchi, Y. Takami, M. Tachikawa, W. Satake, K. Kobayashi, S. Tsuneishi, S. Takada, H. Yamaguchi, H. Nagase, K. Nozu, N. Okamoto, H. Nishio, T. Toda, I. Morioka, H. Wada, H. Kurahashi, K. Iijima

  Blackwell Publishing Ltd, Apr. 2018, Clinical Genetics, 93(4) (4), 931 - 933, English

  [Refereed]

  Scientific journal


• Temporal requirement of dystroglycan glycosylation during brain development and rescue of severe cortical dysplasia via gene delivery in the fetal stage.

  Atsushi Sudo, Motoi Kanagawa, Mai Kondo, Chiyomi Ito, Kazuhiro Kobayashi, Mitsuharu Endo, Yasuhiro Minami, Atsu Aiba, Tatsushi Toda

  Congenital muscular dystrophies (CMDs) are characterized by progressive weakness and degeneration of skeletal muscle. In several forms of CMD, abnormal glycosylation of α-dystroglycan (α-DG) results in conditions collectively known as dystroglycanopathies, which are associated with central nervous system involvement. We recently demonstrated that fukutin, the gene responsible for Fukuyama congenital muscular dystrophy, encodes the ribitol-phosphate transferase essential for dystroglycan function. Brain pathology in patients with dystroglycanopathy typically includes cobblestone lissencephaly, mental retardation, and refractory epilepsy; however, some patients exhibit average intelligence, with few or almost no structural defects. Currently, there is no effective treatment for dystroglycanopathy, and the mechanisms underlying the generation of this broad clinical spectrum remain unknown. Here, we analysed four distinct mouse models of dystroglycanopathy: two brain-selective fukutin conditional knockout strains (neuronal stem cell-selective Nestin-fukutin-cKO and forebrain-selective Emx1-fukutin-cKO), a FukutinHp strain with the founder retrotransposal insertion in the fukutin gene, and a spontaneous Large-mutant Largemyd strain. These models exhibit variations in the severity of brain pathology, replicating the clinical heterogeneity of dystroglycanopathy. Immunofluorescence analysis of the developing cortex suggested that residual glycosylation of α-DG at embryonic day 13.5 (E13.5), when cortical dysplasia is not yet apparent, may contribute to subsequent phenotypic heterogeneity. Surprisingly, delivery of fukutin or Large into the brains of mice at E12.5 prevented severe brain malformation in Emx1-fukutin-cKO and Largemyd/myd mice, respectively. These findings indicate that spatiotemporal persistence of functionally glycosylated α-DG may be crucial for brain development and modulation of glycosylation during the fetal stage could be a potential therapeutic strategy for dystroglycanopathy.

  Apr. 2018, Human molecular genetics, 27(7) (7), 1174 - 1185, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Cell endogenous activities of fukutin and FKRP coexist with the ribitol xylosyltransferase, TMEM5.

  Ryuta Nishihara, Kazuhiro Kobayashi, Rieko Imae, Hiroki Tsumoto, Hiroshi Manya, Mamoru Mizuno, Motoi Kanagawa, Tamao Endo, Tatsushi Toda

  Dystroglycanopathies are a group of muscular dystrophies that are caused by abnormal glycosylation of dystroglycan; currently 18 causative genes are known. Functions of the dystroglycanopathy genes fukutin, fukutin-related protein (FKRP), and transmembrane protein 5 (TMEM5) were most recently identified; fukutin and FKRP are ribitol-phosphate transferases and TMEM5 is a ribitol xylosyltransferase. In this study, we show that fukutin, FKRP, and TMEM5 form a complex while maintaining each of their enzyme activities. Immunoprecipitation and immunofluorescence experiments demonstrated protein interactions between these 3 proteins. A protein complex consisting of endogenous fukutin and FKRP, and exogenously expressed TMEM5 exerts activities of each enzyme. Our data showed for the first time that endogenous fukutin and FKRP enzyme activities coexist with TMEM5 enzyme activity, and suggest the possibility that formation of this enzyme complex may contribute to specific and prompt biosynthesis of glycans that are required for dystroglycan function.

  Mar. 2018, Biochemical and biophysical research communications, 497(4) (4), 1025 - 1030, English, International magazine

  [Refereed]

  Scientific journal


• Newly developed selective immunoinactivation assay revealed reduction in adipose triglyceride lipase activity in peripheral leucocytes from patients with idiopathic triglyceride deposit cardiomyovasculopathy

  Atsuko Takagi, Yasuyuki Ikeda, Kunihisa Kobayashi, Kazuhiro Kobayashi, Yoshihiko Ikeda, Junji Kozawa, Hideyuki Miyauchi, Ming Li, Chikako Hashimoto, Yasuhiro Hara, Satoshi Yamaguchi, Akira Suzuki, Tatsushi Toda, Hironori Nagasaka, Ken-ichi Hirano

  Elsevier B.V., Jan. 2018, Biochemical and Biophysical Research Communications, 495(1) (1), 646 - 651, English

  [Refereed]

  Scientific journal


• Novel FKRP mutations in a Japanese MDC1C sibship clinically diagnosed with Fukuyama congenital muscular dystrophy

  Mieko Yoshioka, Kazuhiro Kobayashi, Tatsushi Toda

  Nov. 2017, BRAIN & DEVELOPMENT, 39(10) (10), 869 - 872, English

  [Refereed]

  Scientific journal


• Deep-intronic variant of fukutin is the most prevalent point mutation of Fukuyama congenital muscular dystrophy in Japan

  Kazuhiro Kobayashi, Reiko Kato, Eri Kondo-Iida, Mariko Taniguchi-Ikeda, Makiko Osawa, Kayoko Saito, Tatsushi Toda

  Nov. 2017, JOURNAL OF HUMAN GENETICS, 62(11) (11), 945 - 948, English

  [Refereed]

  Scientific journal


• The Muscular Dystrophy Gene TMEM5 Encodes a Ribitol beta 1,4-Xylosyltransferase Required for the Functional Glycosylation of Dystroglycan

  Hiroshi Manya, Yoshiki Yamaguchi, Motoi Kanagawa, Kazuhiro Kobayashi, Michiko Tajiri, Keiko Akasaka-Manya, Hiroko Kawakami, Mamoru Mizuno, Yoshinao Wada, Tatsushi Toda, Tamao Endo

  Nov. 2016, JOURNAL OF BIOLOGICAL CHEMISTRY, 291(47) (47), 24618 - 24627, English

  [Refereed]

  Scientific journal


• Carbohydrate-binding domain of the POMGnT1 stem region modulates O-mannosylation sites of alpha-dystroglycan

  Naoyuki Kuwabara, Hiroshi Manya, Takeyuki Yamada, Hiroaki Tateno, Motoi Kanagawa, Kazuhiro Kobayashi, Keiko Akasaka-Manya, Yuriko Hirose, Mamoru Mizuno, Mitsunori Ikeguchi, Tatsushi Toda, Jun Hirabayashi, Toshiya Senda, Tamao Endo, Ryuichi Kato

  Aug. 2016, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 113(33) (33), 9280 - 9285, English

  [Refereed]

  Scientific journal


• Analysis of phenotype, enzyme activity and genotype of Chinese patients with POMT1 mutation

  Haipo Yang, Hiroshi Manya, Kazuhiro Kobayashi, Hui Jiao, Xiaona Fu, Jiangxi Xiao, Xiaoqing Li, Jingmin Wang, Yuwu Jiang, Tatsushi Toda, Tamao Endo, Xiru Wu, Hui Xiong

  Aug. 2016, JOURNAL OF HUMAN GENETICS, 61(8) (8), 753 - 759, English

  [Refereed]

  Scientific journal


• Identification of a Post-translational Modification with Ribitol-Phosphate and Its Defect in Muscular Dystrophy

  Motoi Kanagawa, Kazuhiro Kobayashi, Michiko Tajiri, Hiroshi Manya, Atsushi Kuga, Yoshiki Yamaguchi, Keiko Akasaka-Manya, Jun-ichi Furukawa, Mamoru Mizuno, Hiroko Kawakami, Yasuro Shinohara, Yoshinao Wada, Tamao Endo, Tatsushi Toda

  Mar. 2016, CELL REPORTS, 14(9) (9), 2209 - 2223, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Founder mutation causes classical Fukuyama congenital muscular dystrophy (FCMD) in Chinese patients

  Haipo Yang, Kazuhiro Kobayashi, Shuo Wang, Hui Jiao, Jiangxi Xiao, Tatsushi Toda, Xiru Wu, Hui Xiong

  Oct. 2015, BRAIN & DEVELOPMENT, 37(9) (9), 880 - 886, English

  [Refereed]

  Scientific journal


• Distinct cardiac phenotype between two homozygotes born in a village with accumulation of a genetic deficiency of adipose triglyceride lipase

  Masahiro Higashi, Ken-ichi Hirano, Kazuhiro Kobayashi, Yoshihiko Ikeda, Ami Issiki, Tetsuo Otsuka, Akira Suzuki, Satoshi Yamaguchi, Nobuhiro Zaima, Seiki Hamada, Hironori Hanada, Chieko Suzuki, Hiroshi Nakamura, Hironori Nagasaka, Toshiyuki Miyata, Yoshihiro Miyamoto, Kunihisa Kobayashi, Hiroaki Naito, Tatsushi Toda

  Aug. 2015, INTERNATIONAL JOURNAL OF CARDIOLOGY, 192, 30 - 32, English

  [Refereed]

  Scientific journal


• Fukutin is prerequisite to ameliorate muscular dystrophic phenotype by myofiber-selective LARGE expression

  Yoshihisa Ohtsuka, Motoi Kanagawa, Chih-Chieh Yu, Chiyomi Ito, Tomoko Chiyo, Kazuhiro Kobayashi, Takashi Okada, Shin'ichi Takeda, Tatsushi Toda

  Feb. 2015, SCIENTIFIC REPORTS, 5, 8316, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• A de novo mutation of the MYH7 gene in a large Chinese family with autosomal dominant myopathy.

  Tetsuya Oda, Hui Xiong, Kazuhiro Kobayashi, Shuo Wang, Wataru Satake, Hui Jiao, Yanling Yang, Pei-Chieng Cha, Yukiko K Hayashi, Ichizo Nishino, Yutaka Suzuki, Sumio Sugano, Xiru Wu, Tatsushi Toda

  Laing distal myopathy (LDM) is an autosomal dominant myopathy that is caused by mutations in the slow/beta cardiac myosin heavy-chain (MYH7) gene. It has been recently reported that LDM presents with a wide range of clinical manifestations. We herein report a large Chinese family with autosomal dominant myopathy. The affected individuals in the family presented with foot drop in early childhood, along with progressive distal and proximal limb weakness. Their characteristic symptoms include scapular winging and scoliosis in the early disease phase and impairment of ambulation in the advanced phase. Although limb-girdle muscle dystrophy (LGMD) was suspected initially, a definite diagnosis could not be reached. As such, we performed linkage analysis and detected four linkage regions, namely 1q23.2-24.1, 14q11.2-12, 15q26.2-26.3 and 17q24.3. Through subsequent whole exome sequencing, we found a de novo p.K1617del causative mutation in the MYH7 gene and diagnosed the disease as LDM. This is the first LDM case in China. Our patients have severe clinical manifestations that mimic LGMD in comparison with the patients with the same mutation reported elsewhere.

  2015, Human genome variation, 2, 15022 - 15022, English, International magazine

  [Refereed]

  Scientific journal


• Peripheral leukocyte anomaly detected with routine automated hematology analyzer sensitive to adipose triglyceride lipase deficiency manifesting neutral lipid storage disease with myopathy/triglyceride deposit cardiomyovasculopathy

  Akira Suzuki, Hironori Nagasaka, Yasuhiro Ochi, Kazuhiro Kobayashi, Hiroshi Nakamura, Daisaku Nakatani, Satoshi Yamaguchi, Shinobu Yamaki, Atsushi Wada, Yoshihisa Shirata, Shu-Ping Hui, Tatsushi Toda, Hiroshi Kuroda, Hitoshi Chiba, Ken-Ichi Hirano

  Elsevier Inc., 2014, Molecular Genetics and Metabolism Reports, 1(1) (1), 249 - 253, English

  [Refereed]

  Scientific journal


• Disease-associated marked hyperalphalipoproteinemia

  Ken-Ichi Hirano, Hironori Nagasaka, Kazuhiro Kobayashi, Satoshi Yamaguchi, Akira Suzuki, Tatsushi Toda, Manabu Doyu

  Elsevier Inc., 2014, Molecular Genetics and Metabolism Reports, 1(1) (1), 264 - 268, English

  [Refereed]

  Scientific journal


• Genetic mutations in adipose triglyceride lipase and myocardial up-regulation of peroxisome proliferated activated receptor-gamma in patients with triglyceride deposit cardiomyovasculopathy

  Ken-ichi Hirano, Tatsuya Tanaka, Yoshihiko Ikeda, Satoshi Yamaguchi, Nobuhiro Zaima, Kazuhiro Kobayashi, Akira Suzuki, Yasuhiko Sakata, Yasushi Sakata, Kunihisa Kobayashi, Tatsushi Toda, Norihide Fukushima, Hatsue Ishibashi-Ueda, Daniela Tavian, Hironori Nagasaka, Shu-Ping Hui, Hitoshi Chiba, Yoshiki Sawa, Masatsugu Hori

  Jan. 2014, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 443(2) (2), 574 - 579, English

  [Refereed]

  Scientific journal


• YY1 binds to α-synuclein 3′-flanking region SNP and stimulates antisense noncoding RNA expression

  Ikuko Mizuta, Kazuaki Takafuji, Yuko Ando, Wataru Satake, Motoi Kanagawa, Kazuhiro Kobayashi, Shushi Nagamori, Takayuki Shinohara, Chiyomi Ito, Mitsutoshi Yamamoto, Nobutaka Hattori, Miho Murata, Yoshikatsu Kanai, Shigeo Murayama, Masanori Nakagawa, Tatsushi Toda

  Nov. 2013, Journal of Human Genetics, 58(11) (11), 711 - 719, English

  [Refereed]

  Scientific journal


• Novel POMGnT1 mutations cause muscle-eye-brain disease in Chinese patients

  Hui Jiao, Hiroshi Manya, Shuo Wang, Yanzhi Zhang, Xiaoqing Li, Jiangxi Xiao, Yanling Yang, Kazuhiro Kobayashi, Tatsushi Toda, Tamao Endo, Xiru Wu, Hui Xiong

  Aug. 2013, MOLECULAR GENETICS AND GENOMICS, 288(7-8) (7-8), 297 - 308, English

  [Refereed]

  Scientific journal


• Impaired viability of muscle precursor cells in muscular dystrophy with glycosylation defects and amelioration of its severe phenotype by limited gene expression

  Motoi Kanagawa, Chih-Chieh Yu, Chiyomi Ito, So-ichiro Fukada, Masako Hozoji-Inada, Tomoko Chiyo, Atsushi Kuga, Megumi Matsuo, Kanoko Sato, Masahiko Yamaguchi, Takahito Ito, Yoshihisa Ohtsuka, Yuki Katanosaka, Yuko Miyagoe-Suzuki, Keiji Naruse, Kazuhiro Kobayashi, Takashi Okada, Shin'ichi Takeda, Tatsushi Toda

  Aug. 2013, HUMAN MOLECULAR GENETICS, 22(15) (15), 3003 - 3015, English

  [Refereed]

  Scientific journal


• A novel mutation in the C2 domain of protein kinase C gamma associated with spinocerebellar ataxia type 14.

  Takehiro Ueda, Tsuneyoshi Seki, Kimitaka Katanazaka, Kenji Sekiguchi, Kazuhiro Kobayashi, Fumio Kanda, Tatsushi Toda

  Jun. 2013, Journal of neurology, 260(6) (6), 1664 - 6, English, International magazine

  [Refereed]

  Scientific journal


• [Fukuyama muscular dystrophy: elucidation of the gene and pathogenesis and approaches toward molecular targeting therapy].

  Toda T, Taniguchi-Ikeda M, Kanagawa M, Kobayashi K

  Apr. 2013, Seikagaku. The Journal of Japanese Biochemical Society, 85(4) (4), 253 - 260

  [Refereed]


• Modeling Alzheimer's Disease with iPSCs Reveals Stress Phenotypes Associated with Intracellular A beta and Differential Drug Responsiveness

  Takayuki Kondo, Masashi Asai, Kayoko Tsukita, Yumiko Kutoku, Yutaka Ohsawa, Yoshihide Sunada, Keiko Imamura, Naohiro Egawa, Naoki Yahata, Keisuke Okita, Kazutoshi Takahashi, Isao Asaka, Takashi Aoi, Akira Watanabe, Kaori Watanabe, Chie Kadoya, Rie Nakano, Dai Watanabe, Kei Maruyama, Osamu Hori, Satoshi Hibino, Tominari Choshi, Tatsutoshi Nakahata, Hiroyuki Hioki, Takeshi Kaneko, Motoko Naitoh, Katsuhiro Yoshikawa, Satoko Yamawaki, Shigehiko Suzuki, Ryuji Hata, Shu-ichi Ueno, Tsuneyoshi Seki, Kazuhiro Kobayashi, Tatsushi Toda, Kazuma Murakami, Kazuhiro Irie, William L. Klein, Hiroshi Mori, Takashi Asada, Ryosuke Takahashi, Nobuhisa Iwata, Shinya Yamanaka, Haruhisa Inoue

  Apr. 2013, CELL STEM CELL, 12(4) (4), 487 - 496, English

  [Refereed]

  Scientific journal


• Two Cohort and Three Independent Anonymous Twin Projects at the Keio Twin Research Center (KoTReC)

  Ando, Juko, Fujisawa, Keiko K., Shikishima, Chizuru, Hiraishi, Kai, Nozaki, Mari, Yamagata, Shinji, Takahashi, Yusuke, Ozaki, Koken, Suzuki, Kunitake, Deno, Minako, Sasaki, Shoko, Toda, Tatsushi, Kobayashi, Kazuhiro, Sugimoto, Yutaro, Okada, Mitsuhiro, Kijima, Nobuhiko, Ono, Yutaka, Yoshimura, Kimio, Kakihana, Shinichiro, Maekawa, Hiroko, Kamakura, Toshimitsu, Nonaka, Koichi, Kato, Noriko, Ooki, Syuichi

  Feb. 2013, TWIN RESEARCH AND HUMAN GENETICS, 16(1) (1), 202 - 216, English

  [Refereed]

  Scientific journal


• Genome-Wide DNA Methylation and Gene Expression Analyses of Monozygotic Twins Discordant for Intelligence Levels

  Chih-Chieh Yu, Mari Furukawa, Kazuhiro Kobayashi, Chizuru Shikishima, Pei-Chieng Cha, Jun Sese, Hiroko Sugawara, Kazuya Iwamoto, Tadafumi Kato, Juko Ando, Tatsushi Toda

  Oct. 2012, PLOS ONE, 7(10) (10), English

  [Refereed]

  Scientific journal


• Detection of the dystroglycanopathy protein, fukutin, using a new panel of site-specific monoclonal antibodies

  Tracy A. Lynch, Le Thanh Lam, Nguyen thi Man, Kazuhiro Kobayashi, Tatsushi Toda, Glenn E. Morris

  Jul. 2012, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 424(2) (2), 354 - 357, English

  [Refereed]

  Scientific journal


• Mislocalization of Fukutin Protein by Disease-causing Missense Mutations Can Be Rescued with Treatments Directed at Folding Amelioration

  Masaji Tachikawa, Motoi Kanagawa, Chih-Chieh Yu, Kazuhiro Kobayashi, Tatsushi Toda

  Mar. 2012, JOURNAL OF BIOLOGICAL CHEMISTRY, 287(11) (11), 8398 - 8406, English

  [Refereed]

  Scientific journal


• Absence of Post-phosphoryl Modification in Dystroglycanopathy Mouse Models and Wild-type Tissues Expressing Non-laminin Binding Form of alpha-Dystroglycan

  Atsushi Kuga, Motoi Kanagawa, Atsushi Sudo, Yiumo Michael Chan, Michiko Tajiri, Hiroshi Manya, Yamato Kikkawa, Motoyoshi Nomizu, Kazuhiro Kobayashi, Tamao Endo, Qi L. Lu, Yoshinao Wada, Tatsushi Toda

  Mar. 2012, JOURNAL OF BIOLOGICAL CHEMISTRY, 287(12) (12), 9560 - 9567, English

  [Refereed]

  Scientific journal


• [Molecular targeting therapy for Fukuyama muscular dystrophy].

  Toda T, Taniguchi-Ikeda M, Kobayashi K

  2012, Rinsho shinkeigaku = Clinical neurology, 52(11) (11), 1158

  [Refereed]


• Pathogenic exon-trapping by SVA retrotransposon and rescue in Fukuyama muscular dystrophy

  Mariko Taniguchi-Ikeda, Kazuhiro Kobayashi, Motoi Kanagawa, Chih-chieh Yu, Kouhei Mori, Tetsuya Oda, Atsushi Kuga, Hiroki Kurahashi, Hasan O. Akman, Salvatore DiMauro, Ryuji Kaji, Toshifumi Yokota, Shin'ichi Takeda, Tatsushi Toda

  Oct. 2011, NATURE, 478(7367) (7367), 127 - U143, English

  [Refereed]

  Scientific journal


• The Dyslexia-associated KIAA0319 Protein Undergoes Proteolytic Processing with gamma-Secretase-independent Intramembrane Cleavage

  Antonio Velayos-Baeza, Clotilde Levecque, Kazuhiro Kobayashi, Zoe G. Holloway, Anthony P. Monaco

  Dec. 2010, JOURNAL OF BIOLOGICAL CHEMISTRY, 285(51) (51), 40148 - 40162, English

  Scientific journal


• Post-translational Maturation of Dystroglycan Is Necessary for Pikachurin Binding and Ribbon Synaptic Localization

  Motoi Kanagawa, Yoshihiro Omori, Shigeru Sato, Kazuhiro Kobayashi, Yuko Miyagoe-Suzuki, Shin'ichi Takeda, Tamao Endo, Takahisa Furukawa, Tatsushi Toda

  Oct. 2010, JOURNAL OF BIOLOGICAL CHEMISTRY, 285(41) (41), 31208 - 31216, English

  Scientific journal


• Spinocerebellar Ataxia Type 31 Is Associated with "Inserted" Penta-Nucleotide Repeats Containing (TGGAA)(n)

  Nozomu Sato, Takeshi Amino, Kazuhiro Kobayashi, Shuichi Asakawa, Taro Ishiguro, Taiji Tsunemi, Makoto Takahashi, Tohru Matsuura, Kevin M. Flanigan, Sawa Iwasaki, Fumitoshi Ishino, Yuko Saito, Shigeo Murayama, Mari Yoshida, Yoshio Hashizume, Yuji Takahashi, Shoji Tsuji, Nobuyoshi Shimizu, Tatsushi Toda, Kinya Ishikawa, Hidehiro Mizusawa

  Nov. 2009, AMERICAN JOURNAL OF HUMAN GENETICS, 85(5) (5), 544 - 557, English

  [Refereed]

  Scientific journal


• Fukutin Gene Retrotransposal Insertion in a Non-Japanese Fukuyama Congenital Muscular Dystrophy (FCMD) Patient

  Hui Xiong, Shuo Wang, Kazuhiro Kobayashi, Yuwu Jiang, Jingmin Wang, Xingzhi Chang, Yun Yuan, Jieyu Liu, Tatsushi Toda, Yukio Fukuyama, Xiru Wu

  Nov. 2009, AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 149A(11) (11), 2403 - 2408, English

  [Refereed]

  Scientific journal


• MET and autism susceptibility: family and case-control studies

  Ines Sousa, Taane G. Clark, Claudio Toma, Kazuhiro Kobayashi, Maja Choma, Richard Holt, Nuala H. Sykes, Janine A. Lamb, Anthony J. Bailey, Agatino Battaglia, Elena Maestrini, Anthony P. Monaco

  Jun. 2009, EUROPEAN JOURNAL OF HUMAN GENETICS, 17(6) (6), 749 - 758, English

  [Refereed]

  Scientific journal


• Residual laminin-binding activity and enhanced dystroglycan glycosylation by LARGE in novel model mice to dystroglycanopathy

  Motoi Kanagawa, Akemi Nishimoto, Tomohiro Chiyonobu, Satoshi Takeda, Yuko Miyagoe-Suzuki, Fan Wang, Nobuhiro Fujikake, Mariko Taniguchi, Zhongpeng Lu, Masaji Tachikawa, Yoshitaka Nagai, Fumi Tashiro, Jun-Ichi Miyazaki, Youichi Tajima, Shin'ichi Takeda, Tamao Endo, Kazuhiro Kobayashi, Kevin P. Campbell, Tatsushi Toda

  Feb. 2009, HUMAN MOLECULAR GENETICS, 18(4) (4), 621 - 631, English

  [Refereed]

  Scientific journal


• Reduced expression of sarcospan in muscles of Fukuyama congenital muscular dystrophy

  Yoshihiro Wakayama, Masahiko Inoue, Hiroko Kojima, Sumimasa Yamashita, Seiji Shibuya, Takahiro Jimi, Hajime Hara, Yoko Matsuzaki, Hiroaki Oniki, Motoi Kanagawa, Kazuhiro Kobayashi, Tatsushi Toda

  Dec. 2008, HISTOLOGY AND HISTOPATHOLOGY, 23(12) (12), 1425 - 1438, English

  Scientific journal


• Pikachurin, a dystroglycan ligand, is essential for photoreceptor ribbon synapse formation

  Shigeru Sato, Yoshihiro Omori, Kimiko Katoh, Mineo Kondo, Motoi Kanagawa, Kentaro Miyata, Kazuo Funabiki, Toshiyuki Koyasu, Naoko Kajimura, Tomomitsu Miyoshi, Hajime Sawai, Kazuhiro Kobayashi, Akiko Tani, Tatsushi Toda, Jiro Usukura, Yasuo Tano, Takashi Fujikado, Takahisa Furukawa

  Aug. 2008, NATURE NEUROSCIENCE, 11(8) (8), 923 - 931, English

  [Refereed]

  Scientific journal


• Redefining the disease locus of 16q22.1-linked autosomal dominant cerebellar ataxia

  Takeshi Amino, Kinya Ishikawa, Shuta Toru, Taro Ishiguro, Nozomu Sato, Taiji Tsunemi, Miho Murata, Kazuhiro Kobayashi, Johji Inazawa, Tatsushi Toda, Hidehiro Mizusawa

  Aug. 2007, JOURNAL OF HUMAN GENETICS, 52(8) (8), 643 - 649, English

  [Refereed]

  Scientific journal


• Partial tandem duplication of GRIA3 in a male with mental retardation

  Tomohiro Chiyonobu, Shin Hayashi, Kazuhiro Kobayashi, Masafumi Morimoto, Yuri Miyanomae, Akira Nishimura, Akemi Nishimoto, Chiyomi Ito, Issei Imoto, Tohru Sugimoto, Zhengping Jia, Johji Inazawa, Tatsushi Toda

  Jul. 2007, AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 143A(13) (13), 1448 - 1455, English

  [Refereed]

  Scientific journal


• Mapping autism risk loci using genetic linkage and chromosomal rearrangements

  Peter Szatmari, Andrew D. Paterson, Lonnie Zwaigenbaum, Wendy Roberts, Jessica Brian, Xiao-Qing Liu, John B. Vincent, Jennifer L. Skaug, Ann P. Thompson, Lili Senman, Lars Feuk, Cheng Qian, Susan E. Bryson, Marshall B. Jones, Christian R. Marshall, Stephen W. Scherer, Veronica J. Vieland, Christopher Bartlett, La Vonne Mangin, Rhinda Goedken, Alberto Segre, Margaret A. Pericak-Vance, Michael L. Cuccaro, John R. Gilbert, Harry H. Wright, Ruth K. Abramson, Catalina Betancur, Thomas Bourgeron, Christopher Gillberg, Marion Leboyer, Joseph D. Buxbaum, Kenneth L. Davis, Eric Hollander, Jeremy M. Silverman, Joachim Hallmayer, Linda Lotspeich, James S. Sutcliffe, Jonathan L. Haines, Susan E. Folstein, Joseph Piven, Thomas H. Wassink, Val Sheffield, Daniel H. Geschwind, Maja Bucan, W. Ted Brown, Rita M. Cantor, John N. Constantino, T. Conrad Gilliam, Martha Herbert, Clara LaJonchere, David H. Ledbetter, Christa Lese-Martin, Janet Miller, Stan Nelson, Carol A. Samango-Sprouse, Sarah Spence, Matthew State, Rudolph E. Tanzi, Hilary Coon, Geraldine Dawson, Bernie Devlin, Annette Estes, Pamela Flodman, Lambertus Klei, William M. McMahon, Nancy Minshew, Jeff Munson, Elena Korvatska, Patricia M. Rodier, Gerard D. Schellenberg, Moyra Smith, M. Anne Spence, Chris Stodgell, Ping Guo Tepper, Ellen M. Wijsman, Chang-En Yu, Bernadette Roge, Carine Mantoulan, Kerstin Wittemeyer, Annemarie Poustka, Barbel Felder, Sabine M. Klauck, Claudia Schuster, Fritz Poustka, Sven Boelte, Sabine Feineis-Matthews, Evelyn Herbrecht, Gabi Schmoetzer, John Tsiantis, Katerina Papanikolaou, Elena Maestrini, Elena Bacchelli, Francesca Blasi, Simona Carone, Claudio Toma, Herman Van Engeland, Maretha de Jonge, Chantal Kemner, Frederike Koop, Marjolijn Langemeijer, Channa Hijimans, Wouter G. Staal, Gillian Baird, Patrick F. Bolton, Michael L. Rutter, Emma Weisblatt, Jonathan Green, Catherine Aldred, Julie-Anne Wilkinson, Andrew Pickles, Ann Le Couteur, Tom Berney, Helen McConachie, Anthony J. Bailey, Kostas Francis, Gemma Honeyman, Aislinn Hutchinson, Jeremy R. Parr, Simon Wallace, Anthony P. Monaco, Gabrielle Barnby, Kazuhiro Kobayashi, Janine A. Lamb, Ines Sousa, Nuala Sykes, Edwin H. Cook, Stephen J. Guter, Bennett L. Leventhal, Jeff Salt, Catherine Lord, Christina Corsello, Vanessa Hus, Daniel E. Weeks, Fred Volkmar, Maite Tauber, Eric Fombonne, Andy Shih

  Mar. 2007, NATURE GENETICS, 39(3) (3), 319 - 328, English

  [Refereed]

  Scientific journal


• Mapping autism risk loci using genetic linkage and chromosomal rearrangements

  Peter Szatmari, Andrew D. Paterson, Lonnie Zwaigenbaum, Wendy Roberts, Jessica Brian, Xiao-Qing Liu, John B. Vincent, Jennifer L. Skaug, Ann P. Thompson, Lili Senman, Lars Feuk, Cheng Qian, Susan E. Bryson, Marshall B. Jones, Christian R. Marshall, Stephen W. Scherer, Veronica J. Vieland, Christopher Bartlett, La Vonne Mangin, Rhinda Goedken, Alberto Segre, Margaret A. Pericak-Vance, Michael L. Cuccaro, John R. Gilbert, Harry H. Wright, Ruth K. Abramson, Catalina Betancur, Thomas Bourgeron, Christopher Gillberg, Marion Leboyer, Joseph D. Buxbaum, Kenneth L. Davis, Eric Hollander, Jeremy M. Silverman, Joachim Hallmayer, Linda Lotspeich, James S. Sutcliffe, Jonathan L. Haines, Susan E. Folstein, Joseph Piven, Thomas H. Wassink, Val Sheffield, Daniel H. Geschwind, Maja Bucan, W. Ted Brown, Rita M. Cantor, John N. Constantino, T. Conrad Gilliam, Martha Herbert, Clara LaJonchere, David H. Ledbetter, Christa Lese-Martin, Janet Miller, Stan Nelson, Carol A. Samango-Sprouse, Sarah Spence, Matthew State, Rudolph E. Tanzi, Hilary Coon, Geraldine Dawson, Bernie Devlin, Annette Estes, Pamela Flodman, Lambertus Klei, William M. McMahon, Nancy Minshew, Jeff Munson, Elena Korvatska, Patricia M. Rodier, Gerard D. Schellenberg, Moyra Smith, M. Anne Spence, Chris Stodgell, Ping Guo Tepper, Ellen M. Wijsman, Chang-En Yu, Bernadette Roge, Carine Mantoulan, Kerstin Wittemeyer, Annemarie Poustka, Barbel Felder, Sabine M. Klauck, Claudia Schuster, Fritz Poustka, Sven Boelte, Sabine Feineis-Matthews, Evelyn Herbrecht, Gabi Schmoetzer, John Tsiantis, Katerina Papanikolaou, Elena Maestrini, Elena Bacchelli, Francesca Blasi, Simona Carone, Claudio Toma, Herman Van Engeland, Maretha de Jonge, Chantal Kemner, Frederike Koop, Marjolijn Langemeijer, Channa Hijimans, Wouter G. Staal, Gillian Baird, Patrick F. Bolton, Michael L. Rutter, Emma Weisblatt, Jonathan Green, Catherine Aldred, Julie-Anne Wilkinson, Andrew Pickles, Ann Le Couteur, Tom Berney, Helen McConachie, Anthony J. Bailey, Kostas Francis, Gemma Honeyman, Aislinn Hutchinson, Jeremy R. Parr, Simon Wallace, Anthony P. Monaco, Gabrielle Barnby, Kazuhiro Kobayashi, Janine A. Lamb, Ines Sousa, Nuala Sykes, Edwin H. Cook, Stephen J. Guter, Bennett L. Leventhal, Jeff Salt, Catherine Lord, Christina Corsello, Vanessa Hus, Daniel E. Weeks, Fred Volkmar, Maite Tauber, Eric Fombonne, Andy Shih

  Mar. 2007, NATURE GENETICS, 39(3) (3), 319 - 328, English

  [Refereed]

  Scientific journal


• Molecular interaction between fukutin and POMGnT1 in the glycosylation pathway of alpha-dystroglycan

  Hui Xiong, Kazuhiro Kobayashi, Masaji Tachikawa, Hiroshi Manya, Satoshi Takeda, Tomohiro Chiyonobu, Nobuhiro Fujikake, Fan Wang, Akemi Nishimoto, Glenn E. Morris, Yoshitaka Nagai, Motoi Kanagawa, Tarnao Endo, Tatsushi Toda

  Dec. 2006, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 350(4) (4), 935 - 941, English

  [Refereed]

  Scientific journal


• Founder SVA retrotransposal insertion in Fukuyama-type congenital muscular dystrophy and its origin in Japanese and northeast Asian populations

  M Watanabe, K Kobayashi, F Jin, KS Park, T Yamada, K Tokunaga, T Toda

  Nov. 2005, AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 138A(4) (4), 344 - 348, English

  [Refereed]

  Scientific journal


• Fukutin and α-dystroglycanopahties

  Tatsushi Toda, T. Chiyonobu, H. Xiong, M. Tachikawa, K. Kobayashi, H. Manya, S. Takeda, M. Taniguchi, H. Kurahashi, T. Endo

  Oct. 2005, Acta Myologica, 24(2) (2), 60 - 63, English

  [Refereed]

  International conference proceedings


• An autosomal dominant cerebellar ataxia linked to chromosome 16q22.1 is associated with a single-nucleotide substitution in the 5 '-untranslated region of the gene encoding a protein with spectrin repeat and Rho guanine-nucleotide exchange-factor domains

  K Ishikawa, S Toru, T Tsunemi, MS Li, K Kobayashi, T Yokota, T Amino, K Owada, H Fujigasaki, M Sakamoto, H Tomimitsu, M Takashima, J Kumagai, Y Noguchi, Y Kawashima, N Ohkoshi, G Ishida, M Gomyoda, M Yoshida, Y Hashizume, Y Saito, S Murayama, H Yamanouchi, T Mizutani, Kondo, I, T Toda, H Mizusawa

  Aug. 2005, AMERICAN JOURNAL OF HUMAN GENETICS, 77(2) (2), 280 - 296, English

  [Refereed]

  Scientific journal


• beta 4GalT-II is a key regulator of glycosylation of the proteins involved in neuronal development

  N Sasaki, H Manya, R Okubo, K Kobayashi, H Ishida, T Toda, T Endo, S Nishihara

  Jul. 2005, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 333(1) (1), 131 - 137, English

  [Refereed]

  Scientific journal


• beta 4GalT-II is a key regulator of glycosylation of the proteins involved in neuronal development

  N Sasaki, H Manya, R Okubo, K Kobayashi, H Ishida, T Toda, T Endo, S Nishihara

  Jul. 2005, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 333(1) (1), 131 - 137, English

  [Refereed]

  Scientific journal


• Structure-function analysis of human protein O-linked mannose beta 1,2-N-acetylglucosaminyltransferase 1, POMGnT1

  K Akasaka-Manya, H Manya, K Kobayashi, T Toda, T Endo

  Jul. 2004, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 320(1) (1), 39 - 44, English

  [Refereed]

  Scientific journal


• Worldwide distribution and broader clinical spectrum of muscle-eye-brain disease

  Toda T, Taniguchi K, Kobayashi K, Saito K, Yamanouchi H, Ohnuma A, Hayashi YK, Jin DK, Parano E, van Coster R, Steinbrecher A, Straub V, Nishino I, Topaloglu H, Voit T, Endo T

  Sep. 2003, NEUROMUSCULAR DISORDERS, 13(7-8) (7-8), 636

  [Refereed]


• Loss-of-function of an N-acetylglucosaminyltransferase, POMGnT1, in muscle-eye-brain disease

  H Manya, K Sakai, K Kobayashi, K Taniguchi, M Kawakita, T Toda, T Endo

  Jun. 2003, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 306(1) (1), 93 - 97, English

  [Refereed]

  Scientific journal


• Fukutin is required for maintenance of muscle integrity, cortical histiogenesis and normal eye development

  S Takeda, M Kondo, J Sasaki, H Kurahashi, H Kano, K Arai, K Misaki, T Fukui, K Kobayashi, M Tachikawa, M Imamura, Y Nakamura, T Shimizu, T Murakami, Y Sunada, T Fujikado, K Matsumura, T Terashima, T Toda

  Jun. 2003, HUMAN MOLECULAR GENETICS, 12(12) (12), 1449 - 1459, English

  [Refereed]

  Scientific journal


• Worldwide distribution and broader clinical spectrum of muscle-eye-brain disease

  K Taniguchi, K Kobayashi, K Saito, H Yamanouchi, A Ohnuma, YK Hayashi, H Manya, DK Jin, M Lee, E Parano, R Falsaperla, P Pavone, R Van Coster, B Talim, A Steinbrecher, Straub, V, Nishino, I, H Topaloglu, T Voit, T Endo, T Toda

  Mar. 2003, HUMAN MOLECULAR GENETICS, 12(5) (5), 527 - 534, English

  [Refereed]

  Scientific journal


• A new mutation of the fukutin gene in a non-Japanese patient

  F Silan, M Yoshioka, K Kobayashi, E Simsek, M Tunc, M Alper, M Cam, A Guven, Y Fukuda, M Kinoshita, K Kocabay, T Toda

  Mar. 2003, ANNALS OF NEUROLOGY, 53(3) (3), 392 - 396, English

  [Refereed]

  Scientific journal


• Fukuyama-type congenital muscular dystrophy and abnormal glycosylation of alpha-dystroglycan.

  Toda Tatsushi, Kobayashi Kazuhiro, Takeda S, Sasaki J, Kurahashi H, Kano H, Tachikawa M, Wang F, Nagai Y, Taniguchi K, Taniguchi M, Sunada Y, Terashima T, Endo T, Matsumura K

  2003, Basic and Applied Myology, 13, 287 - 292, English

  [Refereed]

  Scientific journal


• Isolation and characterization of the mouse ortholog of the fukuyama-type congenital muscular dystrophy gene

  M Horie, K Kobayashi, S Takeda, Y Nakamura, GE Lyons, T Toda

  Nov. 2002, GENOMICS, 80(5) (5), 482 - 486, English

  [Refereed]

  Scientific journal


• Isolation and characterization of the mouse ortholog of the fukuyama-type congenital muscular dystrophy gene

  M Horie, K Kobayashi, S Takeda, Y Nakamura, GE Lyons, T Toda

  Nov. 2002, GENOMICS, 80(5) (5), 482 - 486, English

  [Refereed]

  Scientific journal


• Deficiency of alpha-dystroglycan in muscle-eye-brain disease

  H Kano, K Kobayashi, R Herrmann, M Tachikawa, H Manya, Nishino, I, Nonaka, I, Straub, V, B Talim, T Voit, H Topaloglu, T Endo, H Yoshikawa, T Toda

  Mar. 2002, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 291(5) (5), 1283 - 1286, English

  [Refereed]

  Scientific journal


• Erratum: Deficiency of α-dystroglycan in muscle-eye-brain disease (Biochemical and Biophysical Research Communications (2002) 291 (1283-1286) PII: S0006291X02966088)

  Hiroki Kano, Kazuhiro Kobayashi, Ralf Herrmann, Masaji Tachikawa, Hiroshi Manya, Ichizo Nishino, Ikuya Nonaka, Volker Straub, Beril Talim, Thomas Voit, Haluk Topaloglu, Tamao Endo, Hideki Yoshikawa

  2002, Biochemical and Biophysical Research Communications, 293(5) (5), 1579, English

  [Refereed]

  Scientific journal


• Identification of CAG repeat-containing genes expressed in human brain as candidate genes for autosomal dominant spinocerebellar ataxias and other neurodegenerative diseases

  M Tachikawa, Y Nagai, K Nakamura, K Kobayashi, T Fujiwara, HJ Han, Y Nakabayashi, Y Ichikawa, J Goto, Kanazawa, I, Y Nakamura, T Toda

  2002, JOURNAL OF HUMAN GENETICS, 47(6) (6), 275 - 278, English

  [Refereed]

  Scientific journal


• Association studies of multiple candidate genes for Parkinson's disease using single nucleotide polymorphisms

  Y Momose, M Murata, K Kobayashi, M Tachikawa, Y Nakabayashi, Kanazawa, I, T Toda

  Jan. 2002, ANNALS OF NEUROLOGY, 51(1) (1), 133 - 136, English

  [Refereed]

  Scientific journal


• Muscular dystrophy and neuronal migration disorder caused by mutations in a glycosyltransferase, POMGnT1

  A Yoshida, K Kobayashi, H Manya, K Taniguchi, H Kano, M Mizuno, T Inazu, H Mitsuhashi, S Takahashi, M Takeuchi, R Herrmann, Straub, V, B Talim, T Voit, H Tapaloglu, T Toda, T Endo

  Nov. 2001, DEVELOPMENTAL CELL, 1(5) (5), 717 - 724, English

  [Refereed]

  Scientific journal


• Structural organization, complete genomic sequences and mutational analyses of the Fukuyama-type congenital muscular dystrophy gene, fukutin

  K Kobayashi, J Sasaki, E Kondo-Iida, Y Fukuda, M Kinoshita, Y Sunada, Y Nakamura, T Toda

  Feb. 2001, FEBS LETTERS, 489(2-3) (2-3), 192 - 196, English

  [Refereed]

  Scientific journal


• Moecular genetics of Fukutyama CMD and fukutin.

  Toda T, Sasaki J, Tachikawa M, Kano H, Kobayashi Kazuhiro

  2001, Acta Myologica, 20, 92 - 95, English

  [Refereed]

  Scientific journal


• Neuronal expression of the fukutin gene

  J Sasaki, K Ishikawa, K Kobayashi, E Kondo-Iida, M Fukayama, H Mizusawa, S Takashima, Y Sakakihara, Y Nakamura, T Toda

  Dec. 2000, HUMAN MOLECULAR GENETICS, 9(20) (20), 3083 - 3090, English

  [Refereed]

  Scientific journal


• Age and origin of the FCMD 3 '-untranslated-region retrotransposal insertion mutation causing Fukuyama-type congenital muscular dystrophy in the Japanese population

  R Colombo, AA Bignamini, A Carobene, J Sasaki, M Tachikawa, K Kobayashi, T Toda

  Dec. 2000, HUMAN GENETICS, 107(6) (6), 559 - 567, English

  [Refereed]

  Scientific journal


• Walker-Warburg syndrome is genetically distinct from Fukuyama type congenital muscular dystrophy

  Y Chadani, T Kondoh, N Kamimura, T Matsumoto, T Matsuzaka, O Kobayashi, E Kondo-Iida, K Kobayashi, Nonaka, I, T Toda

  Aug. 2000, JOURNAL OF THE NEUROLOGICAL SCIENCES, 177(2) (2), 150 - 153, English

  [Refereed]

  Scientific journal


• The Fukuyama congenital muscular dystrophy story

  T Toda, K Kobayashi, E Kondo-Iida, J Sasaki, Y Nakamura

  Mar. 2000, NEUROMUSCULAR DISORDERS, 10(3) (3), 153 - 159, English

  [Refereed]

  Scientific journal


• Genetic heterogeneity in three Chinese children with Fukuyama congenital muscular dystrophy

  YJ Jong, K Kobayashi, T Toda, E Kondo-lida, SC Huang, YZ Shen, Nonaka, I, Y Fukuyama

  Feb. 2000, NEUROMUSCULAR DISORDERS, 10(2) (2), 108 - 112, English

  [Refereed]

  Scientific journal


• Congenital muscular dystrophies with special reference to the Fukuyama type.

  Toda T, Kobayashi Kazuhiro, Nonaka I

  2000, Neuroscience News, 3, 39 - 45, English

  [Refereed]

  Scientific journal


• Fukuyama-type congenital muscular dystrophy: the first human disease to be caused by an ancient retrotransposal integration

  T Toda, K Kobayashi

  Dec. 1999, JOURNAL OF MOLECULAR MEDICINE-JMM, 77(12) (12), 816 - 823, English

  [Refereed]

  Scientific journal


• Novel mutations and genotype-phenotype relationships in 107 families with Fukuyama-type congenital muscular dystrophy (FCMD)

  E Kondo-Iida, K Kobayashi, M Watanabe, J Sasaki, T Kumagai, H Koide, K Saito, M Osawa, Y Nakamura, T Toda

  Nov. 1999, HUMAN MOLECULAR GENETICS, 8(12) (12), 2303 - 2309, English

  [Refereed]

  Scientific journal


• Founder-haplotype analysis in Fukuyama-type congenital muscular dystrophy (FCMD)

  K Kobayashi, Y Nakahori, K Mizuno, M Miyake, T Kumagai, A Honma, Nonaka, I, Y Nakamura, K Tokunaga, T Toda

  Sep. 1998, HUMAN GENETICS, 103(3) (3), 323 - 327, English

  [Refereed]

  Scientific journal


• An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy

  K Kobayashi, Y Nakahori, M Miyake, K Matsumura, E Kondo-Iida, Y Nomura, M Segawa, M Yoshioka, K Saito, K Osawa, K Hamano, Y Sakakihara, Nonaka, I, Y Nakagome, Kanazawa, I, Y Nakamura, K Tokunaga, T Toda

  Jul. 1998, NATURE, 394(6691) (6691), 388 - 392, English

  [Refereed]

  Scientific journal


• Prenatal diagnosis of Fukuyama-type congenital muscular dystrophy by microsatellite analysis

  Y Takai, O Tsutsumi, Harada, I, T Fujii, T Kashima, K Kobayashi, T Toda, Y Taketani

  Feb. 1998, HUMAN REPRODUCTION, 13(2) (2), 320 - 323, English

  [Refereed]

  Scientific journal


• YAC and cosmid contigs encompassing the Fukuyama-type congenital muscular dystrophy (FCMD) candidate region on 9q31

  M Miyake, Y Nakahori, Matsushita, I, K Kobayashi, K Mizuno, M Hirai, Kanazawa, I, Y Nakagome, K Tokunaga, T Toda

  Mar. 1997, GENOMICS, 40(2) (2), 284 - 293, English

  [Refereed]

  Scientific journal


• Linkage-disequilibrium mapping narrows the fukuyama-type congenital muscular dystrophy (FCMD) candidate region to <100 kb

  T Toda, M Miyake, K Kobayashi, K Mizuno, K Saito, M Osawa, Y Nakamura, Kanazawa, I, Y Nakagome, K Tokunaga, Y Nakahori

  Dec. 1996, AMERICAN JOURNAL OF HUMAN GENETICS, 59(6) (6), 1313 - 1320, English

  [Refereed]

  Scientific journal


• The Y chromosome region essential for spermatogenesis

  Y Nakahori, Y Kuroki, R Komaki, N Kondoh, M Namiki, T Iwamoto, T Toda, K Kobayashi

  1996, HORMONE RESEARCH, 46, 20 - 23, English

  [Refereed]

  Scientific journal


• PCR ANALYSIS OF THE Y-CHROMOSOME LONG ARM IN AZOOSPERMIC PATIENTS - EVIDENCE FOR A 2ND LOCUS REQUIRED FOR SPERMATOGENESIS

  K KOBAYASHI, K MIZUNO, A HIDA, R KOMAKI, K TOMITA, MATSUSHITA, I, M NAMIKI, T IWAMOTO, S TAMURA, S MINOWADA, Y NAKAHORI, Y NAKAGOME

  Nov. 1994, HUMAN MOLECULAR GENETICS, 3(11) (11), 1965 - 1967, English

  [Refereed]

  Scientific journal


• A LOCUS OF THE CANDIDATE GENE FAMILY FOR AZOOSPERMIA FACTOR (YRRM2) IS POLYMORPHIC WITH A NULL ALLELE IN JAPANESE MALES

  Y NAKAHORI, K KOBAYASHI, R KOMAKI, MATSUSHITA, I, Y NAKAGOME

  Sep. 1994, HUMAN MOLECULAR GENETICS, 3(9) (9), 1709 - 1709, English

  [Refereed]

  Scientific journal

• CDP-リビトールプロドラッグ治療はISPD欠損筋ジストロフィーマウスモデルを改善する

  徳岡 秀紀, 今江 理恵子, 中島 瞳, 萬谷 博, 増田 千明, 星野 駿介, 小林 千浩, Lefeber Dirk J., 松本 理器, 岡田 尚巳, 遠藤 玉夫, 金川 基, 戸田 達史

  (一社)日本筋学会, Aug. 2022, 日本筋学会学術集会プログラム・抄録集, 8回, 58 - 58, Japanese


• ジストログリカノパチーモデルマウスの中枢神経病態の解析

  首藤 篤史, 金川 基, 小林 千浩, 戸田 達史

  (一社)日本筋学会, Aug. 2022, 日本筋学会学術集会プログラム・抄録集, 8回, 117 - 117, Japanese


• Galectin 3 binding protein suppresses A beta production by modulating beta-cleavage of amyloid precursor protein

  Tsuneyoshi Seki, Motoi Kanagawa, Kazuhiro Kobayashi, Hisatomo Kowa, Naoki Yahata, Kei Maruyama, Nobuhisa Iwata, Haruhisa Inoue, Tatsushi Toda

  Apr. 2020, NEUROLOGY, 94(15) (15), English

  Summary international conference


• Galectin 3 binding proteinはBACE1活性を制御しAβ産生を抑制する

  関 恒慶, 金川 基, 小林 千浩, 古和 久朋, 八幡 直樹, 丸山 敬, 岩田 修永, 井上 治久, 戸田 達史

  (一社)日本認知症学会, Oct. 2019, Dementia Japan, 33(4) (4), 516 - 516, Japanese

  [Refereed]


• Galectin 3 binding proteinは内在性のβ-セクレターゼ活性を制御することでAβ産生を抑制する

  関 恒慶, 金川 基, 小林 千浩, 古和 久朋, 八幡 直樹, 丸山 敬, 岩田 修永, 井上 治久, 戸田 達史

  (公社)日本生化学会, Sep. 2019, 日本生化学会大会プログラム・講演要旨集, 92回, [2T17m - 02], Japanese

  [Refereed]


• 近接ライゲーションアッセイを用いた多系統萎縮症におけるαシヌクレインオリゴマーの広範な分布

  関谷 博顕, 古和 久朋, 古閑 日奈子, 高田 真利子, 佐竹 渉, 二村 直伸, 舟川 格, 陣内 研二, 金川 基, 小林 千浩, 戸田 達史

  Movement Disorder Society of Japan (MDSJ), Jul. 2019, パーキンソン病・運動障害疾患コングレスプログラム・抄録集, 13回, 104 - 104, Japanese


• ラミニン-511E8領域由来のジストログリカン(DG)結合ペプチドに対するヒトiPS細胞の接着

  吉川 大和, 菅原 由美香, 濱田 圭佑, 山田 雄二, 熊井 準, 金川 基, 小林 千浩, 戸田 達史, 根岸 洋一, 片桐 文彦, 保住 健太郎, 野水 基義

  日本結合組織学会, May 2019, 日本結合組織学会学術大会プログラム・抄録集, 51回, 139 - 139, Japanese


• ラミニン-511E8領域由来のジストログリカン(DG)結合ペプチドに対するヒトiPS細胞の接着

  吉川 大和, 菅原 由美香, 濱田 圭佑, 山田 雄二, 熊井 準, 金川 基, 小林 千浩, 戸田 達史, 根岸 洋一, 片桐 文彦, 保住 健太郎, 野水 基義

  日本結合組織学会, May 2019, 日本結合組織学会学術大会プログラム・抄録集, 51回, 139 - 139, Japanese


• Wide distribution of alph-synuclein oligomers in multiple system atrophy brain detected by proximity ligation

  Hiroaki Sekiya, Hisatomo Kowa, Hinako Koga, Mariko Takata, Wataru Satake, Naonobu Futamura, Itaru Funakawa, Kenji Jinnai, Motonori Takahashi, Takeshi Kondo, Yasuhiro Ueno, Motoi Kanagawa, Kazuhiro Kobayashi, Tatsushi Toda

  Apr. 2019, NEUROLOGY, 92(15) (15), English

  Summary international conference


• ゲノムワイド関連解析(GWAS)データを活用したin silico解析による新規抗パーキンソン病薬の探索

  上中 健, 佐竹 渉, Cha Pei-Chieng, 早川 英規, 馬場 孝輔, 小林 千浩, 金川 基, 岡田 随象, 望月 秀樹, 戸田 達史

  (公社)日本生化学会, Sep. 2018, 日本生化学会大会プログラム・講演要旨集, 91回, [2T13m - 335)], Japanese


• CDP-glycerolはα-ジストログリカンの糖鎖伸長を阻害する

  今江 理恵子, 萬谷 博, 津元 裕樹, 田中 智博, 水野 真盛, 金川 基, 小林 千浩, 戸田 達史, 遠藤 玉夫

  (公社)日本生化学会, Sep. 2018, 日本生化学会大会プログラム・講演要旨集, 91回, [1P - 033], Japanese


• 福山型筋ジストロフィー原因遺伝子産物fukutinのグリセロールリン酸転移活性

  萬谷 博, 今江 理恵子, 津元 裕樹, 田中 智博, 水野 真盛, 金川 基, 小林 千浩, 戸田 達史, 遠藤 玉夫

  日本筋学会, Aug. 2018, 日本筋学会学術集会プログラム・抄録集, 4回, 162 - 162, Japanese


• 筋ジストロフィー症原因遺伝子産物フクチンはジストログリカン糖鎖にグリセロールリン酸を導入する活性を有する

  今江 理恵子, 萬谷 博, 津元 裕樹, 田中 智博, 水野 真盛, 金川 基, 小林 千浩, 戸田 達史, 遠藤 玉夫

  (公社)日本薬学会, Mar. 2018, 日本薬学会年会要旨集, 138年会(3) (3), 105 - 105, Japanese


• 新規糖鎖修飾体グリセロールリン酸によるα-ジストログリカンの機能糖鎖合成阻害

  今江理恵子, 萬谷博, 津元裕樹, 田中智博, 水野真盛, 金川基, 小林千浩, 戸田達史, 遠藤玉夫

  2018, 日本糖質学会年会要旨集, 37th


• 糖鎖修飾と、末梢組織から見た神経系疾患 ジストログリカン異常症の原因となるリビトールリン酸タンデム構造とその生合成経路

  小林 千浩, 戸田 達史

  生命科学系学会合同年次大会運営事務局, Dec. 2017, 生命科学系学会合同年次大会, 2017年度, [1AW27 - 3], Japanese


• POMGnT1の構造解析による筋ジストロフィー疾患発症機序解明

  桑原 直之, 萬谷 博, 山田 健之, 舘野 浩章, 金川 基, 小林 千浩, 赤阪 啓子[萬谷], 弘瀬 友理子, 水野 真盛, 池口 満徳, 戸田 達史, 平林 淳, 千田 俊哉, 遠藤 玉夫, 加藤 龍一

  生命科学系学会合同年次大会運営事務局, Dec. 2017, 生命科学系学会合同年次大会, 2017年度, [1AT26 - 0062)], Japanese


• ゲノムワイド関連解析データを活用したインシリコスクリーニングによる新規抗パーキンソン病薬の同定

  上中 健, 佐竹 渉, Cha Pei-Chieng, 早川 英規, 馬場 孝輔, 小林 千浩, 金川 基, 岡田 随象, 望月 秀樹, 戸田 達史

  生命科学系学会合同年次大会運営事務局, Dec. 2017, 生命科学系学会合同年次大会, 2017年度, [3LBA - 124], English


• ジストログリカノパチーモデルマウスの中枢神経病態の解析

  首藤 篤史, 金川 基, 近藤 舞, 小林 千浩, 遠藤 光晴, 南 康博, 戸田 達史

  生命科学系学会合同年次大会運営事務局, Dec. 2017, 生命科学系学会合同年次大会, 2017年度, [4LT02 - 1095)], Japanese


• α-ジストログリカノパチー原因遺伝子産物TMEM5によるジストログリカン糖鎖の修飾

  萬谷 博, 山口 芳樹, 金川 基, 小林 千浩, 田尻 道子, 赤阪 啓子[萬谷], 川上 宏子, 水野 真盛, 和田 芳直, 戸田 達史, 遠藤 玉夫

  日本筋学会, Jul. 2017, 日本筋学会学術集会プログラム・抄録集, 3回, 98 - 98, Japanese


• ジストログリカノパチーに対するLARGE遺伝子治療

  大塚 喜久, 金川 基, 千代 智子, 小林 千浩, 岡田 尚巳, 武田 伸一, 戸田 達史

  日本筋学会, Jul. 2017, 日本筋学会学術集会プログラム・抄録集, 3回, 142 - 142, Japanese


• Identification of a post-translational modification with ribitol-phosphate and its defect in muscular dystrophy: Roles of ISPD, fukutin, and FKRP in alpha-dystroglycan glycosylation

  Motoi Kanagawa, Kazuhiro Kobayashi, Michiko Tajiri, Hiroshi Manya, Atsushi Kuga, Yoshiki Yamaguchi, Yoshinao Wada, Tamao Endo, Tatsushi Toda

  Apr. 2017, FASEB JOURNAL, 31, English

  Summary international conference


• 筋ジストロフィー症原因遺伝子TMEM5はジストログリカンの機能糖鎖修飾に必要なβ1,4-xylosyltransferaseをコードする

  萬谷 博, 山口 芳樹, 金川 基, 小林 千浩, 田尻 道子, 赤阪 啓子[萬谷], 川上 宏子, 水野 真盛, 和田 芳直, 戸田 達史, 遠藤 玉夫

  (公社)日本薬学会, Mar. 2017, 日本薬学会年会要旨集, 137年会(3) (3), 53 - 53, Japanese


• ドーパミントランスポーターシンチグラフィー(DAT SPECT)で高度集積低下のみられたSPG15の1例

  三谷 真紀, 藤堂 紘行, 福田 明, 西田 勝也, 安藤 竜起, 山崎 浩, 西本 啓介, 河本 邦彦, 二村 直伸, 舟川 格, 宮脇 統子, 小林 千浩, 古和 久朋, 石原 浩之, 辻 省次

  (一社)日本神経学会, Nov. 2016, 臨床神経学, 56(11) (11), 797 - 797, Japanese


• Identification of a post-translational modification with ribitol-phosphate and its defect in muscular dystrophy

  T. Toda, M. Kanagawa, K. Kobayashi, M. Tajiri, H. Manya, A. Kuga, Y. Yamaguchi, Y. Wada, T. Endo

  Oct. 2016, NEUROMUSCULAR DISORDERS, 26, S90 - S90, English

  Summary international conference


• Identification of a Post-Translational Modification with Ribitol-Phosphate and Its Defect in Muscular Dystrophy

  Tatsushi Toda, Motoi Kanagawa, Kazuhiro Kobayashi, Michiko Tajiri, Hiroshi Manya, Atsushi Kuga, Yoshiki Yamaguchi, Yoshinao Wada, Tamao Endo

  Oct. 2016, ANNALS OF NEUROLOGY, 80, S200 - S200, English

  Summary international conference


• 【筋ジストロフィー・筋疾患-最近の進歩】 ミオパチーの臨床と研究の最新トピックス 福山型筋ジストロフィーと類縁疾患 リビトールリン酸とアンチセンス核酸

  Kobayashi Kazuhiro, Toda Tatsushi

  医歯薬出版(株), Oct. 2016, 医学のあゆみ, 259(1) (1), 51 - 57, Japanese

  [Invited]

  Introduction scientific journal


• Ο-マンノース型糖鎖上に形成されるリビトールリン酸のタンデム構造とその生合成機構

  萬谷 博, 金川 基, 小林 千浩, 田尻 道子, 久我 敦, 山口 芳樹, 赤阪 啓子[萬谷], 古川 潤一, 水野 真盛, 川上 宏子, 篠原 康郎, 和田 芳直, 戸田 達史, 遠藤 玉夫

  (公社)日本生化学会, Sep. 2016, 日本生化学会大会プログラム・講演要旨集, 89回, [3T08 - 062)], Japanese


• γセクレターゼによるAPP-CTFβのγ切断部位を調節する内在性分子の解析

  岩田 修永, 松尾 和哉, 森田 知樹, 渡辺 かおり, 八田 大典, 浅井 将, 八幡 直樹, 近藤 孝之, 井上 治久, 関 恒慶, 小林 千浩, 戸田 達史, 城谷 圭朗

  (公社)日本生化学会, Sep. 2016, 日本生化学会大会プログラム・講演要旨集, 89回, [2P - 355], Japanese


• FukutinはLARGE発現による筋ジストロフィーの軽減に必須である(Fukutin is prerequisite to ameliorate muscular dystrophy by LARGE expression)

  大塚 喜久, 金川 基, 游 智傑, 伊藤 千代美, 千代 智子, 小林 千浩, 岡田 尚巳, 武田 伸一, 戸田 達史

  (一社)日本神経学会, Dec. 2015, 臨床神経学, 55(Suppl.) (Suppl.), S213 - S213, English


• 福山型先天性筋ジストロフィーのアンチセンス治療における至適薬剤の選択

  Ikeda Mariko, 小林 千浩, 佐藤 洋平, 若山 達志, 増田 博文, 竹島 泰弘, 飯島 一誠, Toda Tatsushi

  (株)診断と治療社, Mar. 2015, 小児科診療, 78(3) (3), 409 - 409, Japanese

  [Refereed][Invited]

  Meeting report


• 福山型先天性筋ジストロフィーのアンチセンス治療における至適薬剤の選択

  池田 真理子, 佐藤 洋平, 若山 達志, 増田 博文, 小林 千浩, Morioka Ichiro, 飯島 一誠, 戸田 達史

  (公社)日本小児科学会, Feb. 2015, 日本小児科学会雑誌, 119(2) (2), 240 - 240, Japanese


• 福山型先天性筋ジストロフィーにおけるバイオマーカーの検索

  池田真理子, 池田真理子, 運崎愛, 粟野宏之, 李知子, 竹島泰弘, 小林千浩, 森岡一朗, 飯島一誠, 戸田達史

  2015, 日本人類遺伝学会大会プログラム・抄録集, 60th, 226, Japanese


• パーキンソン病感受性遺伝子α-synuclein SNPとnoncoding RNA

  水田 依久子, 佐竹 渉, 村山 繁雄, 金川 基, 小林 千浩, 高藤 和輝, 永森 收志, 山本 光利, 服部 信孝, 村田 美穂, 金井 好克, 水野 敏樹, 中川 正法, 戸田 達史

  (一社)日本神経学会, Dec. 2014, 臨床神経学, 54(Suppl.) (Suppl.), S24 - S24, Japanese


• LARGEによる先天性筋ジストロフィーモデルマウスへの遺伝子治療

  大塚 喜久, 金川 基, 伊藤 千代美, 游 智傑, 千代 智子, 小林 千浩, 岡田 尚巳, 武田 伸一, 戸田 達史

  (一社)日本神経学会, Dec. 2014, 臨床神経学, 54(Suppl.) (Suppl.), S212 - S212, Japanese


• 遺伝学的解析により診断確定した遺伝性筋疾患家系におけるLaing遠位型ミオパチー

  小田 哲也, 小林 千浩, 熊 暉, 佐竹 渉, 鈴木 穣, 菅野 純夫, 戸田 達史

  (一社)日本神経学会, Dec. 2014, 臨床神経学, 54(Suppl.) (Suppl.), S258 - S258, Japanese


• 神経系細胞分化過程の遺伝子解析によるアルツハイマー病病態制御遺伝子の検索

  関恒慶, 小林千浩, 八幡直樹, 浅井将, 岩田修永, 井上治久, 戸田達史

  (一社)日本神経学会, Dec. 2014, 55th Annual Meeting of the Japanese Society of Neurology, Fukuoka., 54(Suppl.) (Suppl.), S50 - S50, Japanese


• A de novo mutation of the MYH7 gene in a large Chinese family with autosomal dominant myopathy

  T. Toda, H. Xiong, T. Oda, K. Kobayashi, S. Wang, W. Satake, H. Jiao, Y. Yang, Y. Suzuki, S. Sugano, X. Wu

  Oct. 2014, NEUROMUSCULAR DISORDERS, 24(9-10) (9-10), 811 - 811, English

  Summary international conference


• 福山型先天性筋ジストロフィーのアンチセンス治療における至適薬剤の選択

  Ikeda Mariko, 小林 千浩, 佐藤 洋平, 若山 達志, 増田 博文, 竹島 泰弘, 飯島 一誠, Toda Tatsushi

  (一社)日本小児神経学会, May 2014, 脳と発達, 46(Suppl.) (Suppl.), S314 - S314, Japanese

  [Refereed]

  Meeting report


• 2種類のフクチン欠損マウスを用いた福山型筋ジストロフィーの病態解析と遺伝子治療

  金川 基, 游 智傑, 伊藤 千代美, 深田 宗一朗, 千代 智子, 小林 千浩, 岡田 尚巳, 武田 伸一, 戸田 達史

  (公社)日本生化学会, Sep. 2013, 日本生化学会大会プログラム・講演要旨集, 86回, 2P - 033, Japanese


• iPS細胞技術を用いた神経疾患研究の進歩と今後の展望 神経分化過程におけるAβ40とAβ42の産生比の変化とその責任遺伝子の解析

  浅井 将, 中野 梨絵, 荒木 希, 渡邊 かおり, 八幡 直樹, 関 恒慶, 小林 千浩, 戸田 達史, 城谷 圭朗, 井上 治久, 岩田 修永

  (公社)日本生化学会, Sep. 2013, 日本生化学会大会プログラム・講演要旨集, 86回, 3S15a - 3, Japanese


• 【検査値を読む2013】 遺伝子・染色体検査 先天性遺伝子検査 福山型筋ジストロフィー遺伝子

  Kobayashi Kazuhiro, Toda Tatsushi

  (株)南江堂, Jun. 2013, 内科, 111(6) (6), 1087 - 1087, Japanese

  [Invited]

  Introduction commerce magazine


• 福山型筋ジストロフィーの新たな病態と分子標的治療

  Toda Tatsushi, Ikeda Mariko, 小林 千浩

  (株)診断と治療社, Apr. 2013, 小児科診療, 76(4) (4), 671 - 671, Japanese

  [Invited]

  Introduction commerce magazine


• 福山型筋ジストロフィー 遺伝子・病態の解明、分子標的治療を目指して

  Toda Tatsushi, 谷口 真理子, Kanagawa Motoi, Kobayashi Kazuhiro

  (公社)日本生化学会, Apr. 2013, 生化学, 85(4) (4), 253 - 260, Japanese

  [Invited]

  Introduction other


• 常染色体優性遺伝形式をとる筋疾患の中国人大家系における遺伝学的解析

  小田 哲也, 小林 千浩, 佐竹 渉, 熊 暉, 戸田 達史

  (一社)日本神経学会, Dec. 2012, 臨床神経学, 52(12) (12), 1403 - 1403, Japanese


• フクチン関連蛋白(FKRP)はαジストログリカンのポストリン酸修飾に関与する

  久我 敦, 金川 基, 首藤 篤史, 小林 千浩, Chan Y.M., Lu Q.L., 戸田 達史

  (一社)日本神経学会, Dec. 2012, 臨床神経学, 52(12) (12), 1624 - 1624, Japanese


• ジストログリカンに見出された新規糖鎖修飾体の生理機能と筋ジストロフィー病態への関与

  金川 基, 伊藤 千代美, 深田 宗一朗, 游 智傑, 久我 敦, 小林 千浩, 戸田 達史

  (公社)日本生化学会, Dec. 2012, 日本生化学会大会プログラム・講演要旨集, 85回, 3T15 - 02, Japanese


• ここまで分かった筋疾患 福山型筋ジストロフィーの分子標的治療

  戸田 達史, 谷口 真理子[池田], 小林 千浩

  (一社)日本神経学会, Nov. 2012, 臨床神経学, 52(11) (11), 1158 - 1158, Japanese


• Fukutin-related protein (FKRP) is involved in the post-phosphoryl modification of alpha-dystroglycan

  A. Kuga, M. Kanagawa, A. Sudo, Y. M. Chan, M. Tajiri, H. Manya, K. Kobayashi, T. Endo, Q. L. Lu, Y. Wada, T. Toda

  Oct. 2012, NEUROMUSCULAR DISORDERS, 22(9-10) (9-10), 815 - 815, English

  Summary international conference


• 【神経筋疾患の分子標的治療開発】 福山型筋ジストロフィーの分子標的治療

  Toda Tatsushi, Ikeda Mariko, Kobayashi Kazuhiro

  (株)北隆館, Sep. 2012, BIO Clinica, 27(10) (10), 925 - 929, Japanese

  [Invited]

  Introduction scientific journal


• MEDICAL TOPICS(第42回) 福山型筋ジストロフィーのスプライシング異常に対するアンチセンス治療

  Ikeda Mariko, Ikeda Mariko, Kobayashi Kazuhiro, Toda Tatsushi

  (株)メディカルレビュー社, May 2012, THE LUNG-perspectives, 20(2) (2), 186 - 191, Japanese

  [Invited]

  Introduction scientific journal


• 福山型筋ジストロフィーの病的スプライシング異常とアンチセンス療法

  Ikeda Mariko, Kobayashi Kazuhiro, Toda Tatsushi

  Apr. 2012, 実験医学, 30(6) (6), 950 - 953, Japanese

  [Invited]

  Introduction scientific journal


• 【遺伝性筋疾患の新たな治療戦略】 福山型筋ジストロフィーの新たな病態とアンチセンス療法

  Toda Tatsushi, Ikeda Mariko, Kobayashi Kazuhiro

  (有)科学評論社, Apr. 2012, 神経内科, 76(4) (4), 361 - 366, Japanese

  [Invited]

  Introduction scientific journal


• 福山型筋ジストロフィーのSVA挿入によるスプライシング異常とレスキュー

  谷口 真理子[池田], 小林 千浩, 金川 基, 遊 智傑, 小田 哲也, 久我 敦, 倉橋 浩樹, 武田 伸一, 戸田 達史

  (公社)日本小児科学会, Feb. 2012, 日本小児科学会雑誌, 116(2) (2), 264 - 264, Japanese


• ジストログリカンに見出された新規糖鎖修飾による機能制御と病態

  金川基, 久我敦, 首藤篤史, 田尻道子, 萬谷博, 吉川大和, 野水基義, 小林千浩, 遠藤玉夫, 和田芳直, 戸田達史

  2012, 日本糖質学会年会要旨集, 31st


• フクチン変異筋ジストロフィーにみられるミスセンス変異体の局在異常とジストログリカン糖鎖修飾活性、およびクルクミンによる是正

  立川 雅司, 金川 基, 游 智傑, 小林 千浩, 戸田 達史

  (公社)日本生化学会, Sep. 2011, 日本生化学会大会プログラム・講演要旨集, 84回, 2T8a - 9, Japanese


• An alpha-synuclein 3 '-flanking region SNP interacts with Parkinson's disease susceptibility via allele-specific binding of a transcription factor

  I. Mizuta, W. Satake, K. Takafuji, M. Kanagawa, K. Kobayashi, S. Nagamori, Y. Kanai, M. Yamamoto, N. Hattori, M. Murata, T. Toda

  May 2011, MOVEMENT DISORDERS, 26, S313 - S314, English

  Summary international conference


• 筋ジストロフィーの原因となるミスセンス変異フクチンの細胞内局在変化

  立川 雅司, 金川 基, 小林 千浩, 戸田 達史

  (公社)日本生化学会, Dec. 2010, 日本生化学会大会・日本分子生物学会年会合同大会講演要旨集, 83回・33回, 4T6 - 10, Japanese


• 認知能力と社会・脳・遺伝子 : 双生児の類似性から(自主企画(3))

  敷島 千鶴, 安藤 寿康, 杉本 雄太郎, 鈴木 国威, 小林 千浩

  日本パーソナリティ心理学会, 10 Oct. 2010, 日本パーソナリティ心理学会大会発表論文集, 0(19) (19), 15 - 16, Japanese


• Disruption of dystroglycan-pikachurin interaction underlies the molecular pathogenesis of eye abnormalities in dystroglycanopathy

  M. Kanagawa, Y. Omori, K. Kobayashi, Y. Miyagoe-Suzuki, S. Takeda, T. Endo, T. Furukawa, T. Toda

  Oct. 2010, NEUROMUSCULAR DISORDERS, 20(9-10) (9-10), 600 - 600, English

  Summary international conference


• Some of disease-causing missense fukutin mutants mislocalize to endoplasmic reticulum

  M. Tachikawa, M. Kanagawa, K. Kobayashi, T. Toda

  Oct. 2010, NEUROMUSCULAR DISORDERS, 20(9-10) (9-10), 600 - 600, English

  Summary international conference


• 認知能力の差が顕著な一卵性双生児の分子遺伝学的解析

  小林千浩, 古川真理, 游智傑, 敷島千鶴, 瀬々潤, 菅原祐子, 岩本和也, 加藤忠史, 安藤寿康, 戸田達史

  2010, 日本人類遺伝学会大会プログラム・抄録集, 55th


• Residual laminin-binding activity and enhanced dystroglycan glycosylation by LARGE in novel model mice to dystroglycanopathy

  M. Taniguchi, M. Kanagawa, S. Takeda, S. Yuko Miyagoe-Suzuki, S. Takeda, T. Endo, K. Kobayashi, K. P. Campbell, T. Toda

  Sep. 2009, NEUROMUSCULAR DISORDERS, 19(8-9) (8-9), 599 - 599, English

  Summary international conference


• ジスフェリン介在細胞膜修復システムは糖鎖付加欠損筋ジストロフィーと関係がある(Involvement of dysferlin-mediated membrane repair system in progression of glycosylation-defect muscular dystrophy)

  Lu Zhongpeng, 金川 基, 立川 雅司, 谷口 真理子, 小林 千浩, 戸田 達史

  (公社)日本生化学会, Sep. 2009, 日本生化学会大会プログラム・講演要旨集, 82回, 4P - 033, English


• FCMD発症にかかわるフクチンミスセンス変異体の細胞内局在とPOMGnT1との結合の観察

  立川 雅司, 金川 基, 小林 千浩, 戸田 達史

  (公社)日本生化学会, Sep. 2009, 日本生化学会大会プログラム・講演要旨集, 82回, 4P - 149, Japanese


• 【認知症のゲノミクス】 認知と遺伝子

  Kobayashi Kazuhiro, 戸田 達史

  (株)メディカルレビュー社, Jul. 2008, Cognition and Dementia, 7(3) (3), 243 - 251, Japanese

  [Invited]

  Introduction scientific journal


• Searching for the causative mutation of 16q22 1-linked autosomal dominant cerebellar ataxia

  Takeshi Amino, Kinya Ishikawa, Nozomu Sato, Taro Ishiguro, Kazuhiro Kobayashi, Tatsushi Toda, Shuichi Asakawa, Nobuyoshi Shimizu

  2008, NEUROSCIENCE RESEARCH, 61, S267 - S267, English

  Summary international conference


• フクチンはMEB病原因糖転位酵素POMGnT1と結合し活性に影響する

  戸田 達史, 熊 暉, 小林 千浩, 立川 雅司, 千代延 友裕, 萬谷 博, 遠藤 玉夫

  (一社)日本神経学会, Dec. 2006, 臨床神経学, 46(12) (12), 1052 - 1052, Japanese


• 16番染色体長腕連鎖型優性遺伝性小脳皮質萎縮症(16q-ADCCA)の臨床・病理・遺伝的特徴

  石川 欽也, 融 衆太, 常深 泰司, 大和田 潔, 石田 玄, 吉田 真理, 橋詰 良夫, 村山 繁雄, 水谷 俊雄, 小林 千浩, 近藤 郁子, 戸田 達史, 水澤 英洋

  (一社)日本神経学会, Dec. 2005, 臨床神経学, 45(12) (12), 1078 - 1078, Japanese


• Fukutin interacts with and modulates POMGnT1

  T Toda, H Xiong, K Kobayashi, M Tachikawa, T Chiyonobu, Y Nagai, H Manya, T Endo

  Oct. 2005, NEUROMUSCULAR DISORDERS, 15(9-10) (9-10), 716 - 716, English

  Summary international conference


• Fukutin and α-dystroglycanopahties

  Tatsushi Toda, T. Chiyonobu, H. Xiong, M. Tachikawa, K. Kobayashi, H. Manya, S. Takeda, M. Taniguchi, H. Kurahashi, T. Endo

  Oct. 2005, Acta Myologica, 24(2) (2), 60 - 63, English

  [Refereed]

  Introduction scientific journal


• フクチンの構造と機能の解析

  小林 千浩, 立川 雅司, 萬谷 博, 藤掛 伸宏, 熊 暉, 大野 耕策, 遠藤 玉夫, 戸田 達史

  (一社)日本神経学会, Dec. 2004, 臨床神経学, 44(12) (12), 1209 - 1209, Japanese


• 【神経糖鎖生物学】 糖鎖と神経・筋疾患,病態モデル 福山型先天性筋ジストロフィーとαジストログリカノパチー

  Kobayashi Kazuhiro, 戸田 達史

  共立出版(株), Nov. 2004, 蛋白質・核酸・酵素, 49(15) (15), 2457 - 2462, Japanese

  [Invited]

  Introduction scientific journal


• フクチンのゴルジ局在とαジストログリカンへの関与

  小林 千浩, 谷口 妃代美, 立川 雅司, 藤掛 伸宏, 鹿野 博亀, 佐々木 淳子, 倉橋 浩樹, 村上 龍文, 砂田 芳秀, 新井 謙, 松村 喜一郎, 萬谷 博, 遠藤 玉夫, 戸田 達史

  (一社)日本神経学会, Dec. 2003, 臨床神経学, 43(12) (12), 1057 - 1057, Japanese


• Loss-of-function of an N-acetylglucosaminyltransferase, POMGnT1, in muscle-eye-brain disease.

  K Kobayashi, H Manya, T Toda, T Endo

  Nov. 2003, AMERICAN JOURNAL OF HUMAN GENETICS, 73(5) (5), 544 - 544, English

  Summary international conference


• Mild muscle-eye-brain disease is compatible with preserved vision and normal-appearing supra- but not infratentorial brain structures on MRI

  A Steinbrecher, J Vajsar, U Grieben, J Sperner, Straub, V, K Kobayashi, R Herrmann, T Toda, T Voit

  Sep. 2003, NEUROMUSCULAR DISORDERS, 13(7-8) (7-8), 637 - 637, English

  Summary international conference


• O-Man型糖鎖不全と神経細胞遊走異常を伴う先天性筋ジストロフィー(Mammalian O-mannosyl glycan and relationship to muscular dystrophy and neuronal migration disorder)

  遠藤 玉夫, 萬谷 博, 小林 千浩, 谷口 妃代美, 戸田 達史

  日本神経化学会, Aug. 2003, 神経化学, 42(2-3) (2-3), 283 - 283, English


• 【糖鎖の新たな機能と疾患へのかかわり】 糖鎖と筋ジストロフィー

  Kobayashi Kazuhiro, 戸田 達史

  (株)中山書店, Aug. 2003, Molecular Medicine, 40(9) (9), 1070 - 1076, Japanese

  [Invited]

  Introduction scientific journal


• 筋ジストロフィーに関連する疾患の病態解明と治療法の開発に関する研究 フクチンのゴルジ体局在とαジストログリカンへの関与

  戸田 達史, 小林 千浩, 谷口 妃代美, 立川 雅司, 藤掛 伸宏, 鹿野 博亀, 佐々木 淳子, 倉橋 浩樹, 村上 龍文, 砂田 芳秀, 新井 謙, 松村 喜一郎, 萬谷 博, 遠藤 玉夫

  国立精神・神経センター, Jun. 2003, 厚生労働省精神・神経疾患研究委託費研究報告集, 平成14年度, 575 - 575, Japanese


• Fukuyama-type congenital muscular dystrophy (FCMD) and alpha-dystroglycanopathy

  Toda T, Kobayashi Kazuhiro, Takeda S, Sasaki J, Kurahashi H, Kano H, Tachikawa M, Wang F, Nagai Y, Taniguchi K, Taniguchi M, Sunada Y, Terashima T, Endo T, Matsumura K

  The Japanese Teratology Society, Jun. 2003, Congenit Anom (Kyoto), 43(2) (2), 97 - 104, English

  [Refereed]

  Introduction scientific journal


• フクチン,フクチン関連蛋白異常による先天性筋ジストロフィー:福山型と関連疾患

  小林 千浩, 戸田 達史

  (株)診断と治療社, Mar. 2003, 小児科診療, 66(3) (3), 538 - 538, Japanese


• ポストゲノム創薬とグライコサイエンス 糖鎖修飾異常による先天性筋ジストロフィー

  遠藤 玉夫, 萬谷 博, 小林 千浩, 戸田 達史

  (公社)日本薬学会, Mar. 2003, 日本薬学会年会要旨集, 123年会(1) (1), 197 - 197, Japanese


• 筋疾患 Muscle-eye-brain病とαジストログリカノパチー

  戸田 達史, 小林 千浩

  (株)中外医学社, Jan. 2003, Annual Review神経, 2003, 255 - 261, Japanese


• Fukuyama-type congenital muscular dystrophy and abnormal glycosylation of α-dystroglycan

  Toda Tatsushi, Kobayashi Kazuhiro, Takeda S, Sasaki J, Kurahashi H, Kano H, Tachikawa M, Wang F, Nagai Y, Taniguchi K, Taniguchi M, Sunada Y, Terashima T, Endo T, Matsumura K

  2003, Basic Appl Myol, 13, 287 - 292, English

  [Refereed]

  Introduction scientific journal


• Fukuyama-type congenital muscular dystrophy and abnormal glycosylation of a-dystroglycan

  Toda T, Kobayashi Kazuhiro, Takeda S, Sasaki J, Kurahashi H, Kano H, Tachikawa M, Wang F, Nagai Y, Taniguchi K, Taniguchi M, Sunada Y, Terashima T, Endo T, Matsumura K

  2003, Basic Appl Myol, 13, 287 - 292, English

  [Refereed]

  Introduction scientific journal


• 【ミオパチーの治療戦略】 フクチン,フクチン関連蛋白異常による先天性筋ジストロフィー 福山型と関連疾患

  Kobayashi Kazuhiro, 戸田 達史

  医歯薬出版(株), Jan. 2003, 医学のあゆみ, 204(3) (3), 207 - 209, Japanese

  [Invited]

  Introduction scientific journal


• 福山型類縁疾患muscle-eye-brain病原因遺伝子としての新規糖転移酵素POMGnT1の同定

  小林 千浩, 吉田 有人, 萬谷 博, 谷口 妃代美, 鹿野 博亀, 三橋 英代, 竹内 誠, 遠藤 玉夫, 戸田 達史

  (一社)日本神経学会, Dec. 2002, 臨床神経学, 42(12) (12), 1224 - 1224, Japanese


• Microsatellite marker-based genome-wide association studies for Parkinson's disease by using the pooled DNA method.

  Y Momose, M Murata, G Tamiya, T Ikuta, A Oka, K Okamoto, K Kobayashi, M Tachikawa, Y Yoshikawa, M Yamamoto, N Hattori, Y Mizuno, Kanazawa, I, H Inoko, T Toda

  Oct. 2002, AMERICAN JOURNAL OF HUMAN GENETICS, 71(4) (4), 432 - 432, English

  Summary international conference


• A worldwide distribution and a broader clinical spectrum of muscle-eye-brain disease: a genotype-phenoltype correlation.

  K Kobayashi, K Taniguchi, K Saito, H Yamauchi, DK Jin, E Parano, RV Coster, H Topaloglu, T Voit, T Endo, T Toda

  Oct. 2002, AMERICAN JOURNAL OF HUMAN GENETICS, 71(4) (4), 519 - 519, English

  Summary international conference


• Prenatal diagnosis in a family with muscle-eye-brain disease

  Straub, V, R Herrmann, S Hertel, K Taniguchi, K Kobayashi, T Toda, T Voit

  Oct. 2002, NEUROMUSCULAR DISORDERS, 12(7-8) (7-8), 743 - 744, English

  Summary international conference


• 【臨床遺伝子学】 神経系疾患の遺伝子学

  永井 義隆, 小林 千浩, 戸田 達史

  (株)最新医学社, Sep. 2002, 最新医学, 57(9月増刊) (9月増刊), 2142 - 2157, Japanese


• Functional Glycomics:糖鎖シグナルによる細胞機能調節とその変異による疾患 O-Man型糖鎖異常と先天性筋ジストロフィー

  遠藤 玉夫, 小林 千浩, 吉田 有人, 萬谷 博, 戸田 達史

  (公社)日本生化学会, Aug. 2002, 生化学, 74(8) (8), 654 - 654, Japanese


• Chimeric mice deficient in fukutin develop neuronal migration disorder and ocular abnormality together with muscular dystrophy

  T Toda, S Takeda, M Kondo, J Sasaki, K Arai, K Misaki, K Kobayashi, T Fukui, M Imamura, T Shimizu, T Fujikado, K Matsumura, T Terashima

  Jul. 2002, JOURNAL OF THE NEUROLOGICAL SCIENCES, 199, S11 - S11, English

  Summary international conference


• Muscle-eye-brain disease caused by mutations in a glycosyltransferase, POMGnT, and selective deficiency of alpha-dystroglycan

  K Kobayashi, K Taniguchi, H Kano, T Toda, A Yoshida, H Manya, T Endo, T Voit, H Topaloglu

  Jul. 2002, JOURNAL OF THE NEUROLOGICAL SCIENCES, 199, S35 - S35, English

  Summary international conference


• Muscle-eye-brain-like disease with abnormal expression of alpha-dystroglycan not caused by mutations in POMGnT1 gene

  A Steinbrecher, R Herrmann, Straub, V, U Grieben, J Sperner, U Eckel, K Taniguchi, K Kobayashi, T Toda, J Vajsar, UM Wewer, T Voit

  Jul. 2002, JOURNAL OF THE NEUROLOGICAL SCIENCES, 199, S105 - S105, English

  Summary international conference


• 【精神・神経疾患とゲノム】筋ジストロフィーの分子遺伝学

  鹿野 博亀, 小林 千浩, 戸田 達史

  (株)メディカルレビュー社, Jun. 2002, ゲノム医学, 2(3) (3), 265 - 272, Japanese


• Deficiency of alpha-dystroglycan in muscle-eye-brain disease (vol 291, pg 1283, 2002)

  H Kano, K Kobayashi, R Herrmann, M Tachikawa, H Manya, Nishino, I, Nonaka, I, Straub, V, B Talim, T Voit, H Topaloglu, T Endo, H Yoshikawa, T Toda

  May 2002, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 293(5) (5), 1579 - 1579, English

  Others


• 神経内科学 Santavuori病原因遺伝子の解明 糖鎖が筋ジストロフィー,神経細胞移動障害に関与

  小林 千浩, 戸田 達史

  医歯薬出版(株), May 2002, 医学のあゆみ, 201(6) (6), 445 - 447, Japanese


• 【筋疾患】福山型先天性筋ジストロフィーの分子生物学 糖鎖,新たな展開

  戸田 達史, 小林 千浩

  (株)医学書院, May 2002, 臨床検査, 46(5) (5), 543 - 547, Japanese


• 筋ジストロフィー及び関連疾患の臨床病態解明と治療法開発に関する研究 福山型先天性筋ジストロフィー遺伝子産物の機能解析と表現型・遺伝子型の研究 FCMD原因遺伝子産物fukutinの機能についての検討

  戸田 達史, 立川 雅司, 小林 千浩, 鹿野 博亀, 佐々木 淳子, 仲山 賢一, 地神 芳文

  国立精神・神経センター, Mar. 2002, 厚生省精神・神経疾患研究委託費による研究報告集, 平成12年度, 395 - 395, Japanese


• 福山型先天性筋ジストロフィー遺伝子産物の機能解析と表現型・遺伝子型の研究

  戸田 達史, 小林 千浩, 佐々木 淳子, 立川 雅司, 鹿野 博亀, 谷口 妃代美, 堀江 正人, 近藤 万里, 武田 聖, 石川 欽也, 仲山 賢一, Voit Thomas, Topaloglu Haluk, 今村 道博, 不二門 尚, 美崎 佳寿代, 寺島 俊雄, 吉田 有人, 萬谷 博, 遠藤 玉夫

  厚生労働省精神・神経疾患研究班, Mar. 2002, 厚生労働省精神・神経疾患研究委託費研究報告書 筋ジストロフィー及び関連疾患の臨床病態解明と治療法開発に関する研究, 平成11〜13年度, 65 - 67, Japanese


• 筋ジストロフィー,神経細胞移動障害に糖鎖が関与する muscle-eye-brain病原因遺伝子の解明

  小林 千浩, 遠藤 玉夫, 戸田 達史

  (株)中山書店, Feb. 2002, Molecular Medicine, 39(3) (3), 338 - 343, Japanese


• 【ゲノムサイエンスの新たなる挑戦】ヒトのゲノム解析 疾患のゲノム解析と解析技術の開発 福山型先天性筋ジストロフィー遺伝子の同定と病態解析

  戸田 達史, 鹿野 博亀, 佐々木 淳子, 立川 雅司, 小林 千浩

  共立出版(株), Dec. 2001, 蛋白質・核酸・酵素, 46(16) (16), 2299 - 2305, Japanese


• 孤発性パーキンソン病のSNPによる大規模候補遺伝子関連解析

  百瀬 義雄, 村田 美穂, 小林 千浩, 金澤 一郎, 戸田 達史

  (一社)日本神経学会, Nov. 2001, 臨床神経学, 41(11) (11), 966 - 966, Japanese


• Association studies of multiple candidate genes for Parkinson's disease by using single nucleotide polymorphisms.

  Y Momose, M Murata, K Kobayashi, M Tachikawa, N Hattori, M Yamamoto, Kanazawa, I, T Toda

  Oct. 2001, AMERICAN JOURNAL OF HUMAN GENETICS, 69(4) (4), 499 - 499, English

  Summary international conference


• Muscular dystrophy and neuronal migration disorder caused by mutations in a novel glycosyltransferase.

  K Kobayashi, A Yoshida, H Manya, M Mamoru, T Inazu, H Mitsuhashi, H Topaloglu, M Takeuchi, T Endo, T Toda

  Oct. 2001, AMERICAN JOURNAL OF HUMAN GENETICS, 69(4) (4), 229 - 229, English

  Summary international conference


• O-Man型糖鎖生合成に関与するヒトOMGnTのクローニングとmuscle-eye-brain(MEB)病原因遺伝子の同定

  吉田 有人, 小林 千浩, 萬谷 博, 水野 真盛, 稲津 敏行, 三橋 英代, Topaloglu Haluk, 竹内 誠, 戸田 達史, 遠藤 玉夫

  (公社)日本生化学会, Aug. 2001, 生化学, 73(8) (8), 698 - 698, Japanese


• ゲノム医科学の現状と展開 ゲノム多型情報を基盤としたパーキンソン病原因遺伝子の同定とオーダーメイド医療の確立へむけて

  戸田 達史, 百瀬 義雄, 小林 千浩, 村田 美穂

  (公社)日本生化学会, Aug. 2001, 生化学, 73(8) (8), 615 - 615, Japanese


• 筋ジストロフィー及び関連疾患の臨床病態解明と治療法開発に関する研究 FCMD遺伝子転写産物の多様なsplicing

  砂田 芳秀, 長谷 麻子, 松村 喜一郎, 清水 輝夫, 佐々木 淳子, 小林 千浩, 戸田 達史

  国立精神・神経センター, Dec. 2000, 厚生省精神・神経疾患研究委託費による研究報告集, 平成11年度, 539 - 539, Japanese


• Neuronal expression of the fukutin gene.

  J Sasaki, K Ishikawa, K Kobayashi, E Kondo-Iida, Y Sakakihara, M Fukayama, H Mizusawa, S Takashima, Y Nakamura, T Toda

  Oct. 2000, AMERICAN JOURNAL OF HUMAN GENETICS, 67(4) (4), 376 - 376, English

  Summary international conference


• フクチン遺伝子の脳における発現の検討

  佐々木 淳子, 石川 欽也, 小林 千浩, 近藤 恵里, 高嶋 幸男, 榊原 洋一, 戸田 達史

  (一社)日本小児神経学会, May 2000, 脳と発達, 32(Suppl.) (Suppl.), S273 - S273, Japanese


• 福山型筋ジストロフィー遺伝子産物フクチンの局在の検討

  小林 千浩, 近藤 恵里, 佐々木 淳子, 中村 祐輔, 戸田 達史

  (一社)日本神経学会, Dec. 1999, 臨床神経学, 39(12) (12), 1322 - 1322, Japanese


• Novel mutations and genotype-phenotype relationships in 107 families with Fukuyama-type congenital muscular dystrophy (FCMD).

  E Kondo-Iida, K Kobayashi, M Watanabe, J Sasaki, Y Nakamura, T Toda

  Oct. 1999, AMERICAN JOURNAL OF HUMAN GENETICS, 65(4) (4), A305 - A305, English

  Summary international conference


• 福山型筋ジストロフィーにおける新たなフクチン遺伝子変異とその表現型について

  近藤 恵里, 小林 千浩, 佐々木 淳子, 斎藤 加代子, 大澤 真木子, 中村 祐輔, 戸田 達史

  (一社)日本小児神経学会, May 1999, 脳と発達, 31(Suppl.) (Suppl.), S141 - S141, Japanese


• 福山型筋ジストロフィーの出生前診断

  高井 泰, 堤 治, 武谷 雄二, 小林 千浩, 戸田 達史

  医歯薬出版(株), Mar. 1999, Journal of Clinical Rehabilitation, 8(3) (3), 240 - 241, Japanese


• 福山型先天性筋ジストロフィー原因遺伝子単離と機能解析に関する研究

  戸田 達史, 小林 千浩, 近藤 恵里, 佐々木 淳子, 中村 祐輔, 斎藤 加代子, 大澤 真木子, 榊原 洋一, 高井 泰, 堤 治, 三宅 正志, 徳永 勝士, 中堀 豊

  厚生省精神・神経疾患研究班, Mar. 1999, 厚生省精神・神経疾患研究委託費研究報告書 筋ジストロフィー及び関連疾患の臨床病態と治療法に関する研究, 平成8〜10年度, 93 - 94, Japanese


• 福山型先天性筋ジストロフィー(FCMD)原因遺伝子の発見

  戸田 達史, 小林 千浩, 中村 祐輔, 金澤 一郎, 徳永 勝士, 中堀 豊

  (一社)日本神経学会, Jan. 1999, 臨床神経学, 39(1) (1), 250 - 250, Japanese


• 【小児の筋ジストロフィーとミオパチー 最近の進歩】福山型先天性筋ジストロフィー

  戸田 達史, 近藤 恵里, 佐々木 淳子, 小林 千浩

  (株)東京医学社, Oct. 1998, 小児内科, 30(10) (10), 1279 - 1284, Japanese


• 【分子筋肉病学】進行性筋ジストロフィー Merosin(laminin subunit M)異常 福山型先天性筋ジストロフィー(FCMD)の分子遺伝学的研究とメロシンの発現異常

  戸田 達史, 小林 千浩

  (株)日本臨床社, Dec. 1997, 日本臨床, 55(12) (12), 3169 - 3175, Japanese

• 誠信心理学辞典[新版] / 分子遺伝学

  Kobayashi Kazuhiro

  Others, 誠信書房, Sep. 2014, Japanese

  Dictionary or encycropedia


• Annual Review神経2003 / Muscle-eye-brain病とαジストログリカノパチー

  戸田達史, Kobayashi Kazuhiro

  Others, 中外医学社, 2003, Japanese

  Scholarly book


• BioScience用語ライブラリー遺伝子病 / X連鎖性痙性対麻痺

  小林千浩, 戸田達史

  羊土社, 1996

• In silico drug screening by using genome-wide association study (GWAS)-data repurposed dabrafenib, an anti-melanoma drug, for Parkinson’s disease

  Takeshi Uenaka, Wataru Satake, Pei-Chieng Cha, Hideki Hayakawa, Kousuke Baba, Shiying Jiang, Kazuhiro Kobayashi, Motoi Kanagawa, Yukinori Okada, Hideki Mochizuki, Tatsushi Toda

  13th International Meeting on Genetic Epidemiology of Parkinson’s Disease, Dec. 2018, English, Paris, International conference

  Poster presentation


• ゲノムワイド関連解析 (GWAS)データを活用したin silico解析による新規抗パーキンソン病薬の同定

  上中 健, SATAKE WATARU, CHA Pei-Chieng, 早川 英規, 馬場 孝輔, KOBAYASHI KAZUHIRO, KANAGAWA MOTOI, 岡田 随象, 望月 秀樹, 戸田 達史

  第41回日本分子生物学会, Nov. 2018, Japanese, 横浜市, Domestic conference

  Poster presentation


• ゲノムワイド関連解析 (GWAS)データを活用したin silico解析による新規抗パーキンソン病薬の探索

  上中 健, SATAKE WATARU, CHA Pei-Chieng, 早川 英規, 馬場 孝輔, KOBAYASHI KAZUHIRO, KANAGAWA MOTOI, 岡田 随象, 望月 秀樹, 戸田 達史

  第91回日本生化学会大会, Sep. 2018, Japanese, 京都市, Domestic conference

  Oral presentation


• ジストログリカノパチ－モデルマウスの中枢神経病態の解析

  首藤 篤史, KANAGAWA MOTOI, 近藤 舞, 伊藤 千代美, KOBAYASHI KAZUHIRO, ENDO MITSUHARU, 南 康博, 饗場 篤, 戸田 達史

  第37回日本糖質学会, Aug. 2018, Japanese, 日本糖質学会, 仙台市, Domestic conference

  Poster presentation


• In silico drug screening identified a novel disease-modifying drug for Parkinson’s disease

  Takeshi Uenaka, Wataru Satake, Pei-Chieng Cha, Hideki Hayakawa, Kousuke Baba, Kazuhiro Kobayashi, Motoi Kanagawa, Yukinori Okada, Hideki Mochizuki, Tatsushi Toda

  第41回日本神経科学大会, Jul. 2018, Japanese, 神戸市, Domestic conference

  Poster presentation


• LARGE Gene Therapy for α-Dystroglycanopathies

  Yoshihisa Ohtsuka, Motoi Kanagawa, Tomoko Chiyo, Kazuhiro Kobayashi, Takashi Okada, Shin’ichi Takeda, Tatsushi Toda

  11th Japanese-French Workshop “New insights in personalized medicine for neuromuscular, Jun. 2018, English, 東京, International conference

  Poster presentation


• ゲノムワイド関連解析 (GWAS)データを活用した in silico 解析による 新規抗パーキンソン病薬の探索

  上中 健, SATAKE WATARU, CHA Pei-Chieng, 早川 英規, 馬場 孝輔, KOBAYASHI KAZUHIRO, KANAGAWA MOTOI, 岡田 随象, 望月 秀樹, 戸田 達史

  第65回 日本生化学会 近畿 支部例会, May 2018, Japanese, 西宮市, Domestic conference

  Oral presentation


• 福山型筋ジストロフィーおよび類縁疾患モデルマウスの中枢神経病態の解析

  首藤 篤史, Kanagawa Motoi, Kobayashi Kazuhiro, Toda Tatsushi

  平成29年度西野班 班会議, Dec. 2017, Japanese, 国立研究開発法人 国立精神・神経医療研究センター, 東京, Domestic conference

  Oral presentation


• 新型の翻訳後修飾体「リビトールリン酸」の同定～修飾機序と筋ジストロフィー病態への関与～

  Kanagawa Motoi, Kobayashi Kazuhiro, 田尻 道子, 萬谷 博, 久我 敦, 山口 芳樹, 和田 芳直, 遠藤 玉夫, Toda Tatsushi

  第39回日本分子生物学会年会, Dec. 2017, Japanese, 日本分子生物学会, 横浜, 糖鎖修飾は様々な生命機能に重要な翻訳後修飾で、その異常は時に重篤な疾患を導く。ジストログリカンは基底膜やシナプス分子の受容体で、糖鎖修飾はリガンド結合活性に不可欠であり、その異常は筋ジストロフィーや滑脳症の原因になる。しかしながら、ジストログリカン糖鎖の構造や修飾酵素の全貌は明らかにされていなかった。今回、我々は、ジストログリカン糖鎖の中に、キシリトール系糖アルコールのリビトールが存在し、リビトールリン酸タンデム構造を形成していることを発見した。更に、筋ジストロフィー原因遺伝子で機能未知であったIsoprenoid synthase domain-containing (ISPD)、フクチン、Fukutin-related protein (FKRP)が、リビトールリン酸修飾に関わる酵素であることを同定した。ISPDはリビトールリン酸の供与体となるC, Domestic conference

  [Invited]

  Nominated symposium


• Dystroglycanopathy is caused by defects of tandem ribitol-phosphate glycosylation

  Kobayashi Kazuhiro

  Consortium of Biological Sciences 2017, Dec. 2017, Japanese, The Molecular Biology Society of Japan, The Japanese Biochemical Society, 神戸, Domestic conference

  [Invited]

  Nominated symposium


• Pathological analysis of central nervous system in dystroglycanopathy mouse models

  首藤 篤史, Kanagawa Motoi, 近藤 舞, Kobayashi Kazuhiro, Endo Mitsuharu, Minami Yasuhiro, Toda Tatsushi

  ConBio2017, Dec. 2017, Japanese, 日本分子生物学会, 日本生化学会, 神戸, Domestic conference

  Oral presentation


• In silico drug screening identified a novel disease-modifying drug for Parkinson’s disease

  Uenaka Takeshi, Satake Wataru, Pei-Chieng Cha, Kobayashi Kazuhiro, Kanagawa Motoi, Hideki Hayakawa, Kousuke Baba, Yukinori Okada, Hideki Mochizuki, Toda Tatsushi

  2017年度生命科学系学会合同年次大会, Dec. 2017, English, 日本分子生物学会, 神戸, Domestic conference

  Poster presentation


• 筋ジストロフィーモデルマウスの中枢神経病態の解析

  首藤 篤史, Kanagawa Motoi, Kobayashi Kazuhiro, Endo Mitsuharu, Minami Yasuhiro, Toda Tatsushi

  第12回 筋ジストロフィー治療研究会, Nov. 2017, Japanese, 不明, 熱海, Domestic conference

  Oral presentation


• Dystroglycanopathy is caused by defects of tandem ribitol-phosphate synthesis

  Kobayashi Kazuhiro, Kanagawa Motoi, 田尻 道子, 萬谷 博, 久我 敦, 山口 芳樹, 和田 芳直, 遠藤 玉夫, Toda Tatsushi

  The 62nd Annual Meeting of the Japan Society of Human Genetics, Nov. 2017, Japanese, The Japan Society of Human Genetics, 神戸, Domestic conference

  Oral presentation


• Pathological analysis of central nervous system in dystroglycanopathy mouse models

  首藤 篤史, Kanagawa Motoi, 近藤 舞, Kobayashi Kazuhiro, Toda Tatsushi

  日本人類遺伝学会 第62回大会, Nov. 2017, Japanese, 日本人類遺伝学会, 神戸, Domestic conference

  Oral presentation


• In silico drug screening identified a novel disease-modifying drug for Pakinson's disease

  Uenaka Takeshi, Satake Wataru, Pei-Chieng Cha, Kobayashi Kazuhiro, Kanagawa Motoi, Hideki Hayakawa, Kousuke Baba, Yukinori Okada, Hideki Mochizuki, Toda Tatsushi

  The 62nd Annual Meeting of the Japan Society of Human Genetics, Nov. 2017, English, The Japan Society of Human Genetics, 神戸, Domestic conference

  Oral presentation


• In silico drug screening identified a novel disease-modifying drug for Parkinson’s disease

  Uenaka Takeshi, Satake Wataru, Pei-Chieng Cha, Kobayashi Kazuhiro, Kanagawa Motoi, Hideki Hayakawa, Kousuke Baba, Yukinori Okada, Hideki Mochizuki, Toda Tatsushi

  The 23rd World Congress of Neurology/ The 58th Annual Meeting of the Japanese Society of Neurology, Sep. 2017, English, World Federation of Neurology/ Japanese Society of Neurology, 京都, International conference

  Poster presentation


• ジストログリカノパチーに対するLARGE遺伝子治療

  Otsuka Yoshihisa, Kanagawa Motoi, 千代智子, Kobayashi Kazuhiro, 岡田尚巳, 武田伸一, Toda Tatsushi

  日本筋学会第3回学術集会, Aug. 2017, Japanese, Japan Muscle Society, 東京, Domestic conference

  Poster presentation


• Identification of a post-translational modification with ribitol-phosphate and its defect in muscular dystrophy: Roles of ISPD, fukutin, and FKRP in a-dystroglycan glycosylation

  Kanagawa Motoi, Kobayashi Kazuhiro, Michiko Tajiri, Hiroshi Manya, Atushi Kuga, Yoshiki Yamaguchi, Yoshinao Wada, Tamao Endo, Toda Tatsushi

  New Directions in Biology and Disease of Skeletal Muscle Conference, Jun. 2017, English, New Directions in Biology and Disease of Skeletal Muscle Conference, オーランド, アメリカ, Glycosylation is an essential post-translational modification that underlies many biological processes and diseases. -dystroglycan (-DG) is a receptor for matrix and synaptic proteins that causes muscular dystrophy and lissencephaly upon its abnormal glycosylation (-dystroglycanopathies). Here we identify the glycan unit ribitol 5-phosphate (Rbo5P), a phosphoric ester of pen, International conference

  Poster presentation


• 新規糖鎖ユニット“リビトールリン酸”の同定と筋ジストロフィーへの関与

  Kanagawa Motoi, Kobayashi Kazuhiro, 田尻 道子, 萬谷 博, 久我 敦, 山口 芳樹, 和田 芳直, 遠藤 玉夫, Toda Tatsushi

  第63回日本生化学会近畿支部例会, May 2017, Japanese, 日本生化学会近畿支部, 神戸, 【目的】ジストログリカン（DG）は、基底膜成分のラミニンやシナプス分子の膜受容体で、リガンドとの結合にはO-マンノース(O-Man)型の糖鎖修飾が必要である。O-Man型糖鎖の末端には、キシロース（Xyl）とグルクロン酸（GlcA）からなるリピート構造があり、直接のリガンド結合部位として機能している。また、O-Man型糖鎖の異常は、ジストログリカン異常症（DG異常症）と総称される筋ジストロフィーの原因になることが知られている。しかし、ジストログリカンの糖鎖構造の全容や、DG異常症原因遺伝子fukutin、fukutin-related protein (FKRP), isoprenoid synthase domain containing (ISPD)などの機能は不明だった。本研究では、DG異常症の発症機序の理解と治療法への道筋を拓くことを目的に、, Domestic conference

  Oral presentation


• Identification of a post-translational modification with ribitol-phosphate and its defect in muscular dystrophy: Roles of ISPD, fukutin, and FKRP in α-dystroglycan glycosylation

  Kanagawa Motoi, Kobayashi Kazuhiro, Michiko Tajiri, Hiroshi Manya, Atsushi Kuga, Yoshiki Yamaguchi, Yoshinao Wada, Tamao Endo, Toda Tatsushi

  Experimental Biology 2017, Apr. 2017, English, ASBMB, Chicago, USA, Glycosylation is an essential post-translational modification that underlies many biological processes and diseases. α-dystroglycan (α-DG) is a receptor for matrix and synaptic proteins that causes muscular dystrophy and lissencephaly upon its abnormal glycosylation (α-dystroglycanopathies). Here we identify the glycan unit ribitol 5-phosphate (Rbo5P), a phosphoric ester of pen, International conference

  Poster presentation


• 糖転移酵素POMGnT1の機能同定と糖鎖認識機構解析

  桑原 直之, 萬谷 博, 山田 健之, 舘野 浩章, Kanagawa Motoi, Kobayashi Kazuhiro, 萬谷(赤阪) 啓子, 弘瀬 友理子, 水野 真盛, 池口 満徳, Toda Tatsushi, 平林 淳, 千田 俊哉, 遠藤 玉夫, 加藤 龍一

  第39回日本分子生物学会年会, Nov. 2016, Japanese, 日本分子生物学会, 横浜, Domestic conference

  [Invited]

  Nominated symposium


• Tandem ribitol-phosphate enables functional glycan formation and its defects cause muscular dystrophy

  Kobayashi Kazuhiro, Kanagawa Motoi, 田尻 道子, 萬谷 博, 久我 敦, 山口 芳樹, 赤阪-萬谷 啓子, 古川 潤一, 水野 真盛, 川上 宏子, 篠原 康郎, 和田 芳直, 遠藤 玉夫, Toda Tatsushi

  The 39th Annual Meeting of the Molecular Biology Society of Japan, Nov. 2016, Japanese, The Molecular Biology Society of Japan, 横浜, Domestic conference

  Poster presentation


• Integration of Leading-edge technologies induces insight into physiology of long noncoding RNA and possibility of therapeutics

  Ikeda Mariko, Kobayashi Kazuhiro, Morioka Ichiro, Iijima Kazumoto, Toda Tatsushi

  第39回日本分子生物学会年会, Nov. 2016, English, 日本分子生物学会, 横浜, Domestic conference

  [Invited]

  Nominated symposium


• Antisense therapy for Fukuyama congenital muscular dystrophy

  Ikeda Mariko, Kobayashi Kazuhiro, Morioka Ichiro, 飯島一誠, 戸田

  日本分子生物学学会, Nov. 2016, Japanese, 日本分子生物学学会, 横浜, Domestic conference

  Oral presentation


• Identification of a Post-Translational Modification with Ribitol-Phosphate and Its Defect in Muscular Dystrophy.

  Toda Tatsushi, Kanagawa Motoi, Kobayashi Kazuhiro, Michiko Tajiri, Hirosi Manya, Atsushi Kuga, Yoshiki Yamaguchi, Yoshinao Wada, Tamao Endo

  The 66th Annual Meeting of the American Society of Human Genetics., Oct. 2016, English, American Society of Human Genetics, バンクーバー, カナダ, International conference

  Poster presentation


• Identification of a Post-Translational Modification with Ribitol-Phosphate and Its Defect in Muscular Dystrophy.

  Toda Tatsushi, Kanagawa Motoi, Kobayashi Kazuhiro, Michiko Tajiri, Hirosi Manya, Atsushi Kuga, Yoshiki Yamaguchi, Yoshinao Wada, Tamao Endo

  141st Annual Meeting of the American Neurological Association, Oct. 2016, English, American Neurological Association, ボルチモア, アメリカ合衆国, International conference

  Poster presentation


• Identification of a Post-translational Modification with Ribitol-Phosphate and Its Defect in Muscular Dystrophy.

  Toda Tatsushi, Kanagawa Motoi, Kobayashi Kazuhiro, Michiko Tajiri, Hirosi Manya, Atsushi Kuga, Yoshiki Yamaguchi, Yoshinao Wada, Tamao Endo

  21st WMS congress 2016, Oct. 2016, English, World Muscle Society, グラナダ, スペイン, International conference

  Oral presentation


• αジストログリカン糖鎖のリビトールリン酸タンデム構造とその生合成経路

  Kobayashi Kazuhiro, Kanagawa Motoi, 田尻 道子, 萬谷 博, 久我 敦, 山口 芳樹, 赤阪-萬谷 啓子, 古川 潤一, 水野 真盛, 川上 宏子, 篠原 康郎, 和田 芳直, 遠藤 玉夫, Toda Tatsushi

  The 3rd Annual Meeting of Japan Muscle Society, Aug. 2016, Japanese, Japan Muscle Society, 東京, Domestic conference

  Poster presentation


• A de novo mutation of the MYH7 gene in a large Chinese family with autosomal dominant myopathy

  Kobayashi Kazuhiro, Tetsuya Oda, Hui Xiong, Satake Wataru, Toda Tatsushi

  The 13th International Congress of Human Genetics, Apr. 2016, English, the East-Asian Union of Human Genetic Societies in conjunction with the Japan Society of Human Genetics, 京都, International conference

  Poster presentation


• 福山型先天性筋ジストロフィーにおけるバイオマーカーの検索

  Ikeda Mariko, 運崎 愛, Hiroyuki Awano, 李 知子, 竹島泰弘, Kobayashi Kazuhiro, Morioka Ichiro, Iijima Kazumoto, Toda Tatsushi

  日本人類遺伝学会 第60回大会, Oct. 2015, Japanese, 日本人類遺伝学会, 東京, Domestic conference

  Oral presentation


• Exome analysis of two families with mental retardation

  Kobayashi Kazuhiro, 千代延 友裕, 森本 昌史, Toda Tatsushi

  The 60th Annual Meeting of the Japanese Society of Human Genetics, Oct. 2015, Japanese, Japanese Society of Human Genetics, 東京, Domestic conference

  Poster presentation


• Fukutin is prerequisite to ameliorate muscular dystrophy by LARGE expression

  Otsuka Yoshihisa, Kanagawa Motoi, 千代 智子, Kobayashi Kazuhiro, 岡田 尚巳, 武田 伸一, Toda Tatsushi

  第34回日本糖質学会年会, Aug. 2015, Japanese, 日本糖質学会, 東京, Dystroglycanopathy is a group of muscular dystrophy caused by abnormal glycosylation of dystroglycan. Here, we explored the conditions needed for successful LARGE gene therapy for dystroglycanopathy. Our data show that myofiber-selective LARGE expression, Domestic conference

  Poster presentation


• Gene therapy study on glycosylation-deficient muscular dystrophy models

  Kanagawa Motoi, Otsuka Yoshihisa, Kobayashi Kazuhiro, 千代 智子, 岡田 尚巳, 武田 伸一, Toda Tatsushi

  第1回日本筋学会学術集会, Aug. 2015, Japanese, 日本筋学会, 東京, 福山型筋ジストロフィーをはじめとする、ジストログリカンの糖鎖異常を発症要因とする疾患群は、ジストログリカノパチーと総称される。我々は、ジストログリカノパチーの病態機序の解明と治療法の開発を目的に、福山型筋ジストロフィーの原因遺伝子フクチンの変異マウスを作出してきた。筋管選択的、筋前駆細胞選択的な２種の異なるコンディショナルノックアウト（cKO）マウスの比較から、細胞膜の脆弱化が発症の引き金になること、筋前駆細胞と筋再生の異常が病態の重篤度に関与することが明らかになった。一方、福山型患者で多くみられるレトロトランスポゾン挿入変異をノックインしたマウスでは、ジストログリカンの糖鎖異常が認められたものの、正常型糖鎖もわずかながら残存しており、発症に至らなかった。これらの疾患モデル研究より明らかになった病態機序を考慮すると、部分的な糖鎖回復でも治療効果が得ら, Domestic conference

  Poster presentation


• 福山型先天性筋ジストロフィーにおける血清中miRNAの発現解析

  Ikeda Mariko, Kobayashi Kazuhiro, 李 知子, 竹島泰弘, Morioka Ichiro, Iijima Kazumoto, Toda Tatsushi

  第57回日本小児神経学会学術集会, May 2015, Japanese, 日本小児神経学会, 大阪, Domestic conference

  Oral presentation


• Fukutin is prerequisite to ameliorate muscular dystrophy by LARGE expression

  Otsuka Yoshihisa, Kanagawa Motoi, 游 智傑, 伊藤 千代美, 千代 智子, Kobayashi Kazuhiro, 岡田 尚巳, 武田 伸一, Toda Tatsushi

  56th Annual Meeting of the Japanese Society of Neurology, May 2015, Japanese, Japanese Society of Neurology, 新潟, Domestic conference

  Oral presentation


• 福山型先天性筋ジストロフィーのアンチセンス治療における至適薬剤の選択

  Ikeda Mariko, 佐藤洋平, 岩山達志, 増田博文, Kobayashi Kazuhiro, Morioka Ichiro, Iijima Kazumoto, Toda Tatsushi

  第118回日本小児科学会学術集会, Apr. 2015, Japanese, 日本小児科学会, 大阪, Domestic conference

  Oral presentation


• 福山型先天性筋ジストロフィーのアンチセンス治療における至適薬剤の選択

  Ikeda Mariko, Kobayashi Kazuhiro, 佐藤 洋平, 若山 達志, 増田 博文, 竹島 泰弘, Iijima Kazumoto, Toda Tatsushi

  第59回日本人類遺伝学会, Nov. 2014, Japanese, 日本人類遺伝学会, 東京, Domestic conference

  Oral presentation


• LARGEによる先天性筋ジストロフィーモデルマウスへの遺伝子治療

  Otsuka Yoshihisa, Kanagawa Motoi, 伊藤 千代美, 游 智傑, 千代 智子, Kobayashi Kazuhiro, 岡田 尚巳, 武田 伸一, Toda Tatsushi

  日本人類遺伝学会第59回大会, Nov. 2014, Japanese, 日本人類遺伝学会, 東京, Domestic conference

  Oral presentation


• Genes regulated by epigenetic mechanisms in determining general intelligence (g) are over-represented in disorders that affect cognition.

  Pei-Chieng Cha, Kobayashi Kazuhiro, Yuko Ando, Keizo Takao, Tsuyoshi Miyakawa, Toda Tatsushi

  The 59th Annual Meeting of The Japanese Society of Human Genetics, Nov. 2014, English, Japanese Society of Human Genetics, Tokyo, Japan, Domestic conference

  Poster presentation


• Genes regulated by epigenetic mechanisms in determining general intelligence (g) are over-represented in disorders that affect cognition.

  Pei-Chieng Cha, Kobayashi Kazuhiro, Yuko Ando, Keizo Takao, Tsuyoshi Miyakawa, Toda Tatsushi

  The 37th Annual Meeting of the Molecular Biology Society of Japan, Nov. 2014, English, American Society of Human Genetics, Yokohama, Japan, Domestic conference

  Poster presentation


• Genes regulated by epigenetic mechanisms in determining general intelligence (g) are over-represented in disorders that affect cognition.

  Pei-Chieng Cha, Kobayashi Kazuhiro, Yuko Ando, Keizo Takao, Tsuyoshi Miyakawa, Toda Tatsushi

  The 64th Annual Meeting of The American Society of Human Genetics,, Oct. 2014, English, American Society of Human Genetics, San Diego, United States of America, International conference

  Poster presentation


• A de novo mutation of the MYH7 gene in a large Chinese family with autosomal dominant myopathy

  Toda Tatsushi, Hui Xiong, Tetsuya Oda, Kobayashi Kazuhiro, Shuo Wang, Satake Wataru, Hui Jiao, Yanling Yang, Yutaka Suzuki, Sumio Sugano, Xiru Wu

  19th international congress of the world muscle society, Oct. 2014, English, world muscle society, ベルリン, ドイツ, International conference

  Poster presentation


• 福山型先天性筋ジストロフィーのアンチセンス治療における至適薬剤の選択

  Ikeda Mariko, Kobayashi Kazuhiro, 佐藤 洋平, 若山 達志, 増田 博文, 竹島 泰弘, Iijima Kazumoto, Toda Tatsushi

  第31回小児神経筋懇話会, Aug. 2014, Japanese, 小児神経筋懇話会, 東京, Domestic conference

  Public symposium


• Impaired viability of muscle precursor cells in muscular dystrophy with glycosylation defects and amelioration of its severe phenotype by limited gene expression

  Kanagawa Motoi, Chih-Chieh Yu, Chiyomi Ito, So-ichiro Fukada, Tomoko Chiyo, Kobayashi Kazuhiro, Takashi Okada, Shin’ichi Takeda, Toda Tatsushi

  The 13th International Congress on Neuromuscular Diseases, Jul. 2014, English, International Congress on Neuromuscular Diseases, 二－ス, フランス, Dystroglycanopathy (DGpathy) is caused by abnormal glycosylation of dystroglycan (DG). To establish effective treatment, we generated 2 distinct conditional knock-out (cKO) mice for fukutin, one of the causative genes for DGpathy. Myofiber-selective fukutin-cKO mice showed mild muscular dystrophy whereas muscle precursor cell (MPC)-selective cKO mice exhibited severe phenotypes, International conference

  Poster presentation


• Impaired viability of muscle precursor cells in muscular dystrophy with glycosylation defects and amelioration of its severe phenotype by limited gene expression

  Kanagawa Motoi, Chih-Chieh Yu, Chiyomi Ito, So-ichiro Fukada, Tomoko Chiyo, Kobayashi Kazuhiro, Takashi Okada, Shin’ichi Takeda, Toda Tatsushi

  The 6th New Directions in Biology and Disease of Skeletal Muscle Conference, Jun. 2014, English, New Directions in Biology and Disease of Skeletal Muscle Conference, シカゴ, 米国, Dystroglycanopathy (DGpathy) is caused by abnormal glycosylation of dystroglycan (DG). To establish effective treatment, we generated 2 distinct conditional knock-out (cKO) mice for fukutin, one of the causative genes for DGpathy. Myofiber-selective fukutin-cKO mice showed mild muscular dystrophy whereas muscle precursor cell (MPC)-selective cKO mice exhibited severe phenotypes, International conference

  Poster presentation


• 福山型先天性筋ジストロフィーのアンチセンス治療における至適薬剤の選択

  Ikeda Mariko, Kobayashi Kazuhiro, 佐藤 洋平, 若山 達志, 増田 博文, 竹島 泰弘, Iijima Kazumoto, Toda Tatsushi

  第56回日本小児神経学会学術集会, May 2014, Japanese, 日本小児神経学会, 浜松, Domestic conference

  Oral presentation


• Genetic analysis of a family with autosomal dominant myopathy

  小田 哲也, Kobayashi Kazuhiro, 熊 暉, Satake Wataru, 鈴木 穣, 菅野 純夫, Toda Tatsushi

  55th Annual Meeting of the Japanese Society of Neurology, May 2014, Japanese, The Japanese Society of Neurology, 福岡, Domestic conference

  Poster presentation


• LARGEによる先天性筋ジストロフィーモデルマウスへの遺伝子治療

  Otsuka Yoshihisa, Kanagawa Motoi, 伊藤 千代美, 游 智傑, 千代 智子, Kobayashi Kazuhiro, 岡田 尚巳, 武田 伸一, Toda Tatsushi

  第55回日本神経学会学術大会, May 2014, Japanese, 日本神経学会, 福岡, Domestic conference

  Poster presentation


• 福山型先天性筋ジストロフィーのアンチセンス治療における至適薬剤の選択

  Ikeda Mariko, Kobayashi Kazuhiro, 佐藤 洋平, 若山 達志, 増田 博文, 竹島 泰弘, Iijima Kazumoto, Toda Tatsushi

  第37回日本小児遺伝学会学術集会, Apr. 2014, Japanese, 日本小児遺伝学会, 名古屋, Domestic conference

  Oral presentation


• 福山型先天性筋ジストロフィーにおける血清中miRNAの発現解析

  Ikeda Mariko, Kobayashi Kazuhiro, Lee Tomoko, 竹島 泰弘, Iijima Kazumoto, Toda Tatsushi

  第117回日本小児科学会学術集会, Apr. 2014, Japanese, 日本小児科学会, 名古屋, Domestic conference

  Oral presentation


• 福山型筋ジストロフィーモデルマウスにおける筋前駆細胞の機能障害

  松尾 恵, Kanagawa Motoi, 伊藤 千代美, Kobayashi Kazuhiro, 深田 宗一朗, Toda Tatsushi

  第36回日本分子生物学会年会, Dec. 2013, Japanese, 日本分子生物学会, 神戸, 筋ジストロフィーは筋の壊死・変性を主病変とし、進行性の筋力低下を伴う遺伝性疾患で、原因遺伝子や遺伝形式等によって多くの病型に分けられる。福山型筋ジストロフィー(FCMD)は、精神遅滞・脳形成不全を伴う重篤な筋ジストロフィーで、本邦における小児期筋ジストロフィーの中では、デュシャンヌ型筋ジストロフィー(DMD)に次いで頻度が高い。我々は以前FCMDの原因遺伝子fukutinを同定した。fukutin変異によって、細胞外マトリックスと細胞骨格を結ぶ膜タンパク質であるジストログリカンの糖鎖に異常が生じ、ラミニンなどの細胞外基質との結合能が低下する。FCMD以外にも糖鎖異常を病因とする筋ジストロフィーが知られており、ジストログリカノパチーと総称されるが、発症機序について不明な点は多い。本研究ではfukutinの生理的役割とジストログリカノパチー病態の解明を目, Domestic conference

  Poster presentation


• Genetic analysis of a family with autosomal dominant myopathy

  Oda Tetsuya, Kobayashi Kazuhiro, 熊 暉, Satake Wataru, 鈴木 穣, 菅野 純夫, Toda Tatsushi

  The 58th Annual Meeting of the Japan Society of Human Genetics, Nov. 2013, Japanese, The Japan Society of Human Genetics, 仙台, Genetic analysis of a family with autosomal dominant myopathy, Domestic conference

  Poster presentation


• Impaired viability of muscle precursor cells in muscular dystrophy with glycosylation defects and amelioration of its severe phenotype by limited gene expression

  Kobayashi Kazuhiro, Kanagawa Motoi, Chih-Chieh Yu, Chiyomi Ito, So-ichiro Fukada, Tomoko Chiyo, Takashi Okada, Shin'ichi Takeda, Toda Tatsushi

  The American Society of Human Genetics 63rd Annual Meething, Oct. 2013, English, The American Society of Human Genetics, Boston, USA, International conference

  Poster presentation


• Impaired viability of muscle precursor cells in muscular dystrophy with glycosylation defects and amelioration of its severe phenotype by limited gene expression

  Kanagawa Motoi, Chih-Chieh Yu, Chiyomi Ito, So-ichiro Fukada, Masako Hozoji-Inada, Tomoko Chiyo, Yuko Miyagoe-Suzuki, Kobayashi Kazuhiro, Takashi Okada, Shin’ichi Takeda, Toda Tatsushi

  18th International Congress of the World Muscle Society, Oct. 2013, English, World Muscle Society, Asilomar, アメリカ, A group of muscular dystrophies, dystroglycanopathy, is caused by abnormalities in post-translational modifications of dystroglycan (DG). To better understand the pathophysiological roles of DG modification and to establish effective treatment for dystroglycanopathy, we generated 2 distinct conditional knock-out (cKO) mice for fukutin, the first dystroglycanopathy gene identifi, International conference

  Poster presentation


• Impaired viability of muscle precursor cells in muscular dystrophy with glycosylation defects and amelioration of its severe phenotype by limited gene expression

  Kanagawa Motoi, Chih-Chieh Yu, Chiyomi Ito, So-ichiro Fukada, Tomoko Chiyo, Kobayashi Kazuhiro, Takashi Okada, Shin'ichi Takeda, Toda Tatsushi

  EMBO Workshop - Molecular Mechanisms of muscle growth and wasting in health and disease, Sep. 2013, English, EMBO Workshop, Ascona, スイス, A group of muscular dystrophies, dystroglycanopathy, is caused by abnormalities in post-translational modifications of dystroglycan (DG). To better understand the pathophysiological roles of DG modification and to establish effective treatment for dystroglycanopathy, we generated 2 distinct conditional knock-out (cKO) mice for fukutin, the first dystroglycanopathy gene identifi, International conference

  Public symposium


• 2種類のフクチン欠損マウスを用いた福山型筋ジストロフィーの病態解析と遺伝子治療

  Kanagawa Motoi, 游 智傑, 伊藤 千代美, 深田 宗一朗, 千代 智子, Kobayashi Kazuhiro, 岡田 尚巳, 武田 伸一, Toda Tatsushi

  第86回日本生化学会大会, Sep. 2013, Japanese, 日本生化学会, 横浜, ジストログリカノパチーと総称される一群の筋ジストロフィーは、ジストログリカンの糖鎖異常によって発症する。本研究では、ジストログリカンに修飾される糖鎖の病態生理的意義の解明と、治療法の開発を目的に、ジストログリカノパチーとして最初に見出された福山型筋ジストロフィーの原因遺伝子フクチンのconditional knock-out （cKO）マウスを2種類作出した。筋線維選択的なMCK-fukutin-cKOマウスは、非常に軽症の筋ジストロフィー病変を示した。未発症のMCK-fukutin-cKOマウスを用いた強制運動負荷実験の結果から、細胞膜の脆弱化が発症の引き金になることが示された。一方、筋前駆細胞選択的なMyf5-fukutin-cKOマウスは、より重篤な病態を示した。単離した筋前駆細胞を用いた増殖・分化実験の結果から、フクチン依存のジストログリカン, Domestic conference

  Oral presentation


• 認知能力の差が顕著な一卵性双生児のDNAメチル化解析と遺伝子発現解析

  Kobayashi Kazuhiro

  思考と行動判断の双生児研究：その現状と展望, May 2013, Japanese, 慶應義塾大学「思考と行動判断」の研究拠点, 東京, Domestic conference

  [Invited]

  Nominated symposium


• Genome-wide DNA methylation and gene expression analyses of monozygotic twins discordant for intelligence levels.

  游 智傑, 古川 真理, Kobayashi Kazuhiro, 敷島 千鶴, 謝 珮琴, 瀬々 潤, 菅原 裕子, 岩本 和也, 加藤 忠史, 安藤 寿康, Toda Tatsushi

  日本双生児研究学会第27回学術講演会, Jan. 2013, Japanese, 日本双生児研究学会, 東京, Human intelligence, as measured by intelligence quotient (IQ) tests, demonstrates one of the highest heritabilities among human quantitative traits. Nevertheless, studies to identify quantitative trait loci responsible for intelligence face challenges bec, Domestic conference

  Oral presentation


• The second most prevalent mutation of fukutin in Japanese Fukuyama muscular dystrophy

  Kobayashi Kazuhiro, 加藤 玲子, 近藤 恵里, 大澤 真木子, 斎藤 加代子, Toda Tatsushi

  The 35th Annual Meeting of the Molecular Biology Society of Japan, Dec. 2012, Japanese, The Molecular Biology Society of Japan, 福岡, Fukuyama muscular dystrophy (FCMD), one of the most common autosomal recessive disorders in Japan, is characterized by congenital muscular dystrophy combined with neuronal migration disorder and ocular abnormalities. Most of the Japanese FCMD patients are, International conference

  Poster presentation


• Identification of genes and pathways regulated by epigenetic mechanisms in determining general intelligence (g) of inbred mice

  チャペイチェン, Kobayashi Kazuhiro, 安藤 祐子, 遊 智傑, 山形 伸二, 岡田 謙介, 瀬々 潤, 高雄 啓三, 宮川 剛, Toda Tatsushi

  Research report of Osaka University Global COE Program Frontier Biomedical Science Underlying Organelle Network Biology, Dec. 2012, English, Osaka University Global COE Program, 淡路島, To study epigenetic regulation of general intelligence (g), 39 inbred mice raised under similar environmental conditions were subjected to five behavioral tests. 11 parameters measuring performance of mice that reflect their cognition were analyzed by usi, Domestic conference

  Poster presentation


• Pathophysiological role of a novel post-translational modification of dystroglycan

  Kanagawa Motoi, 伊藤 千代美, 深田 宗一郎, 游 智傑, Kuga Atsushi, Kobayashi Kazuhiro, Toda Tatsushi

  第85回日本生化学会大会, Dec. 2012, Japanese, 日本生化学会, 福岡, ジストログリカンは、ラミニンなどの基底膜分子の受容体として、様々な組織で機能を発揮する糖タンパク質で、その多様な糖鎖構造の中でも、O-マンノース糖鎖上にリン酸ジエステル結合を介して存在する新規の修飾体（ポストリン酸構造）が、リガンド結合に重要であることが明らかになってきた。一方、脳奇形や精神発達遅滞を伴う先天性筋ジストロフィーの中には、ジストログリカンの糖鎖異常を発症要因とする疾患群が存在する。そのひとつである福山型筋ジストロフィーの原因遺伝子として発見されたフクチンは、ポストリン酸構造の修飾に関与していることが示唆されている。本研究では、フクチン依存的な修飾の生理的・病的意義を明らかにするため、フクチンのconditional knock-out (cKO)マウスを作出した。骨格筋でフクチンを欠損するcKOマウスとして、筋線維選択的なMCK-fuk, Domestic conference

  Oral presentation


• RNA-based mechanism and therapy for muscular dystrophy.

  Toda Tatsushi, Ikeda Mariko, Kobayashi Kazuhiro

  第35回日本分子生物学会年会, Dec. 2012, Japanese, 日本分子生物学会, 福岡, RNA-based mechanism and therapy for muscular dystrophy., Domestic conference

  [Invited]

  Invited oral presentation


• フクチンとFKRPは、ジストログリカンのポストリン酸修飾に関与する

  Kanagawa Motoi, Kuga Atsushi, Tachikawa Masaji, Kobayashi Kazuhiro, Toda Tatsushi

  第7回 筋ジストロフィー治療研究合同発表会, Nov. 2012, Japanese, 筋ジストロフィー治療研究会, 鎌倉, フクチンとFKRPは、ジストログリカンのポストリン酸修飾に関与する, Domestic conference

  Oral presentation


• The second most prevalent mutation of fukutin in Japanese Fukuyama muscular dystrophy

  Kobayashi Kazuhiro, Reiko Kato, Eri Kondo, Makiko Osawa, Kayoko Saito, Toda Tatsushi

  The American Society of Human Genetics 62nd Annual Meething, Nov. 2012, English, The American Society of Human Genetics, San Francisco, USA, Fukuyama muscular dystrophy (FCMD), one of the most common autosomal recessive disorders in Japan, is characterized by congenital muscular dystrophy combined with neuronal migration disorder and ocular abnormalities. Most of the Japanese FCMD patients are homozygous for a founder haplotype that carries the SVA-type retrotransposon insertion mutation in the fukutin gene causing, International conference

  Poster presentation


• Pathogenic exon-trapping by SVA retrotransposon and rescue in Fukuyama muscular dystrophy.

  Ikeda Mariko, Kobayashi Kazuhiro, Kanagawa Motoi, Chih-chieh Yu, Oda Tetsuya, Kuga Atsushi, Hiroki Kurahashi, Hasan O. Akman, Salvatore DiMauro, Toshifumi Yokota, Shin ́ichi Takeda, Toda Tatsushi

  The 62nd Annual Meeting of the American Society of Human Genetics, Nov. 2012, English, American Society of Human Genetics, San Francisco, USA, Pathogenic exon-trapping by SVA retrotransposon and rescue in Fukuyama muscular dystrophy., International conference

  Oral presentation


• Identification of genes and pathways regulated by epigenetic mechanisms in determining general intelligence (g) of inbred mice

  チャペイチェン, Kobayashi Kazuhiro, 安藤 祐子, 遊 智傑, 山形 伸二, 岡田 謙介, 瀬々 潤, 高雄 啓三, 宮川 剛, Toda Tatsushi

  The 62nd Annual Meeting of The American Society of Human Genetics, Nov. 2012, English, The American Society of Human Genetics, San Francisco, California, U.S.A, To study epigenetic regulation of general intelligence (g), 39 inbred mice raised under similar environmental conditions were subjected to five behavioral tests. 11 parameters measuring performance of mice that reflect their cognition were analyzed by usi, International conference

  Poster presentation


• Genome-wide DNA methylation and gene expression analyses of monozygotic twins discordant for intelligence levels.

  Chih-Chieh Yu, Mari Furukawa, Kobayashi Kazuhiro, Chizuru Shikishima, Pei-Chieng Cha, Jun Sese, Hiroko Sugawara, Kazuya Iwamoto, Tadafumi Kato, Juko Ando, Toda Tatsushi

  The American Society of Human Genetics 62nd Annual Meething, Nov. 2012, English, The American Society of Human Genetics, San Francisco, USA, Human intelligence, as measured by intelligence quotient (IQ) tests, demonstrates one of the highest heritabilities among human quantitative traits. Nevertheless, studies to identify quantitative trait loci responsible for intelligence face challenges because of the small effect sizes of individual genes. Phenotypically discordant monozygotic (MZ) twins provide a feasible way t, International conference

  Poster presentation


• The second most prevalent mutation of fukutin in Japanese Fukuyama muscular dystrophy

  Kobayashi Kazuhiro, 加藤 玲子, 近藤 恵里, 大澤 真木子, 斎藤 加代子, Toda Tatsushi

  The 57th Annual Meeting of the Japan Society of Human Genetics, Oct. 2012, Japanese, The Japan Society of Human Genetics, 東京, 福山型筋ジストロフィーは、先天性筋ジストロフィー・II型滑脳症・眼奇形の3症状を示す、我が国に多い常染色体劣性神経筋疾患である。多くの患者は、疾患原因遺伝子であるフクチン遺伝子の3'側非翻訳領域に、スプライシング異常を引き起こす創始者由来のSVA型レトロトランスポゾン挿入変異をホモで持つ。その他の患者は、SVA挿入変異と様々な突然変異の複合ヘテロを示すが、2番目に多く見られるハプロタイプに相当する突然変異はこれまで見つかっていなかった。本研究では、このハプロタイプに、韓国の患者で見つかっているイントロンの点突然変異(c.647+2084G>T)があることを明らかにした。この変異は、エクソン5と6の間の偽エクソンを活性化し、フレームシフトを起こし、完全なフクチンが合成されず、αジストログリカンの糖鎖異常を引き起こしていた。日本と, Domestic conference

  Oral presentation


• Identification of genes and pathways regulated by epigenetic mechanisms in determining general intelligence (g) of inbred mice

  チャペイチェン, Kobayashi Kazuhiro, 安藤 祐子, 遊 智傑, 山形 伸二, 岡田 謙介, 瀬々 潤, 高雄 啓三, 宮川 剛, Toda Tatsushi

  The 57th Annual Meeting of The Japanese Society of Human Genetics, Oct. 2012, English, The Japanese Society of Human Genetics, 東京, To study epigenetic regulation of general intelligence (g), 39 inbred mice raised under similar environmental conditions were subjected to five behavioral tests. 11 parameters measuring performance of mice that reflect their cognition were analyzed by usi, Domestic conference

  Oral presentation


• Fukutin-related protein(FKRP) is involved in the post-phosphoryl modification of alpha-dystroglycan

  Kuga Atsushi, Kanagawa Motoi, Atsushi Sudo, Chan Yiumo Michael, Michiko Tajiri, Hiroshi Manya, Kobayashi Kazuhiro, Tamao Endo, Lu Qi L, Yoshinao Wada, Toda Tatsushi

  17th International Congress of the World Muscle Society, Oct. 2012, English, World Muscle Society, Perth, Australia, Aberrant glycosylation of alpha-DG with reduced laminin-binding activity is a biochemical hallmark of a group of muscular dystrophy commonly referred to as dystroglycanopathy. Among causative genes for dystroglycanopathy, it has been reported that fukuti, International conference

  Poster presentation


• パーキンソン病および認知機能関連分子とパーソナルゲノム解析-常染色体優性遺伝形式をとる神経筋疾患家系における遺伝学的解析

  Oda Tetsuya, Kobayashi Kazuhiro, Satake Wataru, Toda Tatsushi

  新学術領域研究「脳疾患ゲノム情報」平成24年度第1回班会議, Sep. 2012, Japanese, 新学術領域研究「脳疾患ゲノム情報」, 東京, 常染色体優性遺伝形式をとる筋疾患家系でSNPデータを用いた連鎖解析を行い、候補領域を検出した。次世代シークエンサーを用いたエクソーム解析を行い、遺伝子Aの新規ミスセンス変異が疑われる。, Domestic conference

  Oral presentation


• ジストログリカンに見出された新規糖鎖修飾による機能制御と病態

  Kanagawa Motoi, Kuga Atsushi, 首藤篤史, 田尻道子, 萬谷博, 吉川大和, 野水基義, Kobayashi Kazuhiro, 遠藤玉夫, 和田芳直, Toda Tatsushi

  第32回日本糖質学会年会, Sep. 2012, Japanese, 日本糖質学会, 鹿児島, 脳奇形や精神発達遅滞を伴う先天性筋ジストロフィーの中には、ジストログリカンの糖鎖異常を発症要因とする疾患が存在し、それらはジストログリカノパチーと総称されている。ジストログリカンはラミニンやアグリンといった基底膜やシナプス分子の膜受容体であり、そのリガンド結合活性には糖鎖修飾が必須である。リガンド結合や発症に関与する構造として、O-マンノース型糖鎖と、マンノース上にリン酸ジエステル結合を介して存在する新規の修飾体（ポストリン酸構造）が重要であることが明らかになってきた。しかし、ポストリン酸構造の詳細や修飾機序について不明な点は多く残されている。本研究では、複数のジストログリカノパチーのモデルマウスを用いて、ジストログリカノパチー原因遺伝子産物のフクチンとLARGEに加え、FKRPもまたポストリン酸修飾に関与することを新たに明らかにした。また、ジストロ, Domestic conference

  Oral presentation


• 常染色体優性遺伝形式をとる筋疾患の中国人大家系における遺伝学的解析

  Oda Tetsuya, Kobayashi Kazuhiro, Satake Wataru, 熊 暉, Toda Tatsushi

  第53回日本神経学会学術大会, May 2012, Japanese, 日本神経学会, 東京, 常染色体優性遺伝形式をとる筋疾患の中国人大家系において連鎖解析を施行し、候補領域Chr 1q23.3-24.1を同定した。, Domestic conference

  Oral presentation


• Fukutin-related protein(FKRP) is involved in the post-phosphoryl modification of alpha-dystroglycan

  Kuga Atsushi, Kanagawa Motoi, 首藤篤史, Kobayashi Kazuhiro, Chan Y.M, Lu Q.L, Toda Tatsushi

  53rd Annual Meeting of the Japanese Society of Neurology, May 2012, Japanese, The Japanese Society of Neurology, 東京, Aberrant glycosylation of alpha-DG with reduced laminin-binding activity is a biochemical hallmark of a group of muscular dystrophy commonly referred to as dystroglycanopathy. Among causative genes for dystroglycanopathy, it has been reported that fukuti, Domestic conference

  Poster presentation


• 福山型筋ジストロフィーのSVA挿入によるスプライシング異常とレスキュー

  Ikeda Mariko, Kobayashi Kazuhiro, Kanagawa Motoi, 遊 智傑, Oda Tetsuya, Kuga Atsushi, 倉橋浩樹, 武田伸一, Toda Tatsushi

  第115回日本小児科学会学術集会, Apr. 2012, Japanese, Japan Pediatric Society, 福岡, 福山型筋ジストロフィ－(FCMD)は、重度の筋ジストロフィ－に脳奇形を伴う常染色体劣性遺伝性神経筋疾患であり、日本に多く、未だ治療法がない。殆どのFCMD患者は、フクチン遺伝子の3'非翻訳領域に約3kbのSVA型レトロトランスポゾンの挿入変異を持つ。この疾患の発症機序は、mRNAの不安定化や転写障害によるものと考えられていたが、詳細は不明であった。今回我々は、FCMDがSVAの挿入により誘導されるスプライシング異常症であることを証明した。この異常スプライシングは、SVA挿入配列内に存在する強力なスプライシング受容部位のexon-trapping機能により、最終エクソンのフクチンをコードする領域内の選択的スプライシング供与部位が活性化されて、引き起こされていた。そこで、異常スプライシングを阻止するアンチセンスオリゴヌクレオチド(AON)を用い, Domestic conference

  Oral presentation


• Pathogenic exon-trapping by SVA retrotransposon and rescue in Faukuyama muscular dystrophy.

  Ikeda Mariko, Kobayashi Kazuhiro, Kanagawa Motoi, 遊 智傑, Oda Tetsuya, Kuga Atsushi, 倉橋 浩樹, 横田 俊文, 武田 伸一, Toda Tatsushi

  第115回日本小児科学会学術総会, Apr. 2012, Japanese, 日本小児科学会, 福岡, 福山型筋ジストロフィ－(FCMD)は、重度の筋ジストロフィ－に脳奇形を伴う常染色体劣性遺伝性神経筋疾患であり、日本に多く、未だ治療法がない。殆どのFCMD患者は、フクチン遺伝子の3'非翻訳領域に約3kbのSVA型レトロトランスポゾンの挿入変異を持つ。この疾患の発症機序は、mRNAの不安定化や転写障害によるものと考えられていたが、詳細は不明であった。今回我々は、FCMDがSVAの挿入により誘導されるスプライシング異常症であることを証明した。この異常スプライシングは、SVA挿入配列内に存在する強力なスプライシング受容部位のexon-trapping機能により、最終エクソンのフクチンをコードする領域内の選択的スプライシング供与部位が活性化されて、引き起こされていた。そこで、異常スプライシングを阻止するアンチセンスオリゴヌクレオチド(AON)を用い, Domestic conference

  Oral presentation


• 認知能力の差が顕著な一卵性双生児のDNAメチル化解析と遺伝子発現解析

  Chihchieh Yu, Kobayashi Kazuhiro, 安藤 寿康, Toda Tatsushi

  新学術領域平成23年度第2回班会議, Feb. 2012, Japanese, 東京大学神経内科, 東京, Domestic conference

  Oral presentation


• Pathogenic exon-trapping by SVA retrotransposon and rescue in Fukuyama muscular dystrophy

  Kobayashi Kazuhiro, 谷口(池田, 真理子, Kanagawa Motoi, 游 智傑, Oda Tetsuya, Kuga Atsushi, 倉橋 浩樹, 横田 俊文, 武田 伸一, Toda Tatsushi

  第34回日本分子生物学会年会, Dec. 2011, Japanese, 日本分子生物学会, 横浜, Domestic conference

  Oral presentation


• Genome-Wide DNA Methylation and Gene Expression Analyses of Monozygotic Twins Discordant for Intelligence Levels

  Chihchieh Yu, 古川 真理, Kobayashi Kazuhiro, 敷島 千鶴, Pei-Chieng Cha, 瀬々 潤, 菅原 裕子, 岩本 和也, 加藤 忠史, 安藤寿康, Toda Tatsushi

  第34回日本分子生物学会年会, Dec. 2011, English, 日本分子生物学会, 横浜, Domestic conference

  Poster presentation


• Mislocalization of missense fukutin mutants and hypoglycosylation of α-dystroglycan and their correction for treatment of curcumin in fukutin-deficient muscular dystrophy.

  Tachikawa Masaji, Kanagawa Motoi, 游 智傑, Kobayashi Kazuhiro, Toda Tatsushi

  日本人類遺伝学会第56回大会, Nov. 2011, Japanese, 日本人類遺伝学会, 千葉, Domestic conference

  Poster presentation


• Pathogenic exon-trapping by SVA retrotransposon and rescue in Fukuyama muscular dystrophy

  谷口(池田) 真理子, Kobayashi Kazuhiro, Kanagawa Motoi, Chih Chieh Yu, Oda Tetsuya, Kuga Atsushi, 横田 俊文, 倉橋 浩樹, 武田 伸一, Toda Tatsushi

  日本人類遺伝学会第56回大会, Nov. 2011, Japanese, 日本人類遺伝学会, 千葉, Domestic conference

  Oral presentation


• Genome-Wide DNA Methylation and Gene Expression Analyses of Monozygotic Twins Discordant for Intelligence Levels

  Chihchieh Yu, 古川 真理, Kobayashi Kazuhiro, 敷島 千鶴, Pei-Chieng Cha, 瀬々 潤, 菅原 裕子, 岩本 和也, 加藤 忠史, 安藤寿康, Toda Tatsushi

  第56回日本人類遺伝学会, Nov. 2011, English, 日本人類遺伝学会, 千葉, Domestic conference

  Oral presentation


• A genome-wide association study identifies three lociassociated with susceptibility to uterine fibroid

  Cha Pei-Chieng, Atsushi Takahashi, Naoya Hosono, Low Siew-Kee, Kobayashi Kazuhiro, Naoyuki Kamatani, Michiaki Kubo, Toda Tatsushi, Yusuke Nakamura

  日本人類遺伝学会第56回大会, Nov. 2011, English, 日本人類遺伝学会, 千葉, Domestic conference

  Oral presentation


• Pathogenic exon-trapping by SVA retrotransposon and rescue in Fukuyama muscular dystrophy

  谷口(池田) 真理子, Kobayashi Kazuhiro, Kanagawa Motoi, Chih Chieh Yu, Hasan O Akman, Salvatore DiMauro, 横田俊文, 倉橋浩樹, 武田伸一, Toda Tatsushi

  第16回世界筋学会, Oct. 2011, English, 世界筋学会, アルガルベ, ポルトガル, International conference

  Oral presentation


• Dysferlin-mediated membrane repair system contributes to maintenance of skeletal muscle cell viability in mouse models for muscular dystrophy.

  Toda Tatsushi, Kanagawa Motoi, 盧 忠朋, 伊藤 千代美, Kuga Atsushi, 稲田(宝蔵寺, 賢子, 首藤 篤史, Kobayashi Kazuhiro

  第16回世界筋学会, Oct. 2011, English, 世界筋学会, アルガルベ, ポルトガル, International conference

  Poster presentation


• Mislocalization of missense fukutin mutants and hypoglycosylation of α-dystroglycan and their correction for treatment of curcumin in fukutin-deficient muscular dystrophy.

  Tachikawa Masaji, Kanagawa Motoi, 游 智傑, Kobayashi Kazuhiro, Toda Tatsushi

  第84回日本生化学会大会, Sep. 2011, Japanese, 日本生化学会, 京都, Domestic conference

  Oral presentation


• DNA methylation analysis of significantly discordant monozygotic twins for cognitive ability

  Kobayashi Kazuhiro, 古川 真理, 游 智傑, 敷島 千鶴, 瀬々 潤, 菅原 裕子, 岩本 和也, 加藤 忠史, 安藤 寿康, Toda Tatsushi

  第33回日本分子生物学会年会第83回日本生化学会大会合同大会, Dec. 2010, Japanese, 日本分子生物学会 日本生化学会, 神戸, Domestic conference

  Poster presentation


• Some of disease-causing missense fukutin mutants mislocalize to endoplasmic reticurum

  Tachikawa Masaji, Kanagawa Motoi, Kobayashi Kazuhiro, Toda Tatsushi

  第33回日本分子生物学会年会 第83回日本生化学会大会 合同大会, Dec. 2010, Japanese, 日本生化学会・日本分子生物学会, 神戸, Domestic conference

  Oral presentation


• レトロトランスポゾン挿入変異をもつ福山型先天性筋ジストロフィーモデルマウスの創出と糖鎖遺伝子治療

  Kanagawa Motoi, 西本 明美, 千代延 友裕, 鈴木 友子, 武田 伸一, Kobayashi Kazuhiro, Toda Tatsushi

  日本人類遺伝学会第55回大会, Nov. 2010, Japanese, 日本人類遺伝学会, さいたま, Domestic conference

  Poster presentation


• Genome-wide gene expression and DNA methylation analyses of significantly discordant monozygotic twins for cognitive ability

  Kobayashi Kazuhiro, 古川 真理, 游 智傑, 敷島 千鶴, 瀬々 潤, 菅原 裕子, 岩本 和也, 加藤 忠史, 安藤 寿康, Toda Tatsushi

  米国人類遺伝学会第60回年会, Nov. 2010, English, 米国人類遺伝学会, ワシントンDC, アメリカ, International conference

  Poster presentation


• New pathomechanism of Fukuyama-type congenital musucular dystrophy

  谷口 真理子, Kobayashi Kazuhiro, Kanagawa Motoi, 游 智傑, Toda Tatsushi

  第55回日本人類遺伝学会, Oct. 2010, Japanese, 日本人類遺伝学会, 埼玉, Domestic conference

  Oral presentation


• 認知能力の差が顕著な一卵性双生児の網羅的遺伝子発現・DNAメチル化解析

  Kobayashi Kazuhiro

  日本パーソナリティ心理学会第19回大会, Oct. 2010, Japanese, 日本パーソナリティ心理学会, 東京, Domestic conference

  Oral presentation


• 認知能力の差が顕著な一卵性双生児の分子遺伝学的解析

  Kobayashi Kazuhiro, 古川 真理, 游 智傑, 敷島 千鶴, 瀬々 潤, 菅原 裕子, 岩本 和也, 加藤 忠史, 安藤 寿康, Toda Tatsushi

  日本人類遺伝学会第55回大会, Oct. 2010, Japanese, 日本人類遺伝学会, 大宮, Domestic conference

  Oral presentation


• 筋ジストロフィーの原因となるミスセンス変異フクチンの細胞内局在変化

  Tachikawa Masaji, Kanagawa Motoi, Kobayashi Kazuhiro, Toda Tatsushi

  日本人類遺伝学会第55回大会, Oct. 2010, Japanese, 日本人類遺伝学会, さいたま, Domestic conference

  Poster presentation


• Some of disease-causing missense fukutin mutants mislocalize to endoplasmic reticuｌum

  Tachikawa Masaji, Kanagawa Motoi, Kobayashi Kazuhiro, Toda Tatsushi

  15th International congress of the world muscle society, Oct. 2010, English, World Muscle Society, 熊本, International conference

  Poster presentation


• Disruption of dystroglycan-pikachurin interaction underlies the molecular pathogenesis of eye abnormalities in dystroglycanopathy

  Kanagawa Motoi, 大森 義隆, 佐藤 茂, Kobayashi Kazuhiro, 鈴木 友子, 武田 伸一, 遠藤 玉夫, 古川 貴久, Toda Tatsushi

  The 15th International Congress of World Muscle Society, Oct. 2010, English, World Muscle Soceity, 熊本, International conference

  Poster presentation


• Residual laminin-binding activity and enhanced dystroglycan glycosylation by LARGE in novel model mice to dystroglycanopathy

  Kanagawa Motoi, 西本 明美, 千代延 友裕, 鈴木 友子, 武田 伸一, 遠藤 玉夫, Kobayashi Kazuhiro, Kevin Campbell, Toda Tatsushi

  The 25th International Carbohydrate Symposium, Aug. 2010, English, International Carbohydrate Organization, 千葉, International conference

  Poster presentation


• Rasidual laminin-binding activity and enhanced dystroglRasidual laminin-binding activity and enhanced dystroglycan glycosylation by LARGE in novel model mice to dystroglycanopathy.ycan glycosylation by LARGE in novel model mice to dystroglycanopathy.

  Toda Tatsushi, Kanagawa Motoi, 西本 明美, 千代延 友裕, 鈴木 友子, 武田 伸一, 遠藤 玉夫, Kevin Campbell, Kobayashi Kazuhiro

  12th International Congress on Neuromuscular Diseases, Jul. 2010, English, Congrex Sweden, ナポリ, イタリア, International conference

  Poster presentation


• Post-translational maturation of dystroglycan is necessary for pikachurin binding and ribbon synaptic localization

  Kanagawa Motoi, 大森 義隆, 佐藤 茂, Kobayashi Kazuhiro, 鈴木 友子, 武田 伸一, 遠藤 玉夫, 古川 貴久, Toda Tatsushi

  第28回内藤コンファレンス, Jul. 2010, English, 内藤財団, 葉山, International conference

  Poster presentation


• Residual laminin-binding activity and enhanced dystroglycan glycosylation by LARGE in novel model mice to dystroglycanopathy

  Kanagawa Motoi, 西本 明美, 千代延 友裕, 武田 聖, 鈴木 友子, Fang Wang, 谷口 真理子, Zhongpeng Lu, Tachikawa Masaji, 田島 陽一, 武田 伸一, 遠藤 玉夫, Kobayashi Kazuhiro, Kevin Campbell, Toda Tatsushi

  The Ottawa Conference on New Directions in Biology and Disease of Skeletal Muscle, May 2010, English, H. Lee Sweeney and Elizabeth McNally, オタワ, カナダ, International conference

  Poster presentation


• New Pathomecanism of Fukuyama-type congenital muscular dystrophy

  Ikeda Mariko, Kobayashi Kazuhiro, Kanagawa Motoi, Oda Tetsuya, Toda Tatsushi

  砂田班班会議, Dec. 2009, Japanese, 厚生労働省精神・神経疾患研究委託費, 東京都, Domestic conference

  Oral presentation


• Generation of a model mouse for Fukuyama-type Congenital Muscular Dystrophy

  佐藤 佳乃子, Kanagawa Motoi, 伊藤 千代美, 游 智傑, Ikeda Mariko, Kobayashi Kazuhiro, Toda Tatsushi

  第32回日本分子生物学会大会, Dec. 2009, Japanese, 日本分子生物学会, 横浜, Domestic conference

  Poster presentation


• Genomic analysis of monozygotic twins discordant for cognitive ability

  Kobayashi Kazuhiro, 古川 真理, 游 智傑, 敷島 千鶴, 安藤 寿康, Toda Tatsushi

  第32回日本分子生物学会年会, Dec. 2009, Japanese, 日本分子生物学会, 横浜, Domestic conference

  Poster presentation


• Expression analysis of monozygotic twins discordant for cognitive ability

  古川 真理, Kobayashi Kazuhiro, 游 智傑, 瀬々 潤, 敷島 千鶴, 安藤 寿康, Toda Tatsushi

  第32回日本分子生物学会年会, Dec. 2009, Japanese, 日本分子生物学会, 横浜, Domestic conference

  Poster presentation


• Residual laminin-binding activity and enhanced dystroglycan glycosylation by LARGE in novel model mice to dystroglycanopathy

  Ikeda Mariko, Kanagawa Motoi, 武田 聖, 鈴木 友子, 武田 伸一, 遠藤 玉夫, Kobayashi Kazuhiro, キャンベル ケビン, Toda Tatsushi

  第59回米国人類遺伝学会年会, Oct. 2009, English, 米国人類遺伝学会, ホノルル, アメリカ, International conference

  Poster presentation


• Involvement of dysferlin-mediated membrane repair system in progression of glycosylation-defect muscular dystrophy

  Zhongpeng Lu, Kanagawa Motoi, Tachikawa Masaji, Ikeda Mariko, Kobayashi Kazuhiro, Toda Tatsushi

  第82回日本生化学会大会, Oct. 2009, Japanese, 日本生化学会, 神戸, Domestic conference

  Poster presentation


• Genetic Analysis of Monozygotic Twins Discordant for Cognitive Abilities

  Kobayashi Kazuhiro, 古川 真理, 游 智傑, 敷島 千鶴, 安藤 寿康, Toda Tatsushi

  第59回米国人類遺伝学会年会, Oct. 2009, English, 米国人類遺伝学会, ホノルル, アメリカ, International conference

  Poster presentation


• Subcellular localization and POMGnT1 - binding of fukutin missense mutants which are involved in the onset of FCMD.

  Tachikawa Masaji, Kanagawa Motoi, Kobayashi Kazuhiro, Toda Tatsushi

  第82回日本生化学会大会, Oct. 2009, Japanese, 日本生化学会, 神戸, Domestic conference

  Poster presentation

• 日本生化学会


• 日本筋学会


• 日本分子生物学会


• 日本人類遺伝学会

• ラミニン結合性機能糖鎖を応用した筋ジストロフィーに対する創薬研究

  遠藤 玉夫, 田村 純一, 谷口 敦彦, 小林 千浩

  日本学術振興会, 科学研究費助成事業, 基盤研究(A), 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 01 Apr. 2024 - 31 Mar. 2029


• 福山型筋ジストロフィーを代表とするリビトールリン酸不全型筋ジストロフィーに対する基質補充療法の開発

  国立研究開発法人日本医療研究開発機構, 難治性疾患等実用化研究事業, Apr. 2024 - Mar. 2028, Coinvestigator


• 福山型筋ジス及びDG異常症のアンチセンス核酸、糖鎖補充、AAV治療、胎児治療開発

  戸田 達史, 金川 基, 小林 千浩

  日本学術振興会, 科学研究費助成事業, 基盤研究(A), 東京大学, Apr. 2023 - Mar. 2026


• 福山型筋ジストロフィーおよび類縁疾患の病態解析と治療法・薬効評価法の開発

  小林 千浩

  日本学術振興会, 科学研究費助成事業 基盤研究(B), 基盤研究(B), 神戸大学, 01 Apr. 2022 - 31 Mar. 2025


• Biology of sugar-alcohol modification in glycan

  遠藤 玉夫, 田村 純一, 加藤 龍一, 山口 芳樹, 小林 千浩, 永森 收志

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (S), Grant-in-Aid for Scientific Research (S), Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, 26 Jun. 2019 - 31 Mar. 2024

  本研究では、新たな翻訳後修飾体としてのリビトールリン酸（RboP）の生物学的意義を確立することを目的とする。代表者らは、哺乳類のO-マンノース（Man）型糖鎖にリビトールリン酸が含まれることを発見し、その修飾酵素FKTNとFKRPを同定した。O-Man型糖鎖は構造の特徴によりコアM1、コアM2、コアM3の3タイプに分類され、そのうちコアM3糖鎖のみに2個のRboPのタンデム構造（RboP-RboP）が含まれる。このタンデム構造はRboP転移酵素FKTNとFKRPによりCDP-リビトール（CDP-Rbo）からRboPが転移され形成される。FKTNとFKRPはα-ジストログリカノパチー（先天性筋ジストロフィー症）の原因遺伝子産物であり、コアM3糖鎖の合成不全が主因となる。本年度は、2つめのRboPを転移するFKRPのX線結晶構造の解明に成功し、基質認識機構と患者変異による影響を明らかにした。結晶構造からFKRPは幹領域と触媒領域に分けられ、幹領域を介して四量体を形成していた。FKRPの基質には2つのリン酸基（RboPとManP）が含まれ、基質との共結晶解析から、基質の認識には2分子のFKRPが必要であり、一方の分子の幹領域でManPのリン酸を認識し、もう一方の分子の触媒領域でRboPのリン酸を捕捉することが明らかとなった。さらに、α-ジストログリカノパチー患者の変異（Y88F,S221R,L276I）を導入した変異型FKRPはゲル濾過クロマトグラフィーで低分子量画分に検出され、四量体を形成できないことが示された。変異型FKRPの酵素活性は野生型に比較して顕著に低く、変異による四量体形成の阻害が酵素活性減少の原因となることが示された。


• Pathogenesis and Antisense nucleic acid, glycosylation supplementation, and AAV therapy development forFukuyama muscular dystrophy and related diseases

  戸田 達史, 金川 基, 小林 千浩

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (A), The University of Tokyo, 01 Apr. 2020 - 31 Mar. 2023

  本研究は、日本に多いFCMDをはじめとするジストログリカノパチーの発症原因である、リビトールリン酸修飾にかかわる酵素活性を組織レベルで追求し「リビトールリン酸異常症」という疾患概念を確立し、さらなる病態解析を行う。 当該年度は骨格筋選択的なISPD-cKOマウスを作出し、ジストログリカノパチー患者にみられる生化学的異常と筋ジストロフィー症状を呈することを確認した。更に、遺伝子治療やCDP-リビトール補充療法の有効性についての検討に着手した。生体内でCDP-リビトールを検出する系も確立できた。 またNS-035のGLP前臨床試験を完遂させた。組織移行性など薬物動態には問題がなく、やや高い腎毒性が認められ、改善方法を検討した。医師主導治験のprotocolを作成中である。骨格筋選択的なISPD-cKOマウスを作出し、ジストログリカノパチー患者にみられる生化学的異常と筋ジストロフィー症状を呈することを確認した。更に、遺伝子治療やCDP-リビトール補充療法の有効性についての検討に着手した。生体内でCDP-リビトールを検出する系も確立できた。


• 薬事承認申請をめざした福山型筋ジストロフィーにおけるアンチセンス核酸 NS-035 の 第 1／2 相試験（ステップ２）

  国立研究開発法人日本医療研究開発機構研究費 難治性疾患等実用化研究事業, Apr. 2020 - Mar. 2023, Coinvestigator


• Developmental behavioral genetic study of educational processes and their outcome by the twin method.

  Ando Juko

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B), Grant-in-Aid for Scientific Research (B), Keio University, 01 Apr. 2018 - 31 Mar. 2022

  This study examined genetic and environmental structures that explain individual differences of various psychological and behavioral traits which are formed educationally and socially by behavioral genetic method with twin data consisting of two over-20-year longitudinal cohorts of adolescents and adults and a cohort of web research companies. In the adolescent cohort, we clarified the genetic influence of the environment on cognitive abilities, academic performance, and the dominant hand more concretely and dynamically by controlling genetic factors. The adult cohort clarified the genetic and environmental structure of altruism, educational motives and depression, and genetic and environmental effect on the developmental changes in self-esteem and personality.


• Central Nervous System Involvement of Fukuyama type muscular dystrophy

  Ikeda Mariko

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Fujita Health University, 01 Apr. 2018 - 31 Mar. 2021

  Fukuyama congenital muscular dystrophy (FCMD) is a severe, intractable genetic disease that affects the skeletal muscle, eyes, and brain and is attributed to a defect in alpha dystroglycan glycosylation. We previously established disease models of FCMD such as murine model. However, they did not fully recapitulate the phenotypes observed in human patients. In this study, we generated induced pluripotent stem cells (iPSCs) from a human FCMD patient and differentiated these cells into three-dimensional brain organoids and skeletal muscle. The brain organoids mimicked patient phenotypes not reliably reproduced by existing models, including decreased αDG glycosylation.


• ラミニン統合性機能糖鎖を応用した筋ジストロフィー治療薬の開発

  国立研究開発法人日本医療研究開発機構研究費 次世代治療・診断実現のための創薬基盤技術開発事業（糖鎖利用によ る革新的創薬技術開発事業）, Apr. 2018 - Mar. 2021, Coinvestigator


• パーキンソン病に対する真の意味のオーダーメイド治療を目指した研究

  国立研究開発法人日本医療研究開発機構研究費 ゲノム医療実現推進プラットフォーム事業（先端ゲノム研究開発）, Apr. 2016 - Mar. 2021, Coinvestigator


• Elucidation of pathomecanism for Fukuyama muscular dystrophy and dystroglycanopathy and their drug developmen

  Toda Tatsushi

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A), Grant-in-Aid for Scientific Research (A), 01 Apr. 2017 - 31 Mar. 2020

  As a therapeutic agent for Fukuyama muscular dystrophy, a single candidate sequence showing high activity was found by comprehensive screening of antisense nucleic acids, and toxicity and pharmacokinetics were investigated in GLP grade. The presence or absence of DG sugar chains in the radial glial contributes to the severity of subsequent brain lesions during brain formation in four DG disorder mice. The fukutin gene was introduced into the 12.5 day-old brain by in utero electroporation to prevent the onset of cerebral cortical dysplasia. DG sugar chain deficiency contributes to the pathophysiology of cardiomyopathy due to a reduction in myocardial hypertrophic response to hemodynamic stress and a reduction in contractile force of individual cardiomyocytes. As we found Golgi-microtubule structural abnormalities, reducing microtubule structural abnormalities with microtubule polymerization inhibitors leads to treatment.

  Competitive research funding


• Investigation of molecular pathogenesis and development of therapeutic methods for Fukuyama muscular dystrophy and related diseases

  Kobayashi Kazuhiro

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B), Grant-in-Aid for Scientific Research (B), Kobe University, 01 Apr. 2016 - 31 Mar. 2020, Principal investigator

  In this study, we aimed to delineate the full O-Man glycan structure of a-dystroglycan (a-DG) whose abnormalities cause muscular dystrophy, to clarify the biosynthesis pathway of the glycan, to understand the pathogenesis of neuronal dysfunction of the disease, and to explore its therapeutic possibility. We determined the unknown glycan structure that contained ribitol phosphate. We also identified the functions of four gene proteins such as fukutin that are responsible for muscular dystrophy, and determined the biosynthesis pathway for ribitol phosphate of the glycan. We could not find novel proteins modified with the O-Man glycan or a-DG ligands. Some therapeutic strategies were found to be effective for the disease model cells and mice. Further investigations are required.

  Competitive research funding


• 「薬事承認申請をめざした福山型筋ジストロフィーアンチセンス核酸治療薬の非臨床試 験と自然歴・バイオマーカー探索・治験プロトコール作成

  国立研究開発法人日本医療研究開発機構研究費 難治性疾患等実用化研究事業, Apr. 2017 - Mar. 2020, Coinvestigator


• Integrated behavioral genetic study of educational processes.

  Ando Juko, FUJISAWA Keiko, YAMAGATA Shinji, TODA Tatsushi, TOYODA Atsushi, SOMEYA Yoshiaki

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A), Grant-in-Aid for Scientific Research (A), Keio University, 01 Apr. 2014 - 31 Mar. 2018

  Two longitudinal twin studies, for childhood and adulthood, were conducted. In the children cohort, about 200 pairs of fifth graders(11yrs) answered the questionnaire asking academic abilities, social adaptability and educational environments. 120 pairs were given individual develpmental survey for executive functions and so on. Genetic and environmental stability and changes were found in those traits and rythmic tempo showed an interesting GxE interaction. In the adulthood cohort, about 200 pairs of twins answerd the questionnaire asking social attainment, mental health and so on. Resting state of brain for IQ discrepant monozygotic twin paris (8 pairs) were investigated by fMRI and relationship between brain network in left Inferior Temporal Gyrus and IQ was found. It was also suggested that genetic contribution of prosocial behavior differed according to social situation.


• 医薬品としての薬事承認申請をめざしたアンチセンス核酸による福山型筋ジストロフィー治療薬探索と非臨床試験

  国立研究開発法人日本医療研究開発機構 臨床研究・治験推進研究事業, Apr. 2014 - Mar. 2017, Coinvestigator


• Analysis of the causative glycan for muscular dystrophy and exploration of the therapeutic possibility of its neuronal dysfunction

  Kobayashi Kazuhiro

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research, Grant-in-Aid for Challenging Exploratory Research, Kobe University, 01 Apr. 2014 - 31 Mar. 2016, Principal investigator

  In this study, we aimed to delineate the full O-Man glycan structure of a-dystroglycan (a-DG) whose abnormalities cause muscular dystrophy, to clarify the biosynthesis pathway of the glycan, to understand the pathology of neuronal dysfunction of the disease, and to explore its therapeutic possibility. We determined the unknown glycan structure in part by MS analysis of a large quantity of the purified a-DG recombinant protein. We also identified the functions of some genes that are responsible for muscular dystrophy, and determined the detailed structure of the glycan in part that was synthesized using the gene products by MS and NMR analyses. We could not find a novel protein modified with the O-Man glycan or a novel a-DG ligand. We could not see the phenotype of the model mice by behavioral analysis. We are trying the intracerebral administration of antisense oligonucleotides to the model mice. Further investigations are required.

  Competitive research funding


• Antisense oligonucleotide therapy for Fukuyama type congenital muscular dystrophy

  TANIGUCHI-IKEDA Mariko, KOBAYASHI Kazuhiro

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2012 - 31 Mar. 2015

  Fukuyama type congenital muscular dystrophy (FCMD) is a second common, severe childhood muscular dystrophy in Japan. All patients have ancestral insertion of a SINE-VNTR-Alu retrotransposal element (SVA) into a causative gene fukutin. We previously showed that aberrant mRNA splicing, induced by SVA exon-trapping caused FCMD.In this study, we optimized of the best, single AON for clinical trial. We re-designed AONs precisely around the splice sites and assessed the efficacy for exon trap inhibition of these AONs in FCMD patient cells and model mice. By testing on normal Fukutin production and functional analysis, we finally selected one best candidate AON termed AON-F. We also succeeded in improvement on production efficacy for AON-F. We show the promise of splicing modulation therapy as the first radical clinical treatment for FCMD in the near future.


• Identifying the genetic basis and understanding the molecular mechanisms underlying cognitive function

  KOBAYASHI Kazuhiro

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B), Grant-in-Aid for Scientific Research (B), Kobe University, 01 Apr. 2012 - 31 Mar. 2015, Principal investigator

  In this study, in order to identify genes or gene sets that are associated with cognitive function or intelligence, we planned to perform behavioral, gene expression, and genomic analyses using inbred or outbred mice, gene expression, DNA methylation, and genomic analyses using monozygotic twin pairs discordant for IQ scores, genomic analysis of patients with mental retardation, and gene expression analysis of chimpanzee and human brains. We found several genes and gene sets as candidates for cognition-associated molecules and pathways by the studies of inbred mice and discordant monozygotic twins. We also found mutations in the several genes of the mental retardation patients that are known to cause the disease, and some other genes as candidates for the disease-causative genes. Further investigations are required to understand the molecular mechanisms underlying cognitive function.

  Competitive research funding


• Personal genome analysis of genes for Parkinson's disease and cognitive function

  TODA Tatsushi, KOBAYASHI Kazuhiro, SATAKE Wataru

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), Kobe University, 01 Apr. 2010 - 31 Mar. 2015

  We conducted personal genome analyses with our main focus on Parkinson’s disease and human cognitive function. To detect rare but strong risk factors for Parkinson’s disease, we performed whole-exome sequencing and case-control association studies, and detected in LRRK 2 region 2 SNVs that cause amino acid substitution, which is a moderate risk factor for the disease. We also conducted genome-wide DNA methylation and gene expression analyses using 34 samples from 17 pairs of monozygotic twins discordant intelligently, and detected the differences among the twins with higher IQ and lower IQ in the expressions of several mitochondrial ribosomal protein-coding genes, DNA helicase-related genes, and ion channel-related genes. Also, the exome analysis we performed on a large Chinese family with autosomal dominant myopathy detected a 3-bp in-frame deletion in the MYH7 gene and diagnosed the disease as Laing distal myopathy, which is the first LDM case in East Asia.

  Competitive research funding


• Molecular targeting therapy and pathomechanism for Fukuyama muscular dystrophy and related disorders

  TATSUSHI Toda, KOBAYASHI Kazuhiro, KANAGAWA Motoi, IKEDA Mariko

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A), Grant-in-Aid for Scientific Research (A), Kobe University, 01 Apr. 2011 - 31 Mar. 2014

  Fukuyama muscular dystrophy (FCMD) is the first human disease found to result from ancestral insertion of a SINE-VNTR-Alu (SVA) retrotransposon into a causative gene. Here we show that aberrant mRNA splicing, induced by SVA exon-trapping, underlies the molecular pathogenesis of FCMD. Introduction of antisense oligonucleotides (AONs) targeting the splice acceptor, the predicted exonic splicing enhancer and the intronic splicing enhancer prevented pathogenic exon-trapping by SVA in cells of patients with FCMD and model mice, rescuing normal fukutin mRNA expression and protein production. AON treatment also restored fukutin functions, including O-glycosylation of a-DG and laminin binding by a-DG. Thus, we have discovered in human disease a role for SVA-mediated exon-trapping and demonstrated the promise of splicing modulation therapy as the first radical clinical treatment for FCMD and other SVA-mediated diseases.


• Molecular analyses of genes related to cognitive abilities.

  KOBAYASHI Kazuhiro

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research, Grant-in-Aid for Challenging Exploratory Research, Kobe University, 2011 - 2011, Principal investigator

  We divided the inbred mice into high and low performance groups by behavioral analysis, and we identified some gene sets that showed differential expression between the groups. Using monozygotic twins discordant for IQ scores, we also identified some gene sets that expressed differentially between siblings and one gene that showed differential DNA methylation status. In patients with mental retardation, we detected several known duplication or deletion syndromes and unknown copy number changes, CNVs. These genes and CNVs could be associated with cognitive abilities.

  Competitive research funding


• Elucidation of molecular pathogenesis and development of treatment for muscular dystrophy and neurodevelopmental disorder caused by abnormal glycosylation

  KOBAYASHI Kazuhiro

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (A), Grant-in-Aid for Young Scientists (A), Kobe University, 2009 - 2011, Principal investigator

  The structure of the O-Man type glycan ofα-dystroglycan is still unknown in spite of our many efforts for mass spectrometry. We found that some known proteins involved in the O-Man type glycan synthesis are bound to one another and we are searching for other unknown binding molecules. We showed potential in vivo of the gene therapy by adeno-associaterd viral vector and the antisense therapy for the SVA insertion mutation as treatments ofα-DGpathy. We successfully made central nervous system-specific fukutin-deficient mice, and observed abnormality of the brain.

  Competitive research funding


• 神経細胞での筋ジストロフィー原因遺伝子産物の機能とディスレキシアとの共通発症機構

  小林 千浩

  日本学術振興会, 科学研究費助成事業 萌芽研究, 萌芽研究, 大阪大学, 2007 - 2007

  本研究は、福山型先天性筋ジストロフィー原因遺伝子産物fukutinとmuscle-eye-brain病原因遺伝子産物POMGnT1の、神経細胞移動における神経細胞内での機能解析と新たな糖鎖修飾ターゲット分子の発見を目指し、またディスレキシア関連候補遺伝子産物KIAA0319が、α-dystroglycan以外のfukutinとPOMGnT1の新たなO型糖鎖修飾ターゲットであるかどうかを明らかにする目的で行われた。(1)培養細胞系を用いたKIAA0319の糖鎖の解析:ヒト線維芽細胞由来のMRC5細胞株を用いてKIAA0319を強制発現し、PNGase、シアリダーゼ、O-glycosidaseを用いて糖鎖を処理して解析したところ、O型のムチン型糖鎖が結合していることが判明した。(2)fukutinノックアウトマウスES細胞を用いたKIAA0319の糖鎖の解析:KIAA0319をES細胞で強制発現し、糖鎖修飾状態をウエスタンで比較した。野生型とノックアウトのES細胞間で、α-dystroglycanは大きなバンドサイズの差が見られたが、KIAA0319は差が見られなかった。α-dystroglycanのO型糖鎖を補完すると言われているLARGEを同時に強制発現したところ、α-dystroglycanは大きくバンドが移動したが、KIAA0319は変化が無かった。よって、ES細胞ではKIAA0319はfukutinによる糖鎖修飾は受けていないことが分かった。(3)問題点:KIAA0319は脳特異的な発現が見られるので、神経細胞におけるKIAA0319の糖鎖修飾状態を検討する必要がある。

  Competitive research funding


• 神経細胞移動障害を伴う先天性筋ジストロフイーの分子遺伝子学的病態解析

  小林 千浩

  日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 大阪大学, 2004 - 2004


• 糖鎖異常による先天性筋ジストロフイーの分子生物学的病態解析

  小林 千浩

  日本学術振興会, 科学研究費助成事業 特定領域研究, 特定領域研究, 大阪大学, 2003 - 2004

  糖鎖異常と筋ジストロフィー、神経細胞移動障害の関係を明らかにするために、これまで福山型筋ジストロフィー(FCMD)原因遺伝子産物フクチンとmuscle-eye-brain病(MEB)原因遺伝子産物POMGnT1の機能を解析してきた。 フクチンの糖鎖修飾酵素としての活性を見出すため、フクチン強制発現細胞、あるいはECMD患者の細胞を用い、マンノース転移活性、GlcNAc転移活性、ガラクトース転移活性を測定した。FCMD患者の線維芽細胞において、ガラクトース転移活性が健常コントロールと比較し、若干低下していることがわかった。患者サンプルを増やしてこの活性低下の意義を追求する必要がある。一方で、糖基質およびターゲットとなるタンパク質を明らかにするため、2次元電気泳動システムとBiacoreを用いた測定系を立ち上げた。 POMGnT1遺伝子のマウスの相同遺伝子を単離した。 フクチン遺伝子のキメラマウスについては、作成が完了し、病態解析を行った。一方でコンディショナルノックアウトマウスの作成に向け、ターゲティングベクターを構築した。現在ES細胞に導入し、スクリーニング中である。 国内、海外から福山型筋ジス、muscle-eye-brain病、Walker-Warburg症候群の症例を広く集め、POMGnT1遺伝子の変異の有無を検索した。いくつかの新たな変異を見出し、変異の種類と症状の関係、特に水頭症との緩い関係が見出された。 GalT-I、GalT-II各糖転移酵素遺伝子の変異の有無を検索したが、現在のところ見出されていない。


• 糖鎖異常による先天性筋ジストロフィーの分子生物学的病態解析

  科学研究費補助金, 2003 - 2003

  Competitive research funding


• Molecular analysis of Fukuyama muscular dystrophy and functional analysis of the gene product fukutin.

  KOBAYASHI Kazuhiro

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Osaka University, 2001 - 2002

  Fukuyama-type congenital muscular dystrophy (FCMD) is an autosomal recessive severe muscular dystrophy accompanied by brain malformation, prevalent in Japan. This research was performed for the purpose of making the antibodies specific for the FCMD gene product fukutin, analyzing localization and function of fukutin, and creating the mouse model of this disease. Then the following things were clarified. Although some antibodies were obtained which detect overexpressed fukutin in mammalian cells, these could not detect endogenous fukutin. Since it is supposed that fukutin is a glycosyltransferase from our recent researches and that very small quantity of endogenous fukutin exists in cells like many of known glycosyltransferases, it was thought that detection of the endogenous fukutin by the antibodies cannot be made. That is, it turned out that the analysis is difficult using the fukutin antibodies. Moreover, it was shown that fukutin exists in a Golgi body by the immunohistochemical analysis of mammalian cells overexpressing fukutin, and that is not contradictory to the possibility of being a glycosyltransferase. Mutational analysis was performed in the FCMD patients and some additional mutations were newly discovered. Identification of fukutin-binding proteins is tried by affinity column chromatography using recombinant fukutin and by mass spectrometric analysis. Although some proteins were obtained, we are checking whether these are the actual fukutin-binding proteins. Moreover, another analysis is performed using 2-dimensional electrophoresis, immunoprecipitation, and two-hybrid methods in order to identify the target protein of fukutin as a possible glycosyltransferase and the partner protein of the possible fukutin complex. To create the knock-in mice which carry the retrotransposon insertion in 3'-untranslated region of the fukutin gene, the knock-in vector was constructed and introduced to embryonic stem cells. Muscle-eye-brain disease (MEB) bears a striking resemblance to FCMD, We identified the gene responsible for MEB which encodes POMGnT1 glycosyltransferase.


• 福山型筋ジストロフィーの分子遺伝学的解析と遺伝子産物fukutinの機能解明

  科学研究費補助金, 2001 - 2002

  Competitive research funding


• 福山型筋ジストロフィーの分子遺伝学的解析と遺伝子産物の機能解明

  小林 千浩

  日本学術振興会, 科学研究費助成事業 特別研究員奨励費, 特別研究員奨励費, 東京大学, 1998 - 2000

  Competitive research funding


• Molecular analysis of Fukuyama-type muscular dystrophy and functional analysis of the FCMD gene product fukutin.

  Grant-in-Aid for Scientific Research

  Competitive research funding

• 新規CDP-リビトール誘導体

  金川 基, 戸田 達史, 小林 千浩, 徳岡 秀紀

  特願2020-067017, 02 Apr. 2020, 国立大学法人神戸大学, 特開2021-161092, 11 Oct. 2021, 特許第7510663号, 26 Jun. 2024

  Patent right

  IRI


• 腎毒性軽減剤

  園家 暁, 藤原 佳絵, 佐藤 洋平, 若山 達志, 増田 博文, 関 亮祐, 松原 拓真, 沼倉 佑樹, 岡本 健太郎, 戸田 達史, 池田 真理子, 小林 千浩

  特願2022-555690, 08 Jul. 2022, 日本新薬株式会社, 国立大学法人神戸大学, 特開2023-130288, 20 Sep. 2023, 特許第7471613号, 12 Apr. 2024

  Patent right

  IRI


• ジストログリカン糖鎖修飾異常に伴う疾患の治療剤及び関連酵素測定法

  戸田達史, 小林千浩, 金川基, 遠藤玉夫, 萬谷博, 和田芳直, 田尻道子

  特願2018-534431, 18 Aug. 2017, 特許7058417, 14 Apr. 2022

  Patent right


• 福山型筋ジストロフィー治療用アンチセンス核酸

  TODA TATSUSHI, IKEDA MARIKO, KOBAYASHI KAZUHIRO

  特願2019-075214, 11 Apr. 2019, Kobe University, 日本新薬株式会社, 特開2019‑162111, 特許第6683978号, 31 Mar. 2020

  Patent right


• 福山型筋ジストロフィー治療用アンチセンス核酸

  TODA TATSUSHI, IKEDA MARIKO, KOBAYASHI KAZUHIRO

  特願2014-204750, 11 Jun. 2013, Kobe University, 日本新薬株式会社, 特開2015-91229, 特許第6519842号, 10 May 2019

  Patent right


• Therapeutic agent for diseases associated with abnormalities in dystroglycan sugar chain modification and method for assaying associated enzyme

  TODA,Tatsushi, KOBAYASHI,Kazuhiro, KANAGAWA,Motoi, ENDO,Tamao、MANYA, Hiroshi、WADA, Yoshinao、TAJIRI,Michiko

  特願16/324,194, 18 Aug. 2017, NATIONAL UNIVERSITY CORPORATION KOBE UNIVERSITY, OKYO METROPOLITAN GERIATRIC HOSPITAL AND INSTITUTE OF GERONTOLOGY, OSAKA PREFECTURAL HOSPITAL ORGANIZATION, 特開2020-0188491, 特許US11,040,087

  Patent right


• 福山型筋ジストロフィー治療用医薬組成物

  TODA TATSUSHI, IKEDA MARIKO, KOBAYASHI KAZUHIRO

  特願2012-086891, 05 Apr. 2012, Kobe University, 特開2013-216595, 特許第5943466号, 03 Jun. 2016

  Patent right