Updated on 2024/03/18

写真a

 
MASUDA, Akio
 
Organization
Graduate School of Medicine Center for Neurological Diseases and Cance Division Associate professor
Graduate School
Graduate School of Medicine
Undergraduate School
School of Medicine
Title
Associate professor
Contact information
メールアドレス

Degree 1

  1. 医学博士 ( 2001.9   名古屋大学 ) 

Research Interests 1

  1. Neuron/genome/RNA/splicing

Research Areas 3

  1. Life Science / Medical biochemistry  / Transcription/RNA processing

  2. Others / Others  / Nerve Chemistry/Nerve Pharmacology

  3. Others / Others  / Nerve/Muscular Physiology

Current Research Project and SDGs 2

  1. function of RNA binding protein

  2. Pathology of neurodegenerative diseases

Education 2

  1. Nagoya University   Graduate School, Division of Medical Sciences

    1998.4 - 2001.9

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    Country: Japan

  2. Nagoya University   Faculty of Medicine

    1988.4 - 1994.6

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    Country: Japan

Awards 2

  1. Asian Oceanian Myology Center, Best Poster Award

    2012   Asian Oceanian Myology Center   Global analysis of RNA-binding sites of CUGBP1 and MBNL1 reveal their preferential binding to 3' UTRs to regulate mRNA stability

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    Award type:Award from international society, conference, symposium, etc.  Country:Japan

  2. 北陸製薬・アレルギー学術奨励賞

    2001   財団法人日本アレルギー協会  

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    Country:Japan

 

Papers 88

  1. Position-specific binding of FUS to nascent RNA regulates mRNA length Reviewed

    Masuda A, Takeda J, Okuno T, Okamoto T, Ohkawara B, Ito M, Ishigaki S, Sobue G, Ohno K

    Genes & development   Vol. 29 ( 10 ) page: 1045-57   2015.5

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  2. Calcitriol ameliorates motor deficits and prolongs survival of Chrne-deficient mouse, a model for congenital myasthenic syndrome, by inducing Rspo2.

    Ohkawara B, Tomita H, Inoue T, Zhang S, Kanbara S, Koshimizu H, Miyasaka Y, Takeda JI, Nishiwaki H, Nakashima H, Ito M, Masuda A, Ishiguro N, Ogi T, Ohno T, Imagama S, Ohno K

    Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics   Vol. 21 ( 2 ) page: e00318   2024.1

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    DOI: 10.1016/j.neurot.2024.e00318

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  3. Transcriptome profile of subsynaptic myonuclei at the neuromuscular junction in embryogenesis

    Ohkawara, B; Kurokawa, M; Kanai, A; Imamura, K; Chen, GY; Zhang, RC; Masuda, A; Higashi, K; Mori, H; Suzuki, Y; Kurokawa, K; Ohno, K

    JOURNAL OF NEUROCHEMISTRY     2023.11

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  4. Splicing regulation of GFPT1 muscle-specific isoform and its roles in glucose metabolisms and neuromuscular junction

    Farshadyeganeh, P; Nazim, M; Zhang, RC; Ohkawara, B; Nakajima, K; Rahman, MA; Nasrin, F; Ito, M; Takeda, JI; Ohe, K; Miyasaka, Y; Ohno, T; Masuda, A; Ohno, K

    ISCIENCE   Vol. 26 ( 10 ) page: 107746   2023.10

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  5. FexSplice: A LightGBM-Based Model for Predicting the Splicing Effect of a Single Nucleotide Variant Affecting the First Nucleotide G of an Exon

    Joudaki, A; Takeda, J; Masuda, A; Ode, R; Fujiwara, K; Ohno, K

    GENES   Vol. 14 ( 9 )   2023.9

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  6. Interactions between muscle glucose homeostasis and neuromuscular signal transduction - Lessons learned from lack of a muscle-specific long isoform of GFPT1

    Farshadyeganeh, P; Nazim, M; Ohkawara, B; Masuda, A; Ito, M; Takeda, J; Ohe, K; Ohno, K

    EUROPEAN JOURNAL OF HUMAN GENETICS   Vol. 31   page: 31 - 31   2023.5

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  7. Neural Isoforms of Agrin Are Generated by Reduced PTBP1-RNA Interaction Network Spanning the Neuron-Specific Splicing Regions in <i>AGRN</i>

    Bushra, S; Lin, YN; Joudaki, A; Ito, M; Ohkawara, B; Ohno, K; Masuda, A

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   Vol. 24 ( 8 )   2023.4

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  8. Extremely low-frequency pulses of faint magnetic field induce mitophagy to rejuvenate mitochondria Reviewed

    Takuro Toda, Mikako Ito, Jun-ichi Takeda, Akio Masuda, Hiroyuki Mino, Nobutaka Hattori, Kaneo Mohri, Kinji Ohno

    communications biology   Vol. 5 ( 1 ) page: 453   2022.5

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/s42003-022-03389-7

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  9. Prediction of the splicing effects of SNVs affecting the first nucleotide G of an exon

    Joudaki, A; Takeda, J; Masuda, A; Ohno, K

    EUROPEAN JOURNAL OF HUMAN GENETICS   Vol. 30 ( SUPPL 1 ) page: 498 - 498   2022.4

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  10. Meclozine ameliorates skeletal muscle pathology and increases muscle forces in<i> mdx</i> mice

    Kawamura, Y; Hida, T; Ohkawara, B; Matsushita, M; Kobayashi, T; Ishizuka, S; Hiraiwa, H; Tanaka, S; Tsushima, M; Nakashima, H; Ito, K; Imagama, S; Ito, M; Masuda, A; Ishiguro, N; Ohno, K

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   Vol. 592   page: 87 - 92   2022.2

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  11. tRIP-seq法を用いた微量検体からのRNA修飾部位検出 Invited

    増田章男、河地利彦、大野欽司

    細胞   Vol. 53 ( 14 ) page: 918 - 920   2021.12

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    Authorship:Lead author   Language:Japanese  

  12. Regulated splicing of large exons is linked to phase-separation of vertebrate transcription factors Reviewed

    Kawachi, T; Masuda, A; Yamashita, Y; Takeda, J; Ohkawara, B; Ito, M; Ohno, K

    EMBO JOURNAL   Vol. 40 ( 22 ) page: e107485   2021.11

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  13. Zonisamide upregulates neuregulin-1 expression and enhances acetylcholine receptor clustering at the in vitro neuromuscular junction Reviewed

    Inoue, T; Ohkawara, B; Bushra, S; Kanbara, S; Nakashima, H; Koshimizu, H; Tomita, H; Ito, M; Masuda, A; Ishiguro, N; Imagama, S; Ohno, K

    NEUROPHARMACOLOGY   Vol. 195   page: 108637   2021.9

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  14. Rapidly Growing Protein-Centric Technologies to Extensively Identify Protein-RNA Interactions: Application to the Analysis of Co-Transcriptional RNA Processing Reviewed

    Masuda, A; Kawachi, T; Ohno, K

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   Vol. 22 ( 10 )   2021.5

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  15. Zonisamide ameliorates neuropathic pain partly by suppressing microglial activation in the spinal cord in a mouse model Reviewed

    Koshimizu, H; Ohkawara, B; Nakashima, H; Ota, K; Kanbara, S; Inoue, T; Tomita, H; Sayo, A; Kiryu-Seo, S; Konishi, H; Ito, M; Masuda, A; Ishiguro, N; Imagama, S; Kiyama, H; Ohno, K

    LIFE SCIENCES   Vol. 263   page: 118577   2020.12

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  16. Gene Expression Profile at the Motor Endplate of the Neuromuscular Junction of Fast-Twitch Muscle Reviewed

    Huang, K; Li, J; Ito, M; Takeda, JI; Ohkawara, B; Ogi, T; Masuda, A; Ohno, K

    FRONTIERS IN MOLECULAR NEUROSCIENCE   Vol. 13   page: 154   2020.9

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  17. CTGF/CCN2 facilitates LRP4-mediated formation of the embryonic neuromuscular junction Reviewed

    Ohkawara, B; Kobayakawa, A; Kanbara, S; Hattori, T; Kubota, S; Ito, M; Masuda, A; Takigawa, M; Lyons, KM; Ishiguro, N; Ohno, K

    EMBO REPORTS   Vol. 21 ( 8 ) page: e48462   2020.8

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  18. Zonisamide ameliorates progression of cervical spondylotic myelopathy in a rat model Reviewed

    Kanbara, S; Ohkawara, B; Nakashima, H; Ohta, K; Koshimizu, H; Inoue, T; Tomita, H; Ito, M; Masuda, A; Ishiguro, N; Imagama, S; Ohno, K

    SCIENTIFIC REPORTS   Vol. 10 ( 1 ) page: 13138   2020.8

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  19. tRIP-seq reveals repression of premature polyadenylation by co-transcriptional FUS-U1 snRNP assembly Reviewed

    Masuda, A; Kawachi, T; Takeda, J; Ohkawara, B; Ito, M; Ohno, K

    EMBO REPORTS   Vol. 21 ( 5 ) page: e49890   2020.5

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.15252/embr.201949890

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  20. SRSF3 and hnRNP K Antagonistically Regulate Splicing of Large Exons

    Kawachi, T; Masuda, A; Takeda, J; Ito, M; Hamaguchi, T; Ohno, K

    FASEB JOURNAL   Vol. 34   2020.4

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  21. Ubiquitination of DNA Damage-Stalled RNAPII Promotes Transcription-Coupled Repair Reviewed

    Nakazawa, Y; Hara, Y; Oka, Y; Komine, O; van den Heuvel, D; Guo, CW; Daigaku, Y; Isono, M; He, YX; Shimada, M; Kato, K; Jia, N; Hashimoto, S; Kotani, Y; Miyoshi, Y; Tanaka, M; Sobue, A; Mitsutake, N; Suganami, T; Masuda, A; Ohno, K; Nakada, S; Mashimo, T; Yamanaka, K; Luijsterburg, MS; Ogi, T

    CELL   Vol. 180 ( 6 ) page: 1228 - +   2020.3

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  22. Author Correction: Mianserin suppresses R-spondin 2-induced activation of Wnt/β-catenin signaling in chondrocytes and prevents cartilage degradation in a rat model of osteoarthritis.

    Okura T, Ohkawara B, Takegami Y, Ito M, Masuda A, Seki T, Ishiguro N, Ohno K

    Scientific reports   Vol. 10 ( 1 ) page: 2995   2020.2

  23. Inhibition of cyclooxygenase-1 by nonsteroidal anti-inflammatory drugs demethylates MeR2 enhancer and promotes <i>Mbnl1</i> transcription in myogenic cells

    Huang, K; Masuda, A; Chen, GY; Bushra, S; Kamon, M; Araki, T; Kinoshita, M; Ohkawara, B; Ito, M; Ohno, K

    SCIENTIFIC REPORTS   Vol. 10 ( 1 ) page: 2558   2020.2

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  24. Mianserin suppresses R-spondin 2-induced activation of Wnt/β-catenin signaling in chondrocytes and prevents cartilage degradation in a rat model of osteoarthritis

    Okura, T; Ohkawara, B; Takegami, Y; Ito, M; Masuda, A; Seki, T; Ishiguro, N; Ohno, K

    SCIENTIFIC REPORTS   Vol. 9 ( 1 ) page: 2808   2019.2

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  25. Differential effects of spinal motor neuron-derived and skeletal muscle-derived Rspo2 on acetylcholine receptor clustering at the neuromuscular junction

    Li Jin, Ito Mikako, Ohkawara Bisei, Masuda Akio, Ohno Kinji

    SCIENTIFIC REPORTS   Vol. 8 ( 1 ) page: 13577   2018.9

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/s41598-018-31949-7

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  26. Lack of Fgf18 causes abnormal clustering of motor nerve terminals at the neuromuscular junction with reduced acetylcholine receptor clusters

    Ito Kenyu, Ohkawara Bisei, Yagi Hideki, Nakashima Hiroaki, Tsushima Mikito, Ota Kyotaro, Konishi Hiroyuki, Masuda Akio, Imagama Shiro, Kiyama Hiroshi, Ishiguro Naoki, Ohno Kinji

    SCIENTIFIC REPORTS   Vol. 8 ( 1 ) page: 434   2018.1

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/s41598-017-18753-5

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  27. MYRF Is Associated with Encephalopathy with Reversible Myelin Vacuolization

    Kurahashi Hirokazu, Azuma Yoshiteru, Masuda Akio, Okuno Tatsuya, Nakahara Eri, Imamura Takuji, Saitoh Makiko, Mizuguchi Masashi, Shimizu Toshiaki, Ohno Kinji, Okumura Akihisa

    ANNALS OF NEUROLOGY   Vol. 83 ( 1 ) page: 98 - 106   2018.1

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/ana.25125

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  28. Rules and tools to predict the splicing effects of exonic and intronic mutations

    Ohno Kinji, Takeda Jun-ichi, Masuda Akio

    WILEY INTERDISCIPLINARY REVIEWS-RNA   Vol. 9 ( 1 )   2018.1

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/wrna.1451

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  29. Fluoxetine ameliorates cartilage degradation in osteoarthritis by inhibiting Wnt/beta-catenin signaling

    Miyamoto Kentaro, Ohkawara Bisei, Ito Mikako, Masuda Akio, Hirakawa Akihiro, Sakai Tadahiro, Hiraiwa Hideki, Hamada Takashi, Ishiguro Naoki, Ohno Kinji

    PLOS ONE   Vol. 12 ( 9 ) page: e0184388   2017.9

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    DOI: 10.1371/journal.pone.0184388

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  30. SRSF1 suppresses selection of intron-distal 5 ' splice site of DOK7 intron 4 to generate functional full-length Dok-7 protein

    Bin Ahsan Khalid, Masuda Akio, Rahman Mohammad Alinoor, Takeda Jun-ichi, Nazim Mohammad, Ohkawara Bisei, Ito Mikako, Ohno Kinji

    SCIENTIFIC REPORTS   Vol. 7 ( 1 ) page: 10446   2017.9

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/s41598-017-11036-z

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  31. Splicing regulation of the human acetylcholinesterase gene

    Ohno Kinji, Nazim Mohammad, Masuda Akio

    JOURNAL OF NEUROCHEMISTRY   Vol. 142   page: 198 - 198   2017.8

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  32. Splicing regulation and dysregulation of cholinergic expressed at the neuromuscular junction

    Ohno Kinji, Rahman Mohammad Alinoor, Nazim Mohammad, Nasrin Farhana, Lin Yingni, Takeda Jun-ichi, Masuda Akio

    JOURNAL OF NEUROCHEMISTRY   Vol. 142   page: 64 - 72   2017.8

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/jnc.13954

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  33. Wnt/beta-catenin signaling suppresses expressions of Scx, Mkx, and Tnmd in tendon-derived cells

    Kishimoto Yasuzumi, Ohkawara Bisei, Sakai Tadahiro, Ito Mikako, Masuda Akio, Ishiguro Naoki, Shukunami Chisa, Docheva Denitsa, Ohno Kinji

    PLOS ONE   Vol. 12 ( 7 ) page: e0182051   2017.7

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    DOI: 10.1371/journal.pone.0182051

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  34. Six GU-rich (6GU(R)) FUS-binding motifs detected by normalization of CLIP-seq by Nascent-seq

    Takeda Jun-Ichi, Masuda Akio, Ohno Kinji

    GENE   Vol. 618   page: 57 - 64   2017.6

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    DOI: 10.1016/j.gene.2017.04.008

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  35. Competitive regulation of alternative splicing and alternative polyadenylation by hnRNP H and CstF64 determines acetylcholinesterase isoforms

    Nazim Mohammad, Masuda Akio, Rahman Mohammad Alinoor, Nasrin Farhana, Takeda Jun-Ichi, Ohe Kenji, Ohkawara Bisei, Ito Mikako, Ohno Kinji

    NUCLEIC ACIDS RESEARCH   Vol. 45 ( 3 ) page: 1455 - 1468   2017.2

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1093/nar/gkw823

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  36. Splicing regulation and dysregulation of cholinergic genes expressed at the neuromuscular junction Invited Reviewed

    Ohno K, Rahman MA, Nazim M, Nasrin F, Lin Y, Takeda J, Masuda A

    J Neurochem   Vol. 142   page: 64-72   2017

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  37. FUS-mediated regulation of alternative RNA processing in neurons: insights from global transcriptome analysis. Reviewed

    Masuda A, Takeda J, Ohno K

    Wiley interdisciplinary reviews. RNA   Vol. 7 ( 3 ) page: 330-40   2016.5

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    DOI: 10.1002/wrna.1338

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  38. Tranilast stimulates endochondral ossification by upregulating SOX9 and RUNX2 promoters. Reviewed

    Hasegawa S, Kitoh H, Ohkawara B, Mishima K, Matsushita M, Masuda A, Ishiguro N, Ohno K

    Biochemical and biophysical research communications   Vol. 470 ( 2 ) page: 356-61   2016.2

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    DOI: 10.1016/j.bbrc.2016.01.044

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  39. Arginine methylation of ubiquitin-associated protein 2-like is required for the accurate distribution of chromosomes. Reviewed

    Maeda M, Hasegawa H, Sugiyama M, Hyodo T, Ito S, Chen D, Asano E, Masuda A, Hasegawa Y, Hamaguchi M, Senga T

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology   Vol. 30 ( 1 ) page: 312-23   2016.1

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1096/fj.14-268987

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  40. Phenylbutazone induces expression of MBNL1 and suppresses formation of MBNL1-CUG RNA foci in a mouse model of myotonic dystrophy Reviewed

    Chen, G. Masuda, A. Konishi, H. Ohkawara, B. Ito, M. Kinoshita, M. Kiyama, H. Matsuura, T. Ohno, K.

    Sci Rep.   Vol. 6   page: 25317   2016

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  41. Lansoprazole Upregulates Polyubiquitination of the TNF Receptor-Associated Factor 6 and Facilitates Runx2-mediated Osteoblastogenesis. Reviewed

    Mishima K, Kitoh H, Ohkawara B, Okuno T, Ito M, Masuda A, Ishiguro N, Ohno K

    EBioMedicine   Vol. 2 ( 12 ) page: 2046-61   2015.11

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.ebiom.2015.11.024

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  42. Zonisamide Enhances Neurite Elongation of Primary Motor Neurons and Facilitates Peripheral Nerve Regeneration In Vitro and in a Mouse Model. Reviewed

    Yagi H, Ohkawara B, Nakashima H, Ito K, Tsushima M, Ishii H, Noto K, Ohta K, Masuda A, Imagama S, Ishiguro N, Ohno K

    PloS one   Vol. 10 ( 11 ) page: e0142786   2015.11

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    DOI: 10.1371/journal.pone.0142786

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  43. Collagen Q and anti-MuSK autoantibody competitively suppress agrin/LRP4/MuSK signaling. Reviewed

    Otsuka K, Ito M, Ohkawara B, Masuda A, Kawakami Y, Sahashi K, Nishida H, Mabuchi N, Takano A, Engel AG, Ohno K

    Scientific reports   Vol. 5   page: 13928   2015.9

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/srep13928

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  44. SRSF1 and hnRNP H antagonistically regulate splicing of COLQ exon 16 in a congenital myasthenic syndrome. Reviewed

    Rahman MA, Azuma Y, Nasrin F, Takeda J, Nazim M, Bin Ahsan K, Masuda A, Engel AG, Ohno K

    Scientific reports   Vol. 5   page: 13208   2015.8

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    DOI: 10.1038/srep13208

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  45. A missense mutation in domain III in HSPG2 in Schwartz-Jampel syndrome compromises secretion of perlecan into the extracellular space. Reviewed

    Iwata S, Ito M, Nakata T, Noguchi Y, Okuno T, Ohkawara B, Masuda A, Goto T, Adachi M, Osaka H, Nonaka R, Arikawa-Hirasawa E, Ohno K

    Neuromuscular disorders : NMD   Vol. 25 ( 8 ) page: 667-71   2015.8

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    DOI: 10.1016/j.nmd.2015.05.002

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  46. Meclozine Promotes Longitudinal Skeletal Growth in Transgenic Mice with Achondroplasia Carrying a Gain-of-Function Mutation in the FGFR3 Gene.

        2015.2

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    DOI: doi: 10.1210/en.2014-1914.

  47. Congenital myasthenic syndrome in Japan: Ethnically unique mutations in muscle nicotinic acetylcholine receptor subunits.

    Azuma Y, Nakata T, Tanaka M, Shen XM, Ito M, Iwata S, Okuno T, Nomura Y, Ando N, Ishigaki K, Ohkawara B, Masuda A, Natsume J, Kojima S, Sokabe M, Ohno K.

    Neuromuscul Disord.     2015.1

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    DOI: doi: 10.1016/j.nmd.2014.09.002.

  48. A missense mutation in domain III in HSPG2 in Schwartz-Jampel syndrome compromises secretion of perlecan into the extracellular space

    Iwata S, Ito M, Nakata T, Noguchi Y, Okuno T, Ohkawara B, Masuda A, Goto T, Adachi M, Osaka H, Nonaka R, Arikawa-Hirasawa E, Ohno K

    Neuromuscul Disord     page: 667-71   2015

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  49. Inhibition of SNW1 association with spliceosomal proteins promotes apoptosis in breast cancer cells Reviewed

    Sato N, Maeda M, Sugiyama M, Ito S, Hyodo T, Masuda A, Tsunoda N, Kokuryo T, Hamaguchi M, Nagino M, Senga T

    Cancer Med   Vol. 4 ( 2 ) page: 268-77   2015

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  50. HnRNP C, YB-1 and hnRNP L coordinately enhance skipping of human MUSK exon 10 to generate a Wnt-insensitive MuSK isoform.

    Nasrin F, Rahman MA, Masuda A, Ohe K, Takeda J, Ohno K.

    Sci Rep.     2014.10

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    DOI: doi: 10.1038/srep06841.

  51. LRP4 induces extracellular matrix productions and facilitates chondrocyte differentiation.

    Asai N, Ohkawara B, Ito M, Masuda A, Ishiguro N, Ohno K.

    Biochem Biophys Res Commun.     2014.8

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    DOI: doi: 10.1371/journal.pone.0092699

  52. LRP4 third β-propeller domain mutations cause novel congenital myasthenia by compromising agrin-mediated musk signaling in a position-specific manner Reviewed

    Ohkawara, B. and Cabrera-Serrano, M. and Nakata, T. and Milone, M. and Asai, N. and Ito, K. and Ito, M. and Masuda, A. and Ito, Y. and Engel, A. G. and Ohno, K.

    Hum Mol Genet     page: in press   2014

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  53. Verapamil protects against cartilage degradation in osteoarthritis by inhibiting Wnt/β-catenin signaling Reviewed

    Takamatsu, A. and Ohkawara, B. and Ito, M. and Masuda, A. and Sakai, T. and Ishiguro, N. and Ohno, K.

    PLOS ONE     page: in press   2014

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  54. FUS-regulated region- and cell-type-specific transcriptome is associated with cell selectivity in ALS/FTLD Reviewed

    Fujioka, Y. and Ishigaki, S. and Masuda, A. and Iguchi, Y. and Udagawa, T. and Watanabe, H. and Katsuno, M. and Ohno, K. and Sobue, G.

    Sci Rep   Vol. 3   page: 2388   2013

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  55. Meclozine facilitates proliferation and differentiation of chondrocytes by attenuating abnormally activated FGFR3 signaling in achondroplasia Reviewed

    Matsushita, M. and Kitoh, H. and Ohkawara, B. and Mishima, K. and Kaneko, H. and Ito, M. and Masuda, A. and Ishiguro, N. and Ohno, K.

    PLoS ONE   Vol. 8 ( 12 ) page: e81569   2013

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  56. Mutations in the C-Terminal Domain of ColQ in Endplate Acetylcholinesterase Deficiency Compromise ColQ-MuSK Interaction Reviewed

    Nakata, T. and Ito, M. and Azuma, Y. and Otsuka, K. and Noguchi, Y. and Komaki, H. and Okumura, A. and Shiraishi, K. and Masuda, A. and Natsume, J. and Kojima, S. and Ohno, K.

    Hum Mutat   Vol. 34 ( 7 ) page: 997-1004   2013

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  57. HnRNP L and hnRNP LL antagonistically modulate PTB-mediated splicing suppression of CHRNA1 pre-mRNA Reviewed

    Rahman, M. A. and Masuda, A. and Ohe, K. and Ito, M. and Hutchinson, D. O. and Mayeda, A. and Engel, A. G. and Ohno, K.

    Sci Rep   Vol. 3   page: 2931   2013

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  58. Clinically applicable antianginal agents suppress osteoblastic transformation of myogenic cells and heterotopic ossifications in mice Reviewed

    Yamamoto, R. and Matsushita, M. and Kitoh, H. and Masuda, A. and Ito, M. and Katagiri, T. and Kawai, T. and Ishiguro, N. and Ohno, K.

    J Bone Miner Metab   Vol. 31 ( 1 ) page: 26-33   2013

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  59. The ALS/FTLD-related RNA-binding proteins TDP-43 and FUS have common downstream RNA targets in cortical neurons Reviewed

    Honda, D. and Ishigaki, S. and Iguchi, Y. and Fujioka, Y. and Udagawa, T. and Masuda, A. and Ohno, K. and Katsuno, M. and Sobue, G.

    FEBS Open Bio   Vol. 4   page: 1-10   2013

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  60. Four parameters increase the sensitivity and specificity of the exon array analysis and disclose 25 novel aberrantly spliced exons in myotonic dystrophy Reviewed

    Yamashita, Y. and Matsuura, T. and Shinmi, J. and Amakusa, Y. and Masuda, A. and Ito, M. and Kinoshita, M. and Furuya, H. and Abe, K. and Ibi, T. and Sahashi, K. and Ohno, K.

    J Hum Genet   Vol. 57 ( 6 ) page: 368-74   2012

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  61. Position-dependent FUS-RNA interactions regulate alternative splicing events and transcriptions Reviewed

    Ishigaki, S. and Masuda, A. and Fujioka, Y. and Iguchi, Y. and Katsuno, M. and Shibata, A. and Urano, F. and Sobue, G. and Ohno, K.

    Sci Rep   Vol. 2   page: 529   2012

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  62. CUGBP1 and MBNL1 preferentially bind to 3' UTRs and facilitate mRNA decay Reviewed

    Masuda, A. and Andersen, H. S. and Doktor, T. K. and Okamoto, T. and Ito, M. and Andresen, B. S. and Ohno, K.

    Sci Rep   Vol. 2   page: 209   2012

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  63. Protein-anchoring strategy for delivering acetylcholinesterase to the neuromuscular junction Reviewed

    Ito, M. and Suzuki, Y. and Okada, T. and Fukudome, T. and Yoshimura, T. and Masuda, A. and Takeda, S. and Krejci, E. and Ohno, K.

    Mol Ther   Vol. 20 ( 7 ) page: 1384-92   2012

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  64. AG-dependent 3'-splice sites are predisposed to aberrant splicing due to a mutation at the first nucleotide of an exon Reviewed

    Fu, Y. and Masuda, A. and Ito, M. and Shinmi, J. and Ohno, K.

    Nucleic Acids Res   Vol. 39 ( 10 ) page: 4396-404   2011

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  65. Hyperuricemia cosegregating with osteogenesis imperfecta is associated with a mutation in GPATCH8 Reviewed

    Kaneko, H. and Kitoh, H. and Matsuura, T. and Masuda, A. and Ito, M. and Mottes, M. and Rauch, F. and Ishiguro, N. and Ohno, K.

    Hum Genet   Vol. 130 ( 5 ) page: 671-83   2011

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  66. Anti-MuSK autoantibodies block binding of collagen Q to MuSK Reviewed

    Kawakami, Y. and Ito, M. and Hirayama, M. and Sahashi, K. and Ohkawara, B. and Masuda, A. and Nishida, H. and Mabuchi, N. and Engel, A. G. and Ohno, K.

    Neurology   Vol. 77 ( 20 ) page: 1819-26   2011

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  67. Molecular hydrogen is protective against 6-hydroxydopamine-induced nigrostriatal degeneration in a rat model of Parkinson's disease Reviewed

    Fu, Y. and Ito, M. and Fujita, Y. and Ito, M. and Ichihara, M. and Masuda, A. and Suzuki, Y. and Maesawa, S. and Kajita, Y. and Hirayama, M. and Ohsawa, I. and Ohta, S. and Ohno, K.

    Neuroscience Letters   Vol. 453   page: 81–85   2009

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  68. Tannic acid facilitates expression of the polypyrimidine tract binding protein and alleviates deleterious inclusion of CHRNA1 exon P3A due to an hnRNP H-disrupting mutation in congenital myasthenic syndrome Reviewed

    Bian, Y. and Masuda, A. and Matsuura, T. and Ito, M. and Okushin, K. and Engel, A. G. and Ohno, K.

    Hum Mol Genet   Vol. 18 ( 7 ) page: 1229-37   2009

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  69. プロトタイプシナプスとしての神経筋接合部の病態と治療戦略

    大野欽司、伊藤美佳子、増田章男

    日本神経精神薬理学雑誌   Vol. 29 ( 4 ) page: 145-151   2009

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  70. Molecular hydrogen suppresses FcepsilonRI-mediated signal transduction and prevents degranulation of mast cells Reviewed

    Itoh, T. and Fujita, Y. and Ito, M. and Masuda, A. and Ohno, K. and Ichihara, M. and Kojima, T. and Nozawa, Y. and Ito, M.

    Biochem Biophys Res Commun   Vol. 389 ( 4 ) page: 651-6   2009

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  71. hnRNP H enhances skipping of a nonfunctional exon P3A in CHRNA1 and a mutation disrupting its binding causes congenital myasthenic syndrome Reviewed

    Masuda, A. and Shen, X. M. and Ito, M. and Matsuura, T. and Engel, A. G. and Ohno, K.

    Hum Mol Genet   Vol. 17 ( 24 ) page: 4022-4035   2008

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  72. Human branch point consensus sequence is yUnAy Reviewed

    Gao, K. and Masuda, A. and Matsuura, T. and Ohno, K.

    Nucleic Acids Res   Vol. 36 ( 7 ) page: 2257-2267   2008

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  73. Viral vector-medicated expression of human collagen Q in cultured cells Reviewed

    Ito, M. and Masuda, A. and Jinno, S. and Katagiri, T. and Krejci, E. and Ohno, K.

    Chem Biol Interact   Vol. 175 ( 1-3 ) page: 346-348   2008

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  74. In vitro and in silico analysis reveals an efficient algorithm to predict the splicing consequences of mutations at the 5' splice sites Reviewed

    Sahashi, K. and Masuda, A. and Matsuura, T. and Shinmi, J. and Zhang, Z. and Takeshima, Y. and Matsuo, M. and Sobue, G. and Ohno, K.

    Nucleic Acids Res   Vol. 35 ( 18 ) page: 5995-6003   2007

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  75. Ceramide inhibits LPS-induced production of IL-5, IL-10, and IL-13 from mast cells Reviewed

    Chiba, N. and Masuda, A. and Yoshikai, Y. and Matsuguchi, T.

    J Cell Physiol   Vol. 213 ( 1 ) page: 126-36   2007

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  76. Thermodynamic instability of siRNA duplex is a prerequisite for dependable prediction of siRNA activities Reviewed

    Ichihara, M. and Murakumo, Y. and Masuda, A. and Matsuura, T. and Asai, N. and Jijiwa, M. and Ishida, M. and Shinmi, J. and Yatsuya, H. and Qiao, S. and Takahashi, M. and Ohno, K.

    Nucleic Acids Res   Vol. 35 ( 18 ) page: e123   2007

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  77. Essential role of GATA transcriptional factors in the activation of mast cells Reviewed

    Masuda, A. and Hashimoto, K. and Yokoi, T. and Doi, T. and Kodama, T. and Kume, H. and Ohno, K. and Matsuguchi, T.

    J Immunol   Vol. 178 ( 1 ) page: 360-368   2007

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  78. Interleukin-15 induces IL-12 receptor beta1 gene expression through PU.1 and IRF 3 by targeting chromatin remodeling Reviewed

    Musikacharoen, T. and Oguma, A. and Yoshikai, Y. and Chiba, N. and Masuda, A. and Matsuguchi, T.

    Blood   Vol. 105 ( 2 ) page: 711-720   2005

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  79. A serine/threonine kinase, Cot/Tpl2, modulates bacterial DNA-induced IL-12 production and Th cell differentiation Reviewed

    Sugimoto, K. and Ohata, M. and Miyoshi, J. and Ishizaki, H. and Tsuboi, N. and Masuda, A. and Yoshikai, Y. and Takamoto, M. and Sugane, K. and Matsuo, S. and Shimada, Y. and Matsuguchi, T.

    J Clin Invest   Vol. 114 ( 6 ) page: 857-866   2004

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  80. Kupffer cell-derived interleukin 10 is responsible for impaired bacterial clearance in bile duct-ligated mice Reviewed

    Abe, T. and Arai, T. and Ogawa, A. and Hiromatsu, T. and Masuda, A. and Matsuguchi, T. and Nimura, Y. and Yoshikai, Y.

    Hepatology   Vol. 40 ( 2 ) page: 414-423   2004

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  81. The interaction between GATA proteins and activator protein-1 promotes the transcription of IL-13 in mast cells Reviewed

    Masuda, A. and Yoshikai, Y. and Kume, H. and Matsuguchi, T.

    J Immunol   Vol. 173 ( 9 ) page: 5564-5573   2004

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  82. LPS刺激によるマスト細胞からのサイトカイン産生機構におけるセラミドの役割

    千葉紀香、増田章男、松口徹也

    アレルギー科   Vol. 15 ( 3 ) page: 220-227   2003

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  83. JNK-interacting protein 3 associates with Toll-like receptor 4 and is involved in LPS-mediated JNK activation Reviewed

    Matsuguchi, T. and Masuda, A. and Sugimoto, K. and Nagai, Y. and Yoshikai, Y.

    Embo J   Vol. 22 ( 17 ) page: 4455-4464   2003

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  84. Toll like receptorを介するマスト細胞の活性化

    増田章男、松口徹也

    臨床免疫   Vol. 39 ( 6 ) page: 633-637   2003

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  85. Th2 cytokine production from mast cells is directly induced by lipopolysaccharide and distinctly regulated by c-Jun N-terminal kinase and p38 pathways Reviewed

    Masuda, A. and Yoshikai, Y. and Aiba, K. and Matsuguchi, T.

    J Immunol   Vol. 169 ( 7 ) page: 3801-3810   2002

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  86. Interleukin-15 prevents mouse mast cell apoptosis through STAT6-mediated Bcl-xL expression Reviewed

    Masuda, A. and Matsuguchi, T. and Yamaki, K. and Hayakawa, T. and Yoshikai, Y.

    J Biol Chem   Vol. 276 ( 28 ) page: 26107-26113   2001

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  87. Cutting edge: naturally occurring soluble form of mouse Toll-like receptor 4 inhibits lipopolysaccharide signaling Reviewed

    Iwami, K. I. and Matsuguchi, T. and Masuda, A. and Kikuchi, T. and Musikacharoen, T. and Yoshikai, Y.

    J Immunol   Vol. 165 ( 12 ) page: 6682-6686   2000

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  88. Interleukin-15 induces rapid tyrosine phosphorylation of STAT6 and the expression of interleukin-4 in mouse mast cells Reviewed

    Masuda, A. and Matsuguchi, T. and Yamaki, K. and Hayakawa, T. and Kubo, M. and LaRochelle, W. J. and Yoshikai, Y.

    J Biol Chem   Vol. 275 ( 38 ) page: 29331-29337   2000

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Books 6

  1. Detection of RNA-protein interaction sites by tRIP-seq

    ( Role: Sole author)

    2022.11 

  2. Liquid-liquid phase separation of transcription factors are sustained by large exons in vertebrates

    ( Role: Sole author)

    2022.10 

  3. Detection of RNA modification in low input samples by tRIP-seq

    ( Role: Sole author)

    2021.12 

  4. Regulation of mRNA length by FUS

    Masuda A and Ohno K( Role: Sole author)

    2016.4 

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    Language:Japanese

  5. Neurodegeneration-associated RNA-binding protein, FUS, regulates mRNA length

    Masuda A and Ohno K( Role: Sole author)

    ATLAS of Science  2016.2 

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    Language:Japanese

  6. Activation of mast cells through toll like receptors

    Akio Masuda, Tetsuya Matsuguchi( Role: Joint author)

    2003.6 

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    Language:Japanese Book type:Scholarly book

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Presentations 18

  1. Spatial organization of RNA-binding protein networks to regulate splicing

    2023.7.5 

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    Event date: 2023.7

    Language:English   Presentation type:Oral presentation (general)  

  2. RNA結合タンパクMatrin3が形成する核内顆粒による遺伝子発現制御 Invited

    増田章男、岡本喬明、大野欽司

    第7回日本筋学会学術集会  2021.12.11 

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    Event date: 2021.12

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

    Venue:京都  

  3. Identification of the nuclear speckles enriched with MATR3, which functionally regulate alternative splicing through spatial compartmentalization by LLPS

    Takaaki Okamoto, Akio Masuda, Kinji Ohno

    2021.12.3 

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    Event date: 2021.12 - 2121.12

    Language:English   Presentation type:Symposium, workshop panel (public)  

  4. The splicing mechanism that secures large exons encoding intrinsic disordered regions of transcription factors

    Akio Masuda, Toshihiko Kawachi, Kinji Ohno

    The 43st Annual Meeting of the Molecular Biology Society of Japan  2020.12 

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    Event date: 2020.12

    Language:English   Presentation type:Symposium, workshop panel (nominated)  

    Venue:On line   Country:Japan  

  5. The splicing mechanism that secures large exons encoding intrinsic disordered regions of transcription factors International conference

    Toshihiko Kawachi Akio Masuda, Jun-ichi Takeda, Mikako Ito, Tomonari Hamaguchi, Kinji Ohno

    Experimental Biology 2020 Meeting  2020.4  Federation of American Societies for Experimental Biology

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    Event date: 2020.4

    Language:English   Presentation type:Poster presentation  

    Venue:On line   Country:United States  

  6. Identification of U1 snRNP-FUS-RNA interactome co-transcriptionally assembled on RNA polymerase II by targeted RNA immunoprecipitation (tRIP

    Akio Masuda, Toshihiko Kawachi, Jun-ichi Takeda, Kinji Ohno

    The 42st Annual Meeting of the Molecular Biology Society of Japan  2019.12 

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    Event date: 2019.12

    Language:English   Presentation type:Symposium, workshop panel (public)  

    Venue:Fukuoka   Country:Japan  

  7. The interaction between SRSF3 and hnRNP K regulates the splicing of internal large exons

    Akio Masuda, Toshihiko Kawachi, Yoshihiro Yamachita, Kinji Ohno

    The 21st RNA Meeting  2019.7 

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    Event date: 2019.7

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:Tokyo   Country:Japan  

  8. Targeted RNA immunoprecipitation (tRIP) identified FUS-U1 snRNP interaction on nascent RNA as a regulator of mRNA length

    Akio Masuda, Toshihiko Kawachi, Jun-ichi Takeda, Kinji Ohno

    The 41st Annual Meeting of the Molecular Biology Society of Japan  2018.11 

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    Event date: 2018.11

    Language:English   Presentation type:Poster presentation  

    Venue:Yokohama   Country:Japan  

  9. Efficient identification of protein-protein-RNA tertiary interaction in living cells International conference

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    Event date: 2017.7

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  10. Binding of FUS to promoter upstream transcripts, PROMPTs, globally regulates gene transcription International conference

    Akio Masuda, Jun-ichi Takeda, Takaaki Okamoto, Kinji Ohno

    The annual meeting of the RNA society 

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    Event date: 2016

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  11. Position-specific binding of FUS regulates mRNA length

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    Event date: 2015.7

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  12. Position-specific binding of FUS to nascent RNA regulates alternative polyadenylation

    Akio Masuda, Junichi Takeda, Tatsuya Okuno, Kinji Ohno

    The 37th Annual Meeting of the Molecular Biology Society of Japan  

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    Event date: 2014.11

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  13. FUS regulates transcription termination through binding to nascent RNA International conference

    Masuda A, Okuno T, Okamoto T, Ohno K

    43rd Annual Meeting, Society for Neuroscience  

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    Event date: 2013.11

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  14. Global analysis reveals relationship between RNA-binding sites of FUS and transcriptional regulation International conference

    Masuda A, Okuno T, Okamoto T, Ohno K

    8th Brain Research Conference 

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    Event date: 2013.11

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  15. Global mapping of FUS-binding sites and global profiling of FUS-mediated RNA metabolisms in the mouse brain International conference

    Masuda A, Ishigaki S, Fujioka Y, Iguchi Y, Katsuno M, Shibata A, Urano F, Sobue G, Ohno K

    62nd Annual Meeting of the American Society of Human Genetics 

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    Event date: 2012.11

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  16. Global analysis of RNA-binding sites of CUGBP1 and MBNL1 reveal their preferential binding to 3' UTRs to regulate mRNA stability International conference

    Masuda A, Andersen HS, Doktor TK, Okamoto T, Ito I, Andresen BS, Ohno K

    The 11th Annual Scientific Meeting of the Asian and Oceanian Myology Center 

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    Event date: 2012.6

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  17. Genome-wide analysis of RNA-binding sites of HuR International conference

    Masuda A, Ito M, Fujita Y, Ohno K

    16th Annual Meeting of the RNA Society 

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    Event date: 2011.6

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  18. マスト細胞に発現するTLRシグナル伝達

    松口徹也 増田章男

    第15回日本アレルギー学会 春季臨床大会 シンポジウム2 

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    Event date: 2003

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

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Research Project for Joint Research, Competitive Funding, etc. 9

  1. 液-液相分離を正常化する核酸医薬によるFTLD治療法開発

    Grant number:22ek0109497s0402  2021.4 - 2024.3

    国立研究開発法人日本医療研究開発機構  難治性疾患実用化研究事業 

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    Grant type:Competitive

  2. 神経疾患関連RNA結合タンパクFUSによる動的クロマチン制御

    2017.4 - 2018.3

    堀科学芸術振興財団 研究助成 

    増田章男

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    Grant type:Competitive

    神経疾患関連RNA結合タンパクFUSによる動的クロマチン制御

  3. 神経筋接合部特異的RNA代謝機構の解明

    2016 - 2018

    内藤記念科学奨励金・研究助成  

    増田章男

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    Grant type:Competitive

  4. Aberrant splicing in neuromuscular diseases(大野欽司)

    2009 - 2013.3

  5. マスト細胞における、転写因子GATAの役割

    2003

    (財)共済団医学奨励助成 H15 

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    Grant type:Competitive

  6. LPSによる気道アレルギー性炎症増悪における、マスト細胞の役割

    2003

    (財)花王芸術・科学財団 平成16年度科学技術研究助成 

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    Grant type:Competitive

  7. The role of ceramide in mast cell functions

    2003

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    Grant type:Competitive

  8. マスト細胞におけるIL-13産生機構の解析

    2002

    名古屋大学学術振興基金 H14年度学術研究助成 

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    Grant type:Competitive

  9. マスト細胞におけるTH2サイトカイン産生機構の解析

    2002

    (財)日本アレルギー協会 北陸製薬 アレルギー学術奨励賞 

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    Grant type:Competitive

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KAKENHI (Grants-in-Aid for Scientific Research) 18

  1. Investigation of the molecular formations and the pathomechanisms of the neuromuscular junction

    Grant number:23H02794  2023.4 - 2026.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Authorship:Coinvestigator(s) 

  2. in situ cDNA増幅による超高感度 RNA-蛋白 相互作用 解析法の開発

    Grant number:22K19269  2022.6 - 2024.3

    科学研究費助成事業  挑戦的研究(萌芽)

    増田 章男

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    Authorship:Principal investigator 

    Grant amount:\6500000 ( Direct Cost: \5000000 、 Indirect Cost:\1500000 )

    転写・翻訳の根幹を成すRNA代謝の中でも、特に重要視されているRNA結合蛋白-RNAの相互作用に対し、画期的な高感度・高効率解析技術の開発を目指す。申請者は、すでに現在の標準解析技術CLIPの100倍以上の感度でRNA-タンパク相互作用/RNA修飾を検出するtRIP-seqを開発したが、まだ不十分であった。本研究課題では、tRIP法をさらに改変することで、超高感度RNA-タンパク相互作用検出法を開発し、次世代のRNA分子動態研究に向けた飛躍を狙う。
    研究代表者が開発した効率的RNA-タンパク相互作用検出法 (tRIP法) をベースに、各実験ステップの改変を行うことで、さらなる効率化法を探索した。
    i) マルチプレックス化への検討。random primer部位とindex部位を持つoligo DNAをconjugationしたRBP特異抗体を使用したマルチプレックス化の適正条件について検討した。Conjugation時の至適抗体/DNA量や結合反応条件の検討を行い、効率的なconjugationに成功した。さらに、得られた抗体を用いてRNA結合タンパクFUSに対するFUS-tRIP libraryの作製ができることを確認した。
    ii)固定法の改善: 細胞内RNA-タンパク相互作用の固定に、tRIP法ではUVクロスリンクを利用していたが、ホルムアルデヒドへの代替可能性を探索した。DNA-タンパク相互作用解析法であるChIP法では、生細胞に対し1%ホルムアルデヒドを用いて10分常温での固定が一般的である。我々は、ホルムアルデヒド濃度・反応温度・反応時間の検討を行い、RNA-タンパク相互作用の固定には、同様のバッファーで室温2分で十分なことを見出した。
    iii)細胞内クロマチン分画回収法の構築。スプライシングや3' end proceccing factor制御をはじめとするRNA代謝制御RNA結合タンパクのほとんどが細胞内クロマチン分画に分布している。しかし、クロマチン分画にはDNAおよび様々な核内タンパクが高密度に集積しており、そこから効率的に目的タンパクを回収することは、困難であった。我々は、今回、その改良に取り組み、抽出液の塩濃度を急激に変化させることでクロマチン分画が沈殿可能であり、その沈殿から効率的にRNAを回収する方法の確立に成功した。
    当初、UVクロスリンク法に変えて、ChIPで汎用されているホルムアルデヒドを用いたRNA-タンパク複合体のクロスリンクを行うことで、大幅な感度向上を目指していた。しかし、ホルムアルデヒドによるクロスリンク効率は、UVクロスリンクより圧倒的に高いものの、その後のRT-PCR反応を阻害してしまうことが判明した。このRT-PCR阻害を最小限に抑えるべく、時間や温度、バッファー条件など、様々な検討を行ったため、進捗状況に遅れが生じた。
    2022年度に達成した、i)oligo結合抗体によるtRIP解析、ii)RNA-タンパククロスリンク法の改善、iii)新規クロマチン分画回収法をもとに、これらの使用条件調節を行うことでRNA-タンパク解析法の高感度化を進めていく。

  3. 天然変性領域 (IDR) 形成を支えるスプライシング機構から俯瞰する相分離現象

    Grant number:21H02476  2021.4 - 2025.3

    科学研究費助成事業  基盤研究(B)

    増田 章男, 石垣 診祐

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    Grant amount:\17160000 ( Direct Cost: \13200000 、 Indirect Cost:\3960000 )

    蛋白内の天然変性領域(IDR) は、その限定されたアミノ酸組成が相分離(LLPS)を引き起こすことで、膜のない細胞内小分画や複合体の形成に中核的な役割を持つ。申請者は、複数のRNA結合蛋白(RBP)が、それぞれ異なるアミノ酸・塩基組成を持つIDRのスプライシングに必須で、異なる細胞内機能に関わることを見出している。本研究では、各RBPに支えられた異なる組成のIDRが、mRNA生合成からLLPSを介した細胞内機能に至るまで、一貫して異なっていることを明らかにし、それに基づいた系統別の細胞機能制御、および、それらの疾患病態での役割解明に挑む。
    IDR(天然変性領域)とRNA結合蛋白(RBP)の関係性を明らかにするため、生化学実験とBioinformatics解析の両面から探索を進めた。
    生化学実験で、人工天然変性領域の配列スクリーニング評価を行っていたところ、予期せぬことに、天然変性領域の相当割合が細胞内顆粒を形成せず、代わりに微細な網目状ネットワークを形成することが判明した。これまでのところ、天然変性領域を持つタンパクが細胞内で網目構造を持つことは、例外的な報告にとどまっており、その生理的意義は現在のところ全く解明されていない。その科学的重要性を考慮し、まず網目状ネットワークを精細に観察できる超解像度顕微鏡実験系の構築を行った。網目構造は、径100-400nmほどのポアサイズであり、超解像度顕微鏡の分解能限界に近い。このため、サンプルの固定法から染色・検出法に至るまで様々な条件検討を行い、十分な網目構造検出能を持つ解析系の構築に成功した。
    また、Bioinformatics解析で、annotation databaseから得られたヒト蛋白の全配列情報をもとに、IDRをコードするエクソンの分類を進めた。アミノ酸の組成/電荷/疎水性をもとに分類を行い、6種類のクラスターへの分別に成功し、RBPが特に集積しているクラスターを2つ発見した。
    これら2つのクラスターに属するRBPから数個ずつRBPを選択し、それらのリコンビナント蛋白を作製し、生化学的性質の違いを明らかにした。
    さらに、RT-PCRやtRIP解析、共免疫沈降実験などの生化学実験により、細胞内でのこれらクラスターRBP群の相互作用の検証を行い、スプライシングをはじめとするRNA代謝における生理的意義を検討した。
    当初、天然変性領域の蛋白が細胞内顆粒を形成する、との見込みで研究を行っていた。しかし想定に反し、人工天然変性領域の配列の相当割合が細胞内顆粒を形成せず、代わりに微細な網目状ネットワークを形成することが判明した。
    このため、網目状ネットワークを精細に観察できる実験系の新たな構築が必要となり、その実現に時間を割いたため、当初の計画よりも進捗が遅れ気味となった。
    網目状ネットワークを精細に観察できる超高解像度顕微鏡実験系の構築ができたため、今後、その定量解析方法の高精度化を検討する。各種RNA結合タンパクの抗体染色による核内RBP分布検出を様々なパラメーターを用いて解析できる統合的in silico画像定量ツールの構築を目指す。
    また、細胞・生化学実験を用いた正常RBPの細胞内機能解析をさらに進め、患者変異を導入したRBPの機能解析にも取り組んでいく。

  4. FTLDスペクトラムにおける核内RNP複合体の機能変化に基づく核酸医療の開発

    Grant number:21H02838  2021.4 - 2025.3

    科学研究費助成事業  基盤研究(B)

    石垣 診祐, 増田 章男, 藤岡 祐介

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    FTLDはタウオパチーである進行性核上性麻痺 (PSP)、大脳皮質基底核変性症 (CBD)と臨床・病理学的にスペクトラム形成することが知られている。申請者はFUS/SFPQ核内複合体の会合異常が、ALS/FTLDのみならず、PSP、CBDなど4R-tau優位のタウオパチーを含むFTLDスペクトラムに共通した病態変化であることを見出している。本研究はこの知見をを基盤にして、FTLDスペクトラムにおける神経細胞核内におけるFUS/SFPQ関連RNP複合体のprofile変化と、ターゲットのRNA動態の詳細を明らかにし、それをもとにした核酸医療薬を開発することが目的である。
    1)FTLDスペクトラム疾患におけるFUS/SFPQ関連RNP複合体profile変化の解明:これまでに神経細胞核内FUS/SFPQ複合体には家族性ALSの原因遺 伝子であるEWSR, MATR3など多くのRNPが含まれ、これらのALS関連RNA結合タンパク質もFUS、SFPQと同様にタウisoformを制御することを、剖検脳を用いた疾患横断的解析より、見出してきた。FUS/SFPQ関連RNP複合体の結合様式がFTLDスペクトラムでどのように変化しているか、剖検脳に加えて脊髄を用いた生化学的、免疫組織化学的解析からRNP profileを比較し、FUS、SFPQをはじめとしたRNPの変化が、脊髄の運動ニューロンレベルでも変化していることを明らかにした。FUSのin vitroにおける液液相分離の評価系を構築し、ALS関連変異体でphase separationに変化が起き、dropletを形成することを確認した。2)FTLDスペクトラムの病態基盤に共通のRNA代謝動態変化の解明:複合体に含まれるRNA結合タンパク質(RNP)の多くがタウisoformを制御するという知見は、FUS/SFPQ関連RNP複合体がタウ遺伝子MAPTを含む特定のRNA群に対して共通の様式を通じて制御を行っている可能性を示唆する。MAPTの選択的スプライシングに関与するRNPについて患者由来iPSC由来神経細胞を用いて、FUSとSFPQの微小局在の確認に着手した。 3)核酸医薬によるFTLDスペクトラム治療法の確立:上記までの病態メカニズム解析によって網羅的に同定したFUS/SFPQ関連RNP複合体のprofile(RNPの組み合わせ)変化、およびその標的RNA代謝変化をもとに、制御可能なoligonucleotideについてのスクリーニングに着手した。
    FUS/SFPQ関連RNP複合体の結合様式がFTLDスペクトラムでどのように変化しているかについて、免疫組織化学的解析を実施する上で必要な機器の故障のために遅延が生じている。このため、当初の研究計画で予定していた実験の一部が遅れ、年度内完了が困難となった。
    コロナ禍で未使用の学会旅費の物品費への流用と合わせて次年度に繰り越して遅延を回復することとした。

  5. Elucidation of molecular mechanisms of neuromuscular junction formations in physiology and pathology

    Grant number:20H03561  2020.4 - 2023.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    Ohno Kinji

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    Specific AIMs of the current project were to elucidate the physiological molecular structures of the neuromuscular junction (NMJ) and their aberrations in congenital myasthenic syndromes (CMS) to develop novel therapeutic modalities for CMS. We identified three novel secreted molecules (Rspo2, Fgf18, and Ctgf) and their cognate receptors (Lgr5, Fgfr2, Lrp4) that are essential for the formation and the maintenance of NMJ. We identified and functionally characterized mutations in the CHRND, CHRNG, and DOK7 genes in Japanese patients with CMS. In addition, we generated in vitro NMJ and found that anti-epileptic and anti-parkinsonian drug, zonisamide, induces the clustering of acetylcholine receptors by upregulating neuregulin. We also published an extensive review article on CMS by citing as many as 442 references.

  6. Analysis of the molecular basis of MERS-delirious behavior spectrum

    Grant number:18K07890  2018.4 - 2023.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Okumura Akihisa

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    A common missense mutation in the MYRF gene was identified by whole exome analysis in familial patients with recurrent mild encephalitis/ encephalopathy with reversible splenial lesion (MERS). Whole exome analysis was performed in other patients with MERS, and a novel missense MYRF gene mutation was identified in another patient with recurrent leukoencephalopathy.
    Variants in about 700 genes potentially regulated by MYRF have been analyzed in patients with repetitive and/or familial MERS and compared to controls without neurological disorders. In patients with MERS, variants in GFOD1, HEMK1, CDIP1, PCSK6, LGMN and SLC5A11 genes tended to be more common than in controls. No clear conclusions can be reached at present on the association between these gene variants and the development of MERS.

  7. Identification of the role of transcription termination and polyadenylation in ALS using multiple high-throughput sequencing analysis

    Grant number:18K06058  2018.4 - 2022.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Masuda Akio

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    Authorship:Principal investigator 

    Grant amount:\4420000 ( Direct Cost: \3400000 、 Indirect Cost:\1020000 )

    We developed the tRIP method (targeted RNA immunoprecipitation), which enables identification of the protein-RNA interaction sites to a similar level of accuracy as CLIP-seq, but requires only thousands of cells. tRIP requires only 2 days to generate a cDNA library with a single RNA purification step. tRIP adopts exonuclease treatment, and abrogates tedious SDS-PAGE and membrane transfer that are essential in CLIP methodology. High sensitivity of tRIP allows us to perform serial immunoprecipitation to identify the protein-protein-RNA interaction sites starting from a subnuclear fraction.tRIP provides new insights into the regulatory mechanism of co-transcriptional RNA processing by RNA processing factors.

  8. Identification of the role of transcription termination and polyadenylation in the pathogenesis of ALS using multiple high-throughput sequencing analyses

    Grant number:15K06755  2015.4 - 2019.3

    Masuda Akio

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    Grant amount:\5200000 ( Direct Cost: \4000000 、 Indirect Cost:\1200000 )

    RNA metabolism occurs in specific machineries of RNA, including RNA polymerase II (RNAP II), spliceosome, and 3’ end processing machinery. However, the transcriptome-wide detection of protein-RNA interactions in a subcellular component is challenging. Here, we developed the tRIP method (targeted RNA immunoprecipitation) to increase efficiency of RNA immunoprecipitation, which enables detection of UV-crosslinked protein-RNA interactions from thousands of cells. Application of tRIP to identification of protein-protein-RNA interactions revealed that FUS, a multifunctional RNA-binding protein associated with ALS, binds specifically upstream to alternative polyadenylation (APA) sites of nascent RNA engaged to RNAP II. Further tRIP analysis demonstrated that the FUS-U1 snRNP-RNA complex is the entity that suppresses APA.

  9. アルギニンのメチル化と翻訳による新たな細胞分裂制御機構の解析 研究課題

    Grant number:15K14505  2015.4 - 2017.3

    増田 章男

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    Authorship:Coinvestigator(s) 

  10. RNAスプライシングを介した新たな細胞分裂開始機構の解明

    Grant number:15K14505  2013.4 - 2015.3

    増田 章男

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    Authorship:Coinvestigator(s) 

  11. 神経筋接合部の正常構築と分子病態研究(大野欽司)

    2012.4 - 2015.3

    科学研究費補助金  基盤研究(B)

    大野欽司

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  12. 神経筋接合部特異的スプライシング機構の解明

    2012.4 - 2015.3

    科学研究費補助金  基盤研究(C)

    増田 章男

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    Authorship:Principal investigator 

  13. 神経筋接合分子欠損症におけるmRNA病態研究と治療法開発研究(大野欽司)

    2009.4 - 2012.3

    科学研究費補助金  基盤研究(B)

    大野欽司

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    Authorship:Coinvestigator(s) 

  14. 生活環境における吸入気体組成の調節に基づく健康維持と疾患制御の試み(市原正智)

    2008.4 - 2011.3

    科学研究費補助金  新学術領域研究 (研究課題提案型) 代表:市原正智  課題番号:20200021

    市原正智

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  15. アレルギー病態におけるRNA結合蛋白ROD1の役割

    2008.4 - 2011.3

    科学研究費補助金  基盤研究(C)

    増田 章男

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    Authorship:Principal investigator 

  16. 神経筋接合分子欠損症および他の筋疾患におけるmRNA病態研究と治療法開発研究(大野欽司)

    2007.4 - 2009.3

    科学研究費補助金  基盤研究(B)

    大野欽司

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    Authorship:Coinvestigator(s) 

  17. 先天性筋無力症候群に関与する神経筋接合部分子の分子病態研究(大野欽司)

    2005.4 - 2007.3

    科学研究費補助金  基盤研究(B)

    大野欽司

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  18. マスト細胞におけるIL-15レセプターの解析

    2002.4 - 2004.3

    科学研究費補助金  若手研究(B)

    増田章男

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Industrial property rights 1

  1. タンパク質−RNA相互作用の検出

    増田章男、大野欽司

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    Application no:特許願 2017-137406 号  Date applied:2017.8

    Country of applicant:Domestic  

 

Teaching Experience (On-campus) 16

  1. 生物学基礎

    2021

  2. 生物学基礎I

    2020

  3. CIBoGオミクス解析学

    2020

  4. 生物学基礎I

    2019

  5. 生体防御情報学特論

    2019

  6. 生物学基礎I

    2018

  7. 生物学基礎I

    2017

  8. 病因病態解析学特論

    2017

  9. 生物学基礎I

    2016

  10. 生物学基礎I

    2015

  11. 生物学基礎I

    2014

  12. 生物学基礎I

    2013

  13. 生物学基礎I

    2012

  14. 生物学基礎I

    2011

  15. 生物学基礎I

    2010

  16. 生物学基礎I

    2009

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Media Coverage 2

  1. 名古屋大医学部生のゲノム研究論文、著名学術誌に掲載 がんの病態解明の可能性 Newspaper, magazine

    東京新聞  東京新聞  https://www.tokyo-np.co.jp/article/141268  2021.11

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    Author:Other 

  2. ゲノム研究の名大医学生、がん解明の可能性 著名学術誌に論文 Newspaper, magazine

    中日新聞  中日新聞  中日新聞夕刊  2021.11

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    Author:Other