• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Hair bundle formation and tonotopy in genetic hearing loss models and the iPS cells

Research Project

Project/Area Number 18H02953
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 56050:Otorhinolaryngology-related
Research InstitutionJuntendo University

Principal Investigator

kamiya kazusaku  順天堂大学, 医学部, 准教授 (10374159)

Co-Investigator(Kenkyū-buntansha) 小池 卓二  電気通信大学, 大学院情報理工学研究科, 教授 (10282097)
安齋 崇  順天堂大学, 医学部, 助教 (20624852)
福永 一朗  順天堂大学, 大学院医学研究科, 非常勤助教 (20746581)
池田 勝久  順天堂大学, 医学部, 特任教授 (70159614)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2021: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2020: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords蝸牛器官培養 / 遺伝性難聴 / 人工多能性幹細胞 / 難聴マウス / 遺伝子難聴 / 聴覚 / 内耳有毛細胞 / 聴毛 / 周波数弁別 / iPS細胞
Outline of Final Research Achievements

Recently, abnormalities in frequency discrimination have been observed in some patients with abnormal sound perception, but the cause of these abnormalities is unknown and there are no objective diagnostic criteria. We reported the mice with abnormal frequency discrimination and confirmed the predicted abnormal propagation of basal menbrane vibration from basal (high frequency) to apical (low frequency) rotation. We further elucidated the possible causes of this abnormality by simulating the cochlear model and suggested the possiblity that high frequency hearing loss model abnormally recognize the sound as a low frequency sound. Furthermore, by developing a technology to generate cochlear cells from iPS cells, they were able to reproduce the pathophysiology of hearing loss and succeeded in generating hair cells using the same method, which is expected to lead to clinical applications of inner ear cell therapy in the future.

Academic Significance and Societal Importance of the Research Achievements

近年、周波数弁別の異常が散見されるがその原因は不明である。我々は遺伝子改変マウスの外有毛細胞の聴毛形成異常により、周波数弁別異常を持つ聴覚障害を発見した。同マウスは周波数弁別異常を持つ初めてのモデル動物であり、周波数弁別機構と聴覚神経系発達への影響を解明できる有用なモデルとなる。さらに我々はiPS細胞から蝸牛細胞を作製する技術開発により難聴病態を再現し、同様の方法で有毛細胞の作製を行った。周波数弁別異常マウスおよび同マウスiPS細胞由来有毛細胞を用いた生理学、分子生物学的解析により聴毛形成異常の機構や周波数弁別による聴覚神経系の適応発達の機構を解明しており、今後新しい内耳治療法が期待できる。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report

Research Products

(27 results)

All 2021 2020 2019 Other

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 6 results) Presentation (8 results) (of which Int'l Joint Research: 4 results,  Invited: 2 results) Book (2 results) Remarks (1 results) Patent(Industrial Property Rights) (6 results)

  • [Journal Article] Modeling Gap junction beta 2 gene-related deafness with human iPS2021

    • Author(s)
      Ichiro Fukunaga, Yoko Oe, Keiko Danzaki, Sayaka Ohta, Cheng Chen, Kyoko Shirai, Atsushi Kawano, Katsuhisa Ikeda, Kazusaku Kamiya
    • Journal Title

      Human molecular genetics

      Volume: 30 Pages: 1429-1442

    • DOI

      10.1093/hmg/ddab097

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Activin/Nodal/TGF-β Pathway Inhibitor Accelerates BMP4-Induced Cochlear Gap Junction Formation During in vitro Differentiation of Embryonic Stem Cells2021

    • Author(s)
      Ichiro Fukunaga, Yoko Oe, Cheng Chen, Keiko Danzaki, Sayaka Ohta, Akito Koike, Katsuhisa Ikeda, Kazusaku Kamiya
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 21 Pages: 1-12

    • DOI

      10.3389/fcell.2021.602197

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of two iPSC lines from siblings of a homozygous patient with hearing loss and a heterozygous carrier with normal hearing carrying p.G45E/Y136X mutation in GJB22021

    • Author(s)
      Fukunaga Ichiro、Oe Yoko、Danzaki Keiko、Ohta Sayaka、Chen Cheng、Iizumi Madoka、Shiga Takahiro、Matsuoka Rina、Anzai Takashi、Hibiya-Motegi Remi、Tajima Shori、Ikeda Katsuhisa、Akamatsu Wado、Kamiya Kazusaku
    • Journal Title

      Stem Cell Research

      Volume: 53 Pages: 102290-102290

    • DOI

      10.1016/j.scr.2021.102290

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Degradation and modification of cochlear gap junction proteins in the early development of age-related hearing loss.2020

    • Author(s)
      Tajima Shori、Danzaki Keiko、Ikeda Katsuhisa、Kamiya Kazusaku
    • Journal Title

      Experimental & Molecular Medicine

      Volume: 52 Pages: 166-175

    • DOI

      10.1038/s12276-020-0377-1

    • Related Report
      2020 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of two induced pluripotent stem cell lines from PBMCs of siblings carrying c.235delC mutation in the GJB2 gene associated with sensorineural hearing loss2020

    • Author(s)
      Fukunaga Ichiro、Shirai Kyoko、Oe Yoko、Danzaki Keiko、Ohta Sayaka、Shiga Takahiro、Chen Cheng、Ikeda Katsuhisa、Akamatsu Wado、Kawano Atsushi、Kamiya Kazusaku
    • Journal Title

      Stem Cell Research

      Volume: 47 Pages: 101910-101910

    • DOI

      10.1016/j.scr.2020.101910

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of the induced pluripotent stem cell (hiPSC) line (JUFMDOi004-A) from a patient with hearing loss carrying GJB2 (p.V37I) mutation2020

    • Author(s)
      Fukunaga Ichiro、Shiga Takahiro、Chen Cheng、Oe Yoko、Danzaki Keiko、Ohta Sayaka、Matsuoka Rina、Anzai Takashi、Hibiya-Motegi Remi、Tajima Shori、Ikeda Katsuhisa、Akamatsu Wado、Kamiya Kazusaku
    • Journal Title

      Stem Cell Research

      Volume: 43 Pages: 0-1

    • DOI

      10.1016/j.scr.2019.101674

    • Related Report
      2020 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Degradation and modification of cochlear gap junction proteins in the early development of age-related hearing loss.2020

    • Author(s)
      Tajima S, Danzaki K, Ikeda K, Kamiya K.
    • Journal Title

      Experimental and Molecular Medicine

      Volume: 52 Pages: 166-175

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of the induced pluripotent stem cell (hiPSC) line (JUFMDOi004-A) from a patient with hearing loss carrying GJB2 (p.V37I) mutation.2020

    • Author(s)
      Fukunaga I, Shiga T, Chen C, Oe Y, Danzaki K, Ohta S, Matsuoka R, Anzai T, Hibiya-Motegi R, Tajima S, Ikeda K, Akamatsu W, Kamiya K.
    • Journal Title

      Stem Cell Research

      Volume: 4

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of Functional CX26-Gap-Junction-Plaque-Forming Cells with Spontaneous Ca2+ Transients via a Gap Junction Characteristic of Developing Cochlea.2019

    • Author(s)
      Fukunaga I, Fujimoto A, Hatakeyama K, Kurebayashi N, Ikeda K, Kamiya K.
    • Journal Title

      Current Protocols in Stem Cell Biology

      Volume: 51

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of Functional CX26?Gap‐Junction‐Plaque‐Forming Cells with Spontaneous Ca 2+ Transients via a Gap Junction Characteristic of Developing Cochlea2019

    • Author(s)
      Fukunaga Ichiro、Fujimoto Ayumi、Hatakeyama Kaori、Kurebayashi Nagomi、Ikeda Katsuhisa、Kamiya Kazusaku
    • Journal Title

      Current Protocols in Stem Cell Biology

      Volume: 51

    • DOI

      10.1002/cpsc.100

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] 内耳上皮細胞を標的としたバイオ医薬品の開発2021

    • Author(s)
      神谷和作
    • Organizer
      第31回日本耳科学会総会・学術講演会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 内耳上皮細胞を標的としたバイオ医薬品の開発2021

    • Author(s)
      神谷和作
    • Organizer
      3.学会等名 2.発表標題 発明者 内耳上皮細胞を標的としたバイオ医薬品の開発 第31回日本耳科学会総会・学術講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 遺伝性難聴への遺伝子治療ベクターおよび中分子医薬品の開発2020

    • Author(s)
      神谷和作
    • Organizer
      第121回日本耳鼻咽喉科学会学術講演会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 内耳ギャップ結合遺伝子の加齢性難聴への関与2020

    • Author(s)
      神谷和作
    • Organizer
      第30回 日本耳科学会総会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Drug Screening and AAV Gene Therapy for GJB2 Related Hearing Loss with iPS cells2020

    • Author(s)
      Kazusaku Kamiya
    • Organizer
      ARO midwinter meeting 2019, San Jose, CA, USA
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Disease modelling and drug screening for GJB2 related hearing loss with iPS cells2020

    • Author(s)
      Kazusaku Kamiya
    • Organizer
      Inner Ear Biology 2019, Padua, Italy
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Drug Screening and AAV Gene Therapy for GJB2 Related Hearing Loss with iPS cells.2020

    • Author(s)
      Kazusaku Kamiya
    • Organizer
      ARO midwinter meeting 2019, San Jose, CA, USA
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Disease modelling and drug screening for GJB2 related hearing loss with iPS cells.2020

    • Author(s)
      Kazusaku Kamiya
    • Organizer
      Inner Ear Biology 2019, Padua, Italy
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Book] JOHNS耳鼻咽喉科・頭頸部外科【解説/特集】難聴を治す-2020年版 感音難聴と遺伝子治療2020

    • Author(s)
      神谷 和作
    • Publisher
      東京医学社
    • Related Report
      2019 Annual Research Report
  • [Book] 【解説/特集】難聴を治す-2020年版 感音難聴と遺伝子治療2020

    • Author(s)
      神谷 和作
    • Publisher
      JOHNS耳鼻咽喉科・頭頸部外科
    • Related Report
      2018 Annual Research Report
  • [Remarks] 患者iPS細胞で遺伝性難聴を再現 ~ 世界最多の難聴型への薬剤スクリーニングが可能に ~

    • URL

      https://med.juntendo.ac.jp/news/20210518-01.html

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Patent(Industrial Property Rights)] 改変型アデノ随伴ウイルスベクター2021

    • Inventor(s)
      神谷和作
    • Industrial Property Rights Holder
      順天堂大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report
  • [Patent(Industrial Property Rights)] 内耳前駆細胞の製造法2021

    • Inventor(s)
      神谷和作
    • Industrial Property Rights Holder
      順天堂大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report
  • [Patent(Industrial Property Rights)] 改変型アデノ随伴ウイルスベクター2021

    • Inventor(s)
      神谷和作
    • Industrial Property Rights Holder
      順天堂大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2020 Annual Research Report
  • [Patent(Industrial Property Rights)] 内耳前駆細胞の製造法2021

    • Inventor(s)
      神谷和作
    • Industrial Property Rights Holder
      順天堂大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2020 Annual Research Report
  • [Patent(Industrial Property Rights)] ギャップ結合機能制御剤のスクリーニング方法2019

    • Inventor(s)
      神谷 和作
    • Industrial Property Rights Holder
      学校法人順天堂大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-149966
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] ギャップ結合機能制御剤のスクリーニング方法2019

    • Inventor(s)
      神谷 和作
    • Industrial Property Rights Holder
      学校法人順天堂 大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-149966
    • Filing Date
      2019
    • Related Report
      2018 Annual Research Report

URL: 

Published: 2018-04-23   Modified: 2023-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi