Morisaki, Yuta

写真a

Affiliation

Faculty of Pharmacy, Department of Pharmaceutical Sciences 薬理学講座 （Shiba-Kyoritsu）

Position

Research Associate/Assistant Professor/Instructor

External Links
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Career 【 Display / hide 】

  • 2016.04
    -
    2019.11

    科研製薬株式会社, 新薬創生センター, 研究員

  • 2019.12
    -
    2021.07

    ブリストル・マイヤーズ スクイブ株式会社, メディカル部門, メディカルサイエンスリエゾン

  • 2021.08
    -
    Present

    慶應義塾大学　薬学部　薬理学講座, 助教

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Academic Background 【 Display / hide 】

  • 2010.04
    -
    2014.03

    Keio University, 薬学部, 薬科学科

    University, Graduated

  • 2014.04
    -
    2016.03

    Keio University, 薬学研究科, 薬科学専攻

    Graduate School, Completed, Master's course

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Research Areas 【 Display / hide 】

  • Life Science / Neuroscience-general

  • Life Science / Immunology

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Papers 【 Display / hide 】

  • Type selective ablation of postnatal slow and fast fatigue-resistant motor neurons in mice induces late onset kinetic and postural tremor following fiber-type transition and myopathy

    Hidemi Misawa, Kai Kamishima, Tenkei Koyama, Lisa Ohgaki, Yuta Morisaki, Tomoyuki Yamanaka, Shigeyoshi Itohara, Shoko Sawano, Wataru Mizunoya, Naomichi Ogihara

    Experimental Neurology （Elsevier)  376 2024.04

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  00144886

    　View Summary

    Animals on Earth need to hold postures and execute a series of movements under gravity and atmospheric pressure. VAChT-Cre is a transgenic Cre driver mouse line that expresses Cre recombinase selectively in motor neurons of S-type (slow-twitch fatigue-resistant) and FR-type (fast-twitch fatigue-resistant). Sequential motor unit recruitment is a fundamental principle for fine and smooth locomotion; smaller-diameter motor neurons (S-type, FR-type) first contract low-intensity oxidative type I and type IIa muscle fibers, and thereafter larger-diameter motor neurons (FInt-type, FF-type) are recruited to contract high-intensity glycolytic type IIx and type IIb muscle fibers. To selectively eliminate S- and FR-type motor neurons, VAChT-Cre mice were crossbred with NSE-DTA mice in which the cytotoxic diphtheria toxin A fragment (DTA) was expressed in Cre-expressing neurons. The VAChT-Cre;NSE-DTA mice were born normally but progressively manifested various characteristics, including body weight loss, kyphosis, kinetic and postural tremor, and muscular atrophy. The progressive kinetic and postural tremor was remarkable from around 20 weeks of age and aggravated. Muscular atrophy was apparent in slow muscles, but not in fast muscles. The increase in motor unit number estimation was detected by electromyography, reflecting compensatory re-innervation by remaining FInt- and FF-type motor neurons to the orphaned slow muscle fibers. The muscle fibers gradually manifested fast/slow hybrid phenotypes, and the remaining FInt-and FF-type motor neurons gradually disappeared. These results suggest selective ablation of S- and FR-type motor neurons induces progressive muscle fiber-type transition, exhaustion of remaining FInt- and FF-type motor neurons, and late-onset kinetic and postural tremor in mice.

  • LAG-3 expression in microglia regulated by IFN-γ/STAT1 pathway and metalloproteases

    Yuta Morisaki, Motoki Ohshima, Hikaru Suzuki, Hidemi Misawa

    Frontiers in Cellular Neuroscience （Frontiers in Cellular Neuroscience)  17 2023.11

    Research paper (scientific journal), Joint Work, Lead author, Corresponding author, Accepted,  ISSN  16625102

    　View Summary

    Microglia are resident innate immune cells in the central nervous system (CNS) and play important roles in the development of CNS homeostasis. Excessive activation and neurotoxicity of microglia are observed in several CNS disorders, but the mechanisms regulating their activation remain unclear. Immune checkpoint molecules are expressed on activated immune cells and regulate their activation in peripheral immunity. However, the expression mechanism of immune checkpoint molecules in activated microglia is still unknown. Here, we analyzed the expression of immune checkpoint molecules in activated microglia using the mouse microglial cell line BV2 and primary cultured microglia. The expression of lymphocyte activation gene-3 (LAG-3), a type of immune checkpoint molecule, was increased in microglia activated by IFN-γ. IFN-γ-induced LAG-3 expression in microglia was suppressed by transfection of siRNA targeting STAT1. LAG-3 has two forms, membrane and soluble, and both forms were upregulated in microglia activated by IFN-γ. The production of soluble LAG-3 was suppressed by treatment with inhibitors of metalloproteinases such as ADAM10 and ADAM17. IFN-γ administration into cisterna magna of mice increased LAG-3 expression in spinal microglia. Furthermore, LAG-3 knockdown in microglia promoted nitric oxide production by IFN-γ. Our results demonstrate that LAG-3 expression in microglia is induced by the IFN-γ-STAT1 pathway and soluble LAG-3 production is regulated via cleavage of membranous LAG-3 by metalloproteinases including ADAM10 and ADAM17.

  • Depletion of perivascular macrophages delays ALS disease progression by ameliorating blood-spinal cord barrier impairment in SOD1-G93A mice

    Kazuki Adachi, Kota Miyata, Yukino Chida, Mikako Hirose, Yuta Morisaki, Koji Yamanaka, Hidemi Misawa

    Frontiers in Cellular Neuroscience  2023.11

    Research paper (scientific journal), Joint Work, Accepted

  • A copper-deficient form of mutant Cu/Zn-superoxide dismutase as an early pathological species in amyotrophic lateral sclerosis

    Tokuda Eiichi, Nomura Takao, Ohara Shinji, Watanabe Seiji, Yamanaka Koji, Morisaki Yuta, Misawa Hidemi, Furukawa Yoshiaki

    Biochimica et Biophysica Acta - Molecular Basis of Disease  2018.06

    Research paper (scientific journal), Joint Work, Accepted

  • Immunochemical characterization on pathological oligomers of mutant Cu/Zn-superoxide dismutase in amyotrophic lateral sclerosis

    Tokuda Eiichi, Anzai Itsuki, Nomura Takao, Toichi Keisuke, Watanabe Masahiko, Ohara Shinji, Watanabe Seiji, Yamanaka Koji, Morisaki Yuta, Misawa Hidemi, Furukawa Yoshiaki

    Molecular Neurodegeneration  2017.01

    Research paper (scientific journal), Joint Work, Accepted

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Reviews, Commentaries, etc. 【 Display / hide 】

  • 運動ニューロンサブタイプとALSにおける選択的脆弱性の解析

    三澤日出巳、森﨑祐太

    日薬理誌 (日本薬理学会)   2018.08

    Article, review, commentary, editorial, etc. (scientific journal), Joint Work

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Presentations 【 Display / hide 】

  • Expression and function analysis of immune checkpoint molecule LAG-3 in microglia

    Motoki Ohshima, Yuta Morisaki, Hidemi Misawa

    第97回日本薬理学会年会, 

    2023.12
    , 

    Oral presentation (general)

  • PD-1 immune checkpoint blockade accelerates disease progression in a mouse model of amyotrophic lateral sclerosis

    Yuta Morisaki, Ran Aono, Hikaru Suzuki, Motoki Ohshima, Koji Yamanaka, Hidemi Misawa

    NEURO2023（第46回日本神経科学学会）, 

    2023.08
    , 

    Poster presentation

  • Expression analysis of immune checkpoint molecules in microglia

    Motoki Ohshima, Yuta Morisaki, Koji Yamanaka, Hidemi Misawa

    NEURO2023（第46回日本神経科学学会）, 

    2023.08
    , 

    Oral presentation (general)

  • Expression and distribution of immune checkpoint molecules LAG-3 in amyotrophic lateral sclerosis

    Motoki Ohshima;Hiroto Aoki;Ran Aono;Yuta Morisaki;Koji Yamanaka;Hidemi Misawa

    JPW2022 （第96回日本薬理学会年会 / 第43回日本臨床薬理学会学術総会）, 

    2022.11
    -
    2022.12
    , 

    Poster presentation

  • Expression patterns of immune exhaustion molecules in the mouse model of amyotrophic lateral sclerosis

    Yuta Morisaki, Ran Aono, Motoki Ohshima, Ami Okabe, Mayo Teragawa, Koji Yamanaka, Hidemi Misawa

    NEURO2022, 

    2022.06
    -
    2022.07
    , 

    Poster presentation

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Awards 【 Display / hide 】

  • 第131回日本薬理学会関東部会 若手優秀発表賞

    森﨑祐太、坪田充司、森脇康博、山中宏二、三澤日出巳, 2014.10, 運動ニューロンのサブタイプ選択的脆弱性におけるオステオポンチンとマトリックスメタロプロテアーゼ-9の役割

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

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Courses Taught 【 Display / hide 】

  • RESEARCH FOR BACHELOR'S THESIS 1

    2024

  • ENGLISH EXERCISES FOR PHARMACEUTICAL SCIENCES

    2024

  • BACHELOR'S THESIS

    2024

  • PHARMACOLOGY LABORATORY COURSE

    2024

  • PHARMACOLOGY FOR NURSING AND HEALTH CARE

    2024

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