Updated on 2025/03/31

写真a

 
WAKE Hiroaki
 
Organization
Institutes of Innovation for Future Society Institute of Quantum Chemistry Innovation Professor
Graduate School of Medicine Professor
Graduate School
Graduate School of Medicine
Title
Professor

Degree 1

  1. 医学博士 ( 2007.3   名古屋市立大学 ) 

Research Interests 6

  1. 脳梗塞

  2. 神経-グリア相関

  3. 生体

  4. ミクログリア

  5. シナプス

  6. 2光子励起顕微鏡

Research Areas 5

  1. Life Science / Clinical pharmacy

  2. Life Science / Neuroscience-general

  3. Life Science / Neuroscience-general

  4. Life Science / Neuroscience-general

  5. Life Science / Physiology

Research History 3

  1. National Institute for Physiological Sciences, National Institute of Natural Sciences   Division of Multicellular Circuit Dynamics   Professor

    2021.9

  2. Nagoya University   Professor

    2019.11

  3. Kobe University   Graduate School of Medicine   Professor

    2016.4 - 2019.10

Education 1

  1. 名古屋市立大学 大学院医学研究科博士課程生体情報機能制御医学専攻修了

    - 2007.3

Awards 1

  1. 神戸大学優秀若手研究賞・学長賞

    2017   神戸大学   高次脳機能の解明と操作に光を当てる

    WAKE HIROAKI

 

Papers 74

  1. Propagation of neuronal micronuclei regulates microglial characteristics

    Sarasa Yano, Natsu Asami, Yusuke Kishi, Ikuko Takeda, Hikari Kubotani, Yuki Hattori, Ayako Kitazawa, Kanehiro Hayashi, Ken-ichiro Kubo, Mai Saeki, Chihiro Maeda, Chihiro Hiraki, Rin-ichiro Teruya, Takumi Taketomi, Kaito Akiyama, Tomomi Okajima-Takahashi, Ban Sato, Hiroaki Wake, Yukiko Gotoh, Kazunori Nakajima, Takeshi Ichinohe, Takeshi Nagata, Tomoki Chiba, Fuminori Tsuruta

    Nature Neuroscience   Vol. 28 ( 3 ) page: 487 - 498   2025.3

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    DOI: 10.1038/s41593-024-01863-5

    Web of Science

    Scopus

    PubMed

    Other Link: https://www.nature.com/articles/s41593-024-01863-5

  2. Bone marrow niches orchestrate stem-cell hierarchy and immune tolerance. International journal

    Kazuhiro Furuhashi, Miwako Kakiuchi, Ryosuke Ueda, Hiroko Oda, Simone Ummarino, Alexander K Ebralidze, Mahmoud A Bassal, Chen Meng, Tatsuyuki Sato, Jing Lyu, Min-Guk Han, Shoichi Maruyama, Yu Watanabe, Yuriko Sawa, Daisuke Kato, Hiroaki Wake, Boris Reizis, John A Frangos, David M Owens, Daniel G Tenen, Ionita C Ghiran, Simon C Robson, Joji Fujisaki

    Nature   Vol. 638 ( 8049 ) page: 206 - 215   2025.1

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    Language:English   Publishing type:Research paper (scientific journal)  

    Stem cells reside in specialized microenvironments, termed niches, at several different locations in tissues1-3. The differential functions of heterogeneous stem cells and niches are important given the increasing clinical applications of stem-cell transplantation and immunotherapy. Whether hierarchical structures among stem cells at distinct niches exist and further control aspects of immune tolerance is unknown. Here we describe previously unknown new hierarchical arrangements in haematopoietic stem cells (HSCs) and bone marrow niches that dictate both regenerative potential and immune privilege. High-level nitric oxide-generating (NOhi) HSCs are refractory to immune attack and exhibit delayed albeit robust long-term reconstitution. Such highly immune-privileged, primitive NOhi HSCs co-localize with distinctive capillaries characterized by primary ciliated endothelium and high levels of the immune-checkpoint molecule CD200. These capillaries regulate the regenerative functions of NOhi HSCs through the ciliary protein IFT20 together with CD200, endothelial nitric oxide synthase and autophagy signals, which further mediate immunoprotection. Notably, previously described niche constituents, sinusoidal cells and type-H vessels2-10 co-localize with less immune-privileged and less potent NOlow HSCs. Together, we identify highly immune-privileged, late-rising primitive HSCs and characterize their immunoprotective niches comprising specialized vascular domains. Our results indicate that the niche orchestrates hierarchy in stem cells and immune tolerance, and highlight future immunotherapeutic targets.

    DOI: 10.1038/s41586-024-08352-6

    Web of Science

    Scopus

    PubMed

  3. 新たな肺腺癌脳転移モデルを用いた抗PD-1/CTLA-4抗体併用療法の有効性と作用機序の検討(Novel Model of Lung Adenocarcinoma Brain Metastasis Reveals Efficacy of Anti-PD-1/CTLA-4 Combination Therapy)

    細谷 和貴, 小笹 裕晃, 辻 貴宏, 島 佑介, 住永 圭一郎, 橋本 健太郎, 吉田 寛, 味水 瞳, 船造 智子, 吉田 博徳, 野溝 岳, 和氣 弘明, 平井 豊博, 辻 貴宏

    日本癌学会総会記事   Vol. 83回   page: P - 3090   2024.9

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    Language:English   Publisher:(一社)日本癌学会  

  4. Neuromodulation with transcranial direct current stimulation contributes to motor function recovery via microglia in spinal cord injury. International journal Open Access

    Ryotaro Oishi, Ikuko Takeda, Yukihito Ode, Yuya Okada, Daisuke Kato, Hiroaki Nakashima, Shiro Imagama, Hiroaki Wake

    Scientific reports   Vol. 14 ( 1 ) page: 18031 - 18031   2024.8

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    Language:English   Publishing type:Research paper (scientific journal)  

    Spinal cord injury (SCI) is damage or trauma to the spinal cord, which often results in loss of function, sensation, or mobility below the injury site. Transcranial direct current stimulation (tDCS) is a non-invasive and affordable brain stimulation technique used to modulate neuronal circuits, which changes the morphology and activity of microglia in the cerebral cortex. However, whether similar morphological changes can be observed in the spinal cord remains unclear. Therefore, we evaluated neuronal population activity in layer 5 (L5) of M1 following SCI and investigated whether changes in the activities of L5 neurons affect microglia-axon interactions using C57BL/6J mice. We discovered that L5 of the primary motor cortex (corticospinal neurons) exhibited reduced synchronized activity after SCI that correlates with microglial morphology, which was recovered using tDCS. This indicates that tDCS promotes changes in the morphological properties and recovery of microglia after SCI. Combining immunotherapy with tDCS may be effective in treating SCI.

    DOI: 10.1038/s41598-024-69127-7

    Open Access

    Scopus

    PubMed

  5. Glutamatergic signaling from melanin-concentrating hormone-producing neurons: A requirement for memory regulation, but not for metabolism control. International journal Open Access

    Xuan Thang Pham, Yoshifumi Abe, Yasutaka Mukai, Daisuke Ono, Kenji F Tanaka, Yu Ohmura, Hiroaki Wake, Akihiro Yamanaka

    PNAS nexus   Vol. 3 ( 7 ) page: pgae275   2024.7

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    Language:English   Publishing type:Research paper (scientific journal)  

    Melanin-concentrating hormone-producing neurons (MCH neurons), found mainly in the lateral hypothalamus and surrounding areas, play essential roles in various brain functions, including sleep and wakefulness, reward, metabolism, learning, and memory. These neurons coexpress several neurotransmitters and act as glutamatergic neurons. The contribution of glutamate from MCH neurons to memory- and metabolism-related functions has not been fully investigated. In a mouse model, we conditionally knocked out Slc17a6 gene, which encodes for vesicular glutamate transporter 2 (vGlut2), in the MCH neurons exclusively by using two different methods: the Cre recombinase/loxP system and in vivo genome editing using CRISPR/Cas9. Then, we evaluated several aspects of memory and measured metabolic rates using indirect calorimetry. We found that mice with MCH neuron-exclusive vGlut2 ablation had higher discrimination ratios between novel and familiar stimuli for novel object recognition, object location, and three-chamber tests. In contrast, there was no significant change in body weight, food intake, oxygen consumption, respiratory quotient, or locomotor activity. These findings suggest that glutamatergic signaling from MCH neurons is required to regulate memory, but its role in regulating metabolic rate is negligible.

    DOI: 10.1093/pnasnexus/pgae275

    Open Access

    Scopus

    PubMed

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MISC 15

  1. Psychiatric disorders and neuroinflammation: Approaching the multidirectional function of microglia

    竹田育子, 和氣弘明

    臨床精神医学   Vol. 53 ( 4 )   2024

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  2. Holographic measurement and manipulation of multicellular circuit dynamics

    和氣弘明, 和氣弘明, 加藤大輔, 竹田育子, 竹田育子

    実験医学   Vol. 42 ( 7 )   2024

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  3. 不動化における筋量制御のメカニズム

    平田 悠, 野村 和弘, 加藤 大輔, 橘 吉寿, 内山 奏, 細岡 哲也, 原 雄二, 安達 貴弘, 柴崎 貢志, 和氣 弘明, 小川 渉

    日本臨床分子医学会学術総会プログラム・抄録集   Vol. 58回   page: 56 - 56   2023.4

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    Language:Japanese   Publisher:日本臨床分子医学会  

  4. 不動化はPiezo1/KLF15経路を介して筋萎縮を促進する

    平田 悠, 野村 和弘, 加藤 大輔, 橘 吉寿, 内山 奏, 細岡 哲也, 原 雄二, 安達 貴弘, 柴崎 貢志, 和氣 弘明, 小川 渉

    糖尿病   Vol. 65 ( Suppl.1 ) page: S - 185   2022.4

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    Language:Japanese   Publisher:(一社)日本糖尿病学会  

  5. 不動化はPiezo1/KLF15経路を介して筋萎縮を促進する

    平田 悠, 野村 和弘, 加藤 大輔, 橘 吉寿, 内山 奏, 細岡 哲也, 原 雄二, 安達 貴弘, 柴崎 貢志, 和氣 弘明, 小川 渉

    糖尿病   Vol. 65 ( Suppl.1 ) page: S - 185   2022.4

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    Language:Japanese   Publisher:(一社)日本糖尿病学会  

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Presentations 87

  1. 2光子励起を用いたホログラフィック光刺激の現状:生体試料への適用を目指して

    SUGIO SHOUTA, TACHIBANA YOSHIHISA, WAKE HIROAKI

    CREST第2回シンポジウム  2018.12 

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    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:西尾  

  2. 2光子励起を用いたホログラフィック光刺激法の開発:現状と展望

    SUGIO SHOUTA, TACHIBANA YOSHIHISA, WAKE HIROAKI

    シグナル伝達医学研究展開センター若手道場  2019.1 

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    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:淡路  

  3. 2光子顕微鏡による生体イメージング

    Wake Hiroaki

    京都大学呼吸器内科  2017.9 

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    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:京都  

  4. 2光子顕微鏡による生体イメージング

    Wake Hiroaki

    京都大学セミナー  2017.8 

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    Language:Japanese   Presentation type:Public lecture, seminar, tutorial, course, or other speech  

    Venue:京都  

  5. A New Type of Microscopy for Light Stimulation and 3D Imaging; Invited International conference

    Xiangyu Quan, Manoj Kumar, MATOBA Osamu, Yasuhiro Awatsuji, Yoshio Hayasaki, Satoshi Hasegawa, WAKE Hiroaki, Mitsuhiro Morita

    International Workshop on Holography and Related Technologies 2018 (IWH2018)  2018.11  IWH2018

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    Language:English   Presentation type:Oral presentation (invited, special)  

    Venue:Suzhou; China;  

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KAKENHI (Grants-in-Aid for Scientific Research) 21

  1. 神経-免疫連関による感覚認知システムの統合的理解

    2022 - 2027

    科学技術振興機構  戦略的な研究開発の推進 戦略的創造研究推進事業 CREST 

    和氣 弘明

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    Authorship:Principal investigator 

    本研究では免疫系が感覚受容と相互作用する分子-回路メカニズムを末梢と中枢のレベルで明らかにし、その連関を捉える。まず末梢神経系における感覚-免疫連関を分子動態を中心に各発達段階で明らかにし、これをマウスで検証する。さらに、提案者らが開発したホログラフィック顕微鏡による感覚伝送を可能し、要素抽出を行う。

  2. Regulation of sensory modalities by microglia and their contribution to psychiatric diseases

    Grant number:21H02662  2021.4 - 2024.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    WAKE Hiroaki

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    Authorship:Principal investigator 

    Grant amount:\17550000 ( Direct Cost: \13500000 、 Indirect Cost:\4050000 )

    We have identified the contribution of microglia to heterogeneous sensory plasticity and examined their involvement in psychiatric disease pathology.First, we showed that there is a projection from each primary sensory cortex to V2L, a higher visual cortex, and examined the functional response of neurons in V2L. We found that the response of V2L is normally suppressed by mustache stimulation, but its activity frequency is enhanced by visual deprivation. Detailed examination revealed that microglia contribute to the acquisition of excitability of excitatory neurons by contacting the peri-excitatory neurons and stripping inhibitory synapses upon visual deprivation. We also found that this acquired excitability contributes to sensory discrimination of whiskers.

  3. Multi-layered study from the perspective of brain-immune system interactions to elucidate the pathophysiology of mental disorders.

    Grant number:21H04815  2021.4 - 2024.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (A)

    Ozaki Norio

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    Authorship:Coinvestigator(s) 

    We conducted a multi-layered study from the perspective of brain-immune system interactions, using patient-derived samples with identified genomic mutations and model cells and mice with the same variants, to elucidate the pathophysiology of mental disorders. Focusing particularly on the 22q11.2 deletion as a model for mental disorders, we obtained significant insights through the analysis of peripheral blood, gut microbiota, postmortem brains from patients with genomic variants, and iPScell-derived neurons, organoids, and microglia. These findings have been successfully documented in published papers.

  4. Effects of maternal undernutrition on offspring brain development via a newly discovered GABAergic CRH release pathway

    Grant number:21H02661  2021.4 - 2024.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    FUKUDA Atsuo

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    Authorship:Coinvestigator(s) 

    We demonstrated in an adult animal model that the GABAergic CRH release pathway (novel HPA axis) mediated by specific Cl- homeostasis is the glucocorticoid release pathway during undernutrition. The histological development of the HPA axis in fetuses was completed around postnatal day 0 for the conventional HPA axis, and the novel axis was delayed around postnatal day 7. The physiological development of the conventional HPA axis was identified using the GABA reversal potential and GABAergic IPSCs of CRH cells. A fetal undernutrition model was created by restricting maternal food intake during the late stages of pregnancy. We observed a decrease in maternal body weight and an increase in maternal and fetal blood corticosterone, suggesting that maternal malnutrition affects the Cl- homeostasis of fetal CRH cells, weakening the postnatal GABAergic inhibitory power and stimulating the HPA axis.

  5. Glia decoding: deciphering information critical for brain-body interactions

    Grant number:20H05894  2020.11 - 2025.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Transformative Research Areas (A)

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    Authorship:Coinvestigator(s) 

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Industrial property rights 3

  1. ホログラフィック3次元マルチスポット光刺激装置及び方法

    的場 修, 全 香玉, 和氣 弘明

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    Applicant:国立大学法人神戸大学

    Application no:JP2019027232  Date applied:2019.7

    Publication no:WO2020-013208  Date published:2020.1

    J-GLOBAL

  2. ホログラフィック3次元マルチスポット光刺激装置及び方法

    的場 修, 全 香玉, 和氣 弘明

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    Applicant:国立大学法人神戸大学

    Application no:JP2019027232  Date applied:2019.7

    Patent/Registration no:特許第7170342号  Date registered:2022.11 

    J-GLOBAL

  3. 透光性生体留置デバイス及びその利用

    平等 拓範, 佐藤 庸一, 鍋倉 淳一, 和氣 弘明

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    Applicant:大学共同利用機関法人自然科学研究機構

    Application no:特願2014-242148  Date applied:2014.11

    Announcement no:特開2016-101390  Date announced:2016.6

    Patent/Registration no:特許第6653096号  Date registered:2020.1 

    J-GLOBAL

 

Teaching Experience (On-campus) 1

  1. Neuro Anatomy

    2024

Teaching Experience (Off-campus) 17

  1. 文献解析・プレゼンテーション演習

    Kobe University)

  2. 神戸大学の研究最前線B

    Kobe University)

  3. 生理学

    Kobe University)

  4. 医学B

    Kobe University)

  5. 医学A

    Kobe University)

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