KEIO RESEARCHERS INFORMATION SYSTEM

Career 【 Display / hide 】

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

Academic Background 【 Display / hide 】

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

Research Areas 【 Display / hide 】

Research Areas 【 Display / hide 】

• Life Science / Neuroscience-general

• Life Science / Immunology

Papers 【 Display / hide 】

Papers 【 Display / hide 】

• Immune checkpoint LAG-3 governs stage-dependent and disease-associated microglial modules in ALS model mice

  Yuta Morisaki, Nanaka Nomura, Motoki Ohshima, Miruto Matsuda, Okiru Komine, Takashi Okuda, Koji Yamanaka, Hidemi Misawa

  Journal of Neuroinflammation   2026.06

  Research paper (scientific journal), Joint Work, Lead author, Corresponding author, Accepted,  ISSN  1742-2094

  　View Summary

  Immune checkpoint molecules, inhibitory receptors originally characterized in T cell biology, have recently emerged as regulators of microglial function in neurodegeneration, yet their roles in amyotrophic lateral sclerosis (ALS) remain unexplored. Here, we investigated LAG-3, an inhibitory immune checkpoint receptor, in microglial regulation during ALS pathogenesis using SOD1G93A mice. LAG-3 expression was progressively upregulated in spinal cord microglia during disease progression, and LAG-3-high microglia exhibited a disease-associated microglia (DAM) transcriptional signature. Genetic deletion of LAG-3 produced a biphasic phenotype, with accelerated disease onset but significantly prolonged disease duration. LAG-3 deficiency enhanced inflammatory microglial responses at the early disease stage, whereas at the late stage it suppressed inflammatory signaling while selectively preserving phagocytic effector gene expression, demonstrating that LAG-3 dissociates the inflammatory and phagocytic modules within the DAM program in a stage-dependent manner. These transcriptional changes translated into enhanced phagocytic capacity in primary microglia and amelioration of the spinal cord environment through suppression of inflammatory pathways and restoration of oxidative phosphorylation. Our findings identify LAG-3 as a stage-dependent regulator of microglial functional states in ALS and support the concept that immune checkpoint molecules constitute a class of module-level regulators of microglial function in neurodegeneration.

• 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.

  • Access to Document (DOI)

• 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.

  • Access to Document (DOI)

• 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

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Reviews, Commentaries, etc. 【 Display / hide 】

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

Presentations 【 Display / hide 】

Presentations 【 Display / hide 】

• LAG-3 exhibits stage-dependent regulation of microglial inflammation and phagocytosis in ALS

  Yuta Morisaki, Nanaka Nomura, Motoki Ohshima, Okiru Komine, Koji Yamanaka, Hidemi Misawa

  NEURO2026（第49回日本神経科学学会）, 

  2026.07

  -

  2026.08

  , 

  Poster presentation

• Disulfide-dependent formation of SDS-resistant aggregates in ALS-associated SOD1

  相川香乃, 森﨑祐太, 三澤日出巳, 古川良明

  第26回日本蛋白質科学会年会, 

  2026.06

  , 

  Poster presentation

• ニコチン性アセチルコリン受容体調節因子 Ly6H の脳内発現領域の同定

  岩瀬陸人, 森﨑祐太, 揣雅涵, 三澤日出巳, 辻祥太郎, 井上直和, 田中謙二, 森脇康博

  [Domestic presentation]  日本薬学会第146年会 , 

  2026.03

  , 

  Poster presentation

• Identification and Characterization of Fizz1 as a Novel Therapeutic Target for Chronic Itch

  Miruto Matsuda, Naoki Sekigawa, Yui Endo, Toshiki Imanaka, Yuta Morisaki, Hidemi Misawa

  [Domestic presentation]  第99回薬理学会年会, 

  2026.03

  , 

  Poster presentation

• 免疫チェックポイント分子LAG-3はJAK-STATシグナル伝達経路の阻害を介してミクログリアの活性化を抑制する

  大島基希,森﨑祐太,三澤日出巳

  第153回日本薬理学会関東部会, 

  2025.10

  , 

  Symposium, workshop panel (public)

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Awards 【 Display / hide 】

Awards 【 Display / hide 】

• LEGEND Research Grant Program 2025

  2025.10, BioLegend Japan株式会社、トミーデジタルバイオロジー株式会社, ALSにおける末梢神経マクロファージの病態制御機構の解明と新規治療標的の探索

• 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.

Courses Taught 【 Display / hide 】

Courses Taught 【 Display / hide 】

• PHARMACOLOGY FOR NURSING AND HEALTH CARE

  2026

• PHARMACOLOGY 2

  2026

• MOLECULAR ONCOLOGY AND NEUROSCIENCE

  2026

• PHARMACOLOGY LABORATORY COURSE

  2026

• PHARMACOLOGY 1

  2026

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