橋本 寿之 (ハシモト ヒサユキ)

Hashimoto, Hisayuki

写真a

所属(所属キャンパス)

医学部 予防医療センター (信濃町)

職名

助教(有期)

外部リンク

その他の所属・職名 【 表示 / 非表示

  • 医学部, 循環器内科学教室, 助教

経歴 【 表示 / 非表示

  • 2006年04月
    -
    2008年03月

    栃木県済生会宇都宮病院 , 初期臨床研修医

  • 2008年04月
    -
    2009年03月

    慶應義塾大学病院 , 内科学教室, 専修医

  • 2009年04月
    -
    2011年03月

    慶應義塾大学, 医学部, グローバルCOEプログラム 研究員

  • 2011年04月
    -
    2012年03月

    慶應義塾大学, 大学院医学研究科, 助教

  • 2012年04月
    -
    2014年03月

    慶應義塾大学, 医学部 循環器内科学教室, 助教

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学歴 【 表示 / 非表示

  • 2000年04月
    -
    2006年03月

    慶應義塾, 医学部

    大学, 卒業

  • 2008年04月
    -
    2012年03月

    慶應義塾, 医学部, 医学科

    大学院, 単位取得退学, 博士

学位 【 表示 / 非表示

  • 博士(医学), 慶應義塾, 課程, 2014年09月

    Time-lapse imaging of cell cycle dynamics during development in living cardiomyocyte

免許・資格 【 表示 / 非表示

  • 医師免許, 2006年

  • 日本内科学会 認定内科医, 2009年

  • 日本循環器学会 循環器専門医, 2013年

  • Educational Commission for Foreign Medical Graduates Certificate, 2015年

  • 日本内科学会 総合内科専門医, 2019年

 

研究分野 【 表示 / 非表示

  • 分子生物学 (エピジェネティクス)

  • 発生生物学 (心臓発生)

  • 循環器内科学 (再生医学)

 

論文 【 表示 / 非表示

  • Stem Cell Aging in Skeletal Muscle Regeneration and Disease.

    Yamakawa H, Kusumoto D, Hashimoto H, Yuasa S

    International journal of molecular sciences 21 ( 5 )  2020年03月

  • Cardiac Reprogramming Factors Synergistically Activate Genome-wide Cardiogenic Stage-Specific Enhancers.

    Hashimoto H, Wang Z, Garry GA, Malladi VS, Botten GA, Ye W, Zhou H, Osterwalder M, Dickel DE, Visel A, Liu N, Bassel-Duby R, Olson EN

    Cell stem cell (Cell Stem Cell)  25 ( 1 ) 69 - 86.e5 2019年05月

    研究論文(学術雑誌), 共著, 査読有り,  ISSN  1934-5909

     概要を見る

    © 2019 Elsevier Inc. The cardiogenic transcription factors (TFs) Mef2c, Gata4, and Tbx5 can directly reprogram fibroblasts to induced cardiac-like myocytes (iCLMs), presenting a potential source of cells for cardiac repair. While activity of these TFs is enhanced by Hand2 and Akt1, their genomic targets and interactions during reprogramming are not well studied. We performed genome-wide analyses of cardiogenic TF binding and enhancer profiling during cardiac reprogramming. We found that these TFs synergistically activate enhancers highlighted by Mef2c binding sites and that Hand2 and Akt1 coordinately recruit other TFs to enhancer elements. Intriguingly, these enhancer landscapes collectively resemble patterns of enhancer activation during embryonic cardiogenesis. We further constructed a cardiac reprogramming gene regulatory network and found repression of EGFR signaling pathway genes. Consistently, chemical inhibition of EGFR signaling augmented reprogramming. Thus, by defining epigenetic landscapes these findings reveal synergistic transcriptional activation across a broad landscape of cardiac enhancers and key signaling pathways that govern iCLM reprogramming. Hashimoto and colleagues show that reprogramming factors act in concert at cardiac regulatory elements to directly reprogram mouse fibroblasts into induced cardiac-like myocytes (iCLMs). Moreover, cardiac reprogramming is achieved by activation of endogenous cardiac enhancers that initiate a cardiogenic gene regulatory network.

  • Therapeutic approaches for cardiac regeneration and repair

    Hashimoto H., Olson E., Bassel-Duby R.

    Nature Reviews Cardiology (Nature Reviews Cardiology)  15 ( 10 ) 585 - 600 2018年10月

    研究論文(学術雑誌), 共著, 査読有り,  ISSN  17595002

     概要を見る

    © 2018, Macmillan Publishers Ltd., part of Springer Nature. Ischaemic heart disease is a leading cause of death worldwide. Injury to the heart is followed by loss of the damaged cardiomyocytes, which are replaced with fibrotic scar tissue. Depletion of cardiomyocytes results in decreased cardiac contraction, which leads to pathological cardiac dilatation, additional cardiomyocyte loss, and mechanical dysfunction, culminating in heart failure. This sequential reaction is defined as cardiac remodelling. Many therapies have focused on preventing the progressive process of cardiac remodelling to heart failure. However, after patients have developed end-stage heart failure, intervention is limited to heart transplantation. One of the main reasons for the dramatic injurious effect of cardiomyocyte loss is that the adult human heart has minimal regenerative capacity. In the past 2 decades, several strategies to repair the injured heart and improve heart function have been pursued, including cellular and noncellular therapies. In this Review, we discuss current therapeutic approaches for cardiac repair and regeneration, describing outcomes, limitations, and future prospects of preclinical and clinical trials of heart regeneration. Substantial progress has been made towards understanding the cellular and molecular mechanisms regulating heart regeneration, offering the potential to control cardiac remodelling and redirect the adult heart to a regenerative state.

  • Epigenetic barrier against the propagation of fluctuating gene expression in embryonic stem cells.

    Saito Y, Kunitomi A, Seki T, Tohyama S, Kusumoto D, Takei M, Kashimura S, Hashimoto H, Yozu G, Motoda C, Shimojima M, Egashira T, Oda M, Fukuda K, Yuasa S

    FEBS letters (FEBS Letters)  591 ( 18 ) 2879 - 2889 2017年09月

    研究論文(学術雑誌), 共著, 査読有り,  ISSN  0014-5793

     概要を見る

    © 2017 Federation of European Biochemical Societies The expression of pluripotency genes fluctuates in a population of embryonic stem (ES) cells and the fluctuations in the expression of some pluripotency genes correlate. However, no correlation in the fluctuation of Pou5f1, Zfp42, and Nanog expression was observed in ES cells. Correlation between Pou5f1 and Zfp42 fluctuations was demonstrated in ES cells containing a knockout in the NuRD component Mbd3. ES cells containing a triple knockout in the DNA methyltransferases Dnmt1, Dnmt3a, and Dnmt3b showed correlation between the fluctuation of Pou5f1, Zfp42, and Nanog gene expression. We suggest that an epigenetic barrier is key to preventing the propagation of fluctuating pluripotency gene expression in ES cells.

  • ZNF281 enhances cardiac reprogramming by modulating cardiac and inflammatory gene expression.

    Zhou H, Morales MG, Hashimoto H, Dickson ME, Song K, Ye W, Kim MS, Niederstrasser H, Wang Z, Chen B, Posner BA, Bassel-Duby R, Olson EN

    Genes & development (Genes and Development)  31 ( 17 ) 1770 - 1783 2017年09月

    研究論文(学術雑誌), 共著, 査読有り,  ISSN  0890-9369

     概要を見る

    © 2017 Zhou et al. Direct reprogramming of fibroblasts to cardiomyocytes represents a potential means of restoring cardiac function following myocardial injury. AKT1 in the presence of four cardiogenic transcription factors, GATA4, HAND2, MEF2C, and TBX5 (AGHMT), efficiently induces the cardiac gene program in mouse embryonic fibroblasts but not adult fibroblasts. To identify additional regulators of adult cardiac reprogramming, we performed an unbiased screen of transcription factors and cytokines for those that might enhance or suppress the cardiogenic activity of AGHMT in adult mouse fibroblasts. Among a collection of inducers and repressors of cardiac reprogramming, we discovered that the zinc finger transcription factor 281 (ZNF281) potently stimulates cardiac reprogramming by genome-wide association with GATA4 on cardiac enhancers. Concomitantly, ZNF281 suppresses expression of genes associated with inflammatory signaling, suggesting the antagonistic convergence of cardiac and inflammatory transcriptional programs. Consistent with an inhibitory influence of inflammatory pathways on cardiac reprogramming, blockade of these pathways with anti-inflammatory drugs or components of the nucleosome remodeling deacetylase (NuRD) complex, which associate with ZNF281, stimulates cardiac gene expression. We conclude that ZNF281 acts at a nexus of cardiac and inflammatory gene programs, which exert opposing influences on fibroblast to cardiac reprogramming.

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KOARA(リポジトリ)収録論文等 【 表示 / 非表示

総説・解説等 【 表示 / 非表示

  • Epigenetic barrier against the propagation of fluctuating gene expression in embryonic stem cells

    Saito Y., Kunitomi A., Seki T., Tohyama S., Kusumoto D., Takei M., Kashimura S., Hashimoto H., Yozu G., Motoda C., Shimojima M., Egashira T., Oda M., Fukuda K., Yuasa S.

    FEBS Letters (FEBS Letters)  591 ( 18 ) 2879 - 2889 2017年09月

    ISSN  00145793

     概要を見る

    © 2017 Federation of European Biochemical Societies The expression of pluripotency genes fluctuates in a population of embryonic stem (ES) cells and the fluctuations in the expression of some pluripotency genes correlate. However, no correlation in the fluctuation of Pou5f1, Zfp42, and Nanog expression was observed in ES cells. Correlation between Pou5f1 and Zfp42 fluctuations was demonstrated in ES cells containing a knockout in the NuRD component Mbd3. ES cells containing a triple knockout in the DNA methyltransferases Dnmt1, Dnmt3a, and Dnmt3b showed correlation between the fluctuation of Pou5f1, Zfp42, and Nanog gene expression. We suggest that an epigenetic barrier is key to preventing the propagation of fluctuating pluripotency gene expression in ES cells.

  • Induction of Cardiac Cell Types by Direct Reprogramming

    Hisayuki Hashimoto, Huanyu Zhou, Maria G. Morales, Maria Abad, Rhonda Bassel-Duby, Eric N. Olson

    CIRCULATION RESEARCH (LIPPINCOTT WILLIAMS & WILKINS)  119 ( 12 ) E168 - E168 2016年12月

    研究発表要旨(国際会議), 共著,  ISSN  0009-7330

  • Novel Method 'Fucci' Elucidated the Cardiomyocyte Cell Cycle Dynamics in Various Life Stages

    Hisayuki Hashimoto, Shinsuke Yuasa, Shugo Tohyama, Tomohisa Seki, Toru Egashira, Kojiro Yae, Dai Kusumoto, Masaki Kodaira, Fumiyuki Hattori, Naoto Muraoka, Hidenori Tabata, Kazunori Nakajima, Asako Sakaue-Sawano, Atsushi Miyawaki, Keiichi Fukuda

    CIRCULATION (LIPPINCOTT WILLIAMS & WILKINS)  122 ( 21 )  2010年11月

    研究発表要旨(国際会議), 共著,  ISSN  0009-7322

  • ヒトiPS由来心筋細胞の電気生理学的特性について

    遠山 周吾, 村田 光繁, 黒川 洵子, Fernando Lopez-Redondo, 服部 文幸, 水澤 美香, 山川 裕之, 橋本 寿之, 江頭 徹, 関 朋久, 扇野 泰行, 八戸 宏二郎, 湯浅 慎介, 福田 恵一

    心電図 ((一社)日本不整脈心電学会)  30 ( Suppl.4 ) S - 4 2010年09月

    その他記事, 共著,  ISSN  0285-1660

  • Functional Characterization of Human Induced Pluripotent Stem Cell Derived Cardiomyocytes

    Shugo Tohyama, Mitsushige Murata, Fumiyuki Hattori, Tomofumi Tanaka, Hao Chen, Hiromi Yamashita, Yusuke Sato, Toru Egashira, Tomohisa Seki, Hisayuki Hashimoto, Yohei Ohno, Yuichi Tamura, Shinsuke Yuasa, Satoshi Ogawa, Keiichi Fukuda

    CIRCULATION (LIPPINCOTT WILLIAMS & WILKINS)  120 ( 18 ) S723 - S723 2009年11月

    研究発表要旨(国際会議), 共著,  ISSN  0009-7322

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研究発表 【 表示 / 非表示

  • エピジェネティクス解析を用いた心筋リプログラミングの分子機構の解明

    橋本 寿之

    第40回日本循環制御医学会 総会・学術集会, 2019年06月, 口頭(一般)

  • Synergistic Activation of the Cardiac Enhancer Landscape During Reprogramming

    橋本 寿之

    第83回日本循環器学会学術集会, 2019年03月, 口頭(一般)

  • Induction of Cardiac Cell Types by Direct Reprogramming

    橋本 寿之

    American Heart Association Scientific Sessions, 2016年11月, ポスター(一般)

  • Induction of Diverse Cardiac Cell Types by Direct Reprogramming

    橋本 寿之

    American Heart Association Scientific Council on Basic Cardiovascular Sciences, 2016年07月, 口頭(招待・特別)

  • A Novel Cardiac ex vivo Culture System Revealed the Elongation of Cell Cycle Phases in Cardiomyocytes During Development

    橋本 寿之

    国際心臓研究学会日本部会総会, 2013年06月, 口頭(一般)

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競争的資金等の研究課題 【 表示 / 非表示

  • 心臓発生における転写因子ZNF281の心筋分化調節機構の解明

    2019年04月
    -
    2022年03月

    慶應義塾大学, 橋本 寿之, 若手研究

     研究概要を見る

    申請者は転写因子Zinc Finger Protein 281(ZNF281)には、線維芽細胞を心筋様細胞に直接リプログラミングする効率を著明に改善する機能があることを以前明らかにした。本研究ではこのZNF281の心筋誘導作用に着目し、胚性幹細胞(ES細胞)及びマウスを用いて心筋分化と心臓発生におけるZNF281の転写調節機構と作用を解明する。本研究成果はZNF281を利用した新たな心臓再生技術の開発につながる可能性があるだけでなく、心臓形成に関わる新規制御因子を探索するデータベースとしてのリプログラミング法の新たな利用価値を立証することとなる。

受賞 【 表示 / 非表示

  • Young Investigator’s Award

    2013年, International Society of Heart Research Japanese Section

    受賞区分: 国内学会・会議・シンポジウム等の賞

  • International Poster Prize Award

    2010年, International Society of Heart Research World Congress

    受賞区分: 国際学会・会議・シンポジウム等の賞,  受賞国: 日本