Hashimoto, Hisayuki

写真a

Affiliation

School of Medicine, Joint Research Laboratory for Medical Innovation in Heart Disease (Shinanomachi)

Position

Project Senior Assistant Professor (Non-tenured)/Project Assistant Professor (Non-tenured)/Project Lecturer (Non-tenured)

External Links

Other Affiliation 【 Display / hide

  • 医学部, 循環器内科学教室, 特任講師

Career 【 Display / hide

  • 2006.04
    -
    2008.03

    栃木県済生会宇都宮病院, 初期臨床研修医

  • 2008.04
    -
    2009.03

    慶應義塾大学病院 内科学教室, 専修医

  • 2009.04
    -
    2011.03

    Keio University, School of Medicine, 「幹細胞医学のための教育研究拠点」研究員

  • 2011.04
    -
    2012.03

    Keio University, 医学研究科, 助教(研究奨励)

  • 2012.04
    -
    2014.03

    Keio University, School of Medicine Department of Internal Medicine (Cardiology), 助教

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Academic Background 【 Display / hide

  • 1998.04
    -
    2000.03

    慶應義塾高等学校

  • 2000.04
    -
    2006.03

    Keio University, School of Medicine

  • 2008.04
    -
    2012.03

    Keio University, Graduate School of Medicine, 内科学

Academic Degrees 【 Display / hide

  • Doctor(Medicine), Keio University, Coursework, 2014.09

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

Licenses and Qualifications 【 Display / hide

  • 医師免許, 2006

  • 日本内科学会 認定内科医, 2009

  • 日本循環器学会 循環器専門医, 2013

  • Educational Commission for Foreign Medical Graduates Certificate, 2015

  • 日本内科学会 総合内科専門医, 2019

 

Research Areas 【 Display / hide

  • Life Science / Molecular biology (エピジェネティクス)

  • Life Science / Genome biology

  • Life Science / Developmental biology (心臓発生)

  • Life Science / Anatomy

  • Life Science / Pathological biochemistry

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Research Keywords 【 Display / hide

  • エピジェネティクス

  • リプログラミング

  • 再生医療

  • 分子生物学

  • 幹細胞

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Papers 【 Display / hide

  • The histone reader PHF7 cooperates with the SWI/SNF complex at cardiac super enhancers to promote direct reprogramming.

    Glynnis A Garry, Svetlana Bezprozvannaya, Kenian Chen, Huanyu Zhou, Hisayuki Hashimoto, Maria Gabriela Morales, Ning Liu, Rhonda Bassel-Duby, Eric N Olson

    Nature cell biology (Nature Cell Biology)  23 ( 5 ) 467 - 475 2021.05

    ISSN  1465-7392

     View Summary

    Direct cardiac reprogramming of fibroblasts to cardiomyocytes presents an attractive therapeutic strategy to restore cardiac function following injury. Cardiac reprogramming was initially achieved through overexpression of the transcription factors Gata4, Mef2c and Tbx5; later, Hand2 and Akt1 were found to further enhance this process1-5. Yet, staunch epigenetic barriers severely limit the ability of these cocktails to reprogramme adult fibroblasts6,7. We undertook a screen of mammalian gene regulatory factors to discover novel regulators of cardiac reprogramming in adult fibroblasts and identified the histone reader PHF7 as the most potent activating factor8. Mechanistically, PHF7 localizes to cardiac super enhancers in fibroblasts, and through cooperation with the SWI/SNF complex, it increases chromatin accessibility and transcription factor binding at these sites. Furthermore, PHF7 recruits cardiac transcription factors to activate a positive transcriptional autoregulatory circuit in reprogramming. Importantly, PHF7 achieves efficient reprogramming in the absence of Gata4. Here, we highlight the underexplored necessity of cardiac epigenetic readers, such as PHF7, in harnessing chromatin remodelling and transcriptional complexes to overcome critical barriers to direct cardiac reprogramming.

  • Anti-senescent drug screening by deep learning-based morphology senescence scoring.

    Dai Kusumoto, Tomohisa Seki, Hiromune Sawada, Akira Kunitomi, Toshiomi Katsuki, Mai Kimura, Shogo Ito, Jin Komuro, Hisayuki Hashimoto, Keiichi Fukuda, Shinsuke Yuasa

    Nature communications (Nature Communications)  12 ( 1 ) 257 - 257 2021.01

     View Summary

    Advances in deep learning technology have enabled complex task solutions. The accuracy of image classification tasks has improved owing to the establishment of convolutional neural networks (CNN). Cellular senescence is a hallmark of ageing and is important for the pathogenesis of ageing-related diseases. Furthermore, it is a potential therapeutic target. Specific molecular markers are used to identify senescent cells. Moreover senescent cells show unique morphology, which can be identified. We develop a successful morphology-based CNN system to identify senescent cells and a quantitative scoring system to evaluate the state of endothelial cells by senescence probability output from pre-trained CNN optimised for the classification of cellular senescence, Deep Learning-Based Senescence Scoring System by Morphology (Deep-SeSMo). Deep-SeSMo correctly evaluates the effects of well-known anti-senescent reagents. We screen for drugs that control cellular senescence using a kinase inhibitor library by Deep-SeSMo-based drug screening and identify four anti-senescent drugs. RNA sequence analysis reveals that these compounds commonly suppress senescent phenotypes through inhibition of the inflammatory response pathway. Thus, morphology-based CNN system can be a powerful tool for anti-senescent drug screening.

  • Dermal fibroblast-like cells reprogrammed directly from adipocytes in mouse.

    Mitsunobu Toyosaki, Koichiro Homma, Sayuri Suzuki, Naoto Muraoka, Hisayuki Hashimoto, Naoki Goshima, Masaki Ieda, Junichi Sasaki

    Scientific reports (Scientific Reports)  10 ( 1 ) 21467 - 21467 2020.12

     View Summary

    In deep burns, early wound closure is important for healing, and skin grafting is mainly used for wound closure. However, it is difficult to achieve early wound closure in extensive total body surface area deep burns due to the lack of donor sites. Dermal fibroblasts, responsible for dermis formation, may be lost in deep burns. However, fat layers composed of adipocytes, lying underneath the dermis, are retained even in such cases. Direct reprogramming is a novel method for directly reprograming some cells into other types by introducing specific master regulators; it has exhibited appreciable success in various fields. In this study, we aimed to assess whether the transfection of master regulators (ELF4, FOXC2, FOXO1, IRF1, PRRX1, and ZEB1) could reprogram mouse adipocytes into dermal fibroblast-like cells. Our results indicated the shrinkage of fat droplets in reprogrammed mouse adipocytes and their transformation into spindle-shaped dermal fibroblasts. Reduced expression of PPAR-2, c/EBP, aP2, and leptin, the known markers of adipocytes, in RT-PCR, and enhanced expression of anti-ER-TR7, the known anti-fibroblast marker, in immunocytochemistry, were confirmed in the reprogrammed mouse adipocytes. The dermal fibroblast-like cells, reported here, may open up a new treatment mode for enabling early closure of deep burn wounds.

  • Stem Cell Aging in Skeletal Muscle Regeneration and Disease.

    Yamakawa H, Kusumoto D, Hashimoto H, Yuasa S

    International journal of molecular sciences 21 ( 5 )  2020.03

  • 補体副経路を標的とした右心不全および心室性不整脈に対する新たな治療法の開発

    伊藤 章吾, 湯浅 慎介, 小室 仁, 勝木 俊臣, 木村 舞, 岸野 喜一, 楠本 大, 橋本 寿之, 鈴木 邦道, 柚崎 通介, 福田 恵一

    補体 ((一社)日本補体学会)  56 ( 1 ) 55 - 56 2019.07

    ISSN  2188-8205

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Papers, etc., Registered in KOARA 【 Display / hide

Reviews, Commentaries, etc. 【 Display / hide

  • 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 2017.09

    ISSN  00145793

     View Summary

    © 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 2016.12

    Research paper, summary (international conference), Joint Work,  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 )  2010.11

    Research paper, summary (international conference), Joint Work,  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 2010.09

    Other, Joint Work,  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 2009.11

    Research paper, summary (international conference), Joint Work,  ISSN  0009-7322

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Presentations 【 Display / hide

  • Dissecting the Molecular Mechanism of Cardiac Reprogramming by Epigenetic Analysis

    Hisayuki Hashimoto

    日本再生医療学会, 

    2020.03

    Oral presentation (invited, special)

  • 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, 

    2019.06

    Oral presentation (general)

  • Synergistic Activation of the Cardiac Enhancer Landscape During Reprogramming

    Hashimoto Hisayuki

    The 83rd Annual Scientific Meeting of the Japanese Circulation Society, 

    2019.03

    Oral presentation (general)

  • Induction of Cardiac Cell Types by Direct Reprogramming

    Hashimoto Hisayuki

    American Heart Association Scientific Sessions, 

    2016.11

    Poster presentation

  • Induction of Diverse Cardiac Cell Types by Direct Reprogramming

    Hashimoto Hisayuki

    American Heart Association Scientific Council on Basic Cardiovascular Sciences, 

    2016.07

    Oral presentation (invited, special)

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • 分化転換誘導因子が司る臓器形成の分子機序解明

    2022.04
    -
    2025.03

    日本学術振興会, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), No Setting

  • エピゲノム編集による心筋分化転換法の確立

    2021
    -
    2023

    日本循環器学会, 基礎研究助成, Principal investigator

  • SARS-CoV-2 細胞侵入受容体の発現調節経路を標的としたCOVID-19 の新規治療戦略

    2020
    -
    2021

    公益財団法人 東京生化学研究会, 研究奨励金, Principal investigator

  • Synergistic Activation of the Cardiac Enhancer Landscape During Reprogramming

    2019.09

    The Ichiro Kanehara Foundation, Grant-in-Aid for Research Exchange, Hisayuki Hashimoto, Principal investigator

  • 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

    2019.04
    -
    2022.03

    Keio University, Grants-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists, Research grant, Principal investigator

     View Summary

    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。

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Awards 【 Display / hide

  • 医学研究賞

    橋本 寿之, 2021.03, 東京都医師会

  • 循環器再生医科学賞

    橋本 寿之, 2020.08, 日本循環器学会

  • Keio University School of Medicine Alumni Association (Sanshikai) Young Investigator Award

    2020.04, Keio University

  • 第14回循環器再生医科学賞(基礎研究)

    2020, 日本循環器学会

    Type of Award: Award from Japanese society, conference, symposium, etc.

  • 総会・学術集会 会長賞

    橋本 寿之, 2019.06, 日本循環制御医学会

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Courses Taught 【 Display / hide

  • PHYSICAL ASSESSMENT

    2022

  • PATHOPHYSIOLOGICAL ISSUES IN CHRONIC CARE

    2022

  • CLINICAL ENGINEERING AND SAFETY CONTROL IN HEALTH CARE

    2022

  • Cardiology

    2019, Other, Lecture, Within own faculty

Courses Previously Taught 【 Display / hide

  • Medical Engineering in Cardiology

    Keio University School of Nursing

    2022
    -
    Present

    Postgraduate

  • Chronic Pathophysiology

    Keio University School of Nursing

    2022
    -
    Present

    Undergraduate (specialized)

  • Phyisical Assessment in Cardiology

    Keio University School of Nursing

    2022
    -
    Present

    Postgraduate

  • OSCE(Objective Structured Clinical Examination)

    Keio University

    2018
    -
    Present

  • Cardiology

    Keio University

    2018
    -
    Present

Educational Activities and Special Notes 【 Display / hide

  • OSCE

    2020

    , Special Affairs about A person who has work experience

  • 医学部カリキュラム委員

    2019
    -
    2020

    , Special Affairs

 

Memberships in Academic Societies 【 Display / hide

  • 日本再生医療学会, 

    2020.03
    -
    Present