KADOWAKI Hisae

写真a

Affiliation

Faculty of Medicine School of Medicine Department of Medical Sciences, Biochemistry and Molecular Biology

Title

Assistant Professor

External Link

Degree 【 display / non-display

  • 博士(学術) ( 2005.3   東京医科歯科大学 )

Research Areas 【 display / non-display

  • Life Science / Oral pathobiological science

  • Life Science / Cell biology

 

Papers 【 display / non-display

  • Chemical chaperones ameliorate neurodegenerative disorders in Derlin-1-deficient mice via improvement of cholesterol biosynthesis Reviewed

    Sugiyama T., Murao N., Kadowaki H., Nishitoh H.

    Scientific Reports   12 ( 1 )   21840   2022.12

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Scientific Reports  

    There are no available therapies targeting the underlying molecular mechanisms of neurodegenerative diseases. Although chaperone therapies that alleviate endoplasmic reticulum (ER) stress recently showed promise in the treatment of neurodegenerative diseases, the detailed mechanisms remain unclear. We previously reported that mice with central nervous system-specific deletion of Derlin-1, which encodes an essential component for ER quality control, are useful as models of neurodegenerative diseases such as spinocerebellar degeneration. Cholesterol biosynthesis is essential for brain development, and its disruption inhibits neurite outgrowth, causing brain atrophy. In this study, we report a novel mechanism by which chemical chaperones ameliorate brain atrophy and motor dysfunction. ER stress was induced in the cerebella of Derlin-1 deficiency mice, whereas the administration of a chemical chaperone did not alleviate ER stress. However, chemical chaperone treatment ameliorated cholesterol biosynthesis impairment through SREBP-2 activation and simultaneously relieved brain atrophy and motor dysfunction. Altogether, these findings demonstrate that ER stress may not be the target of action of chaperone therapies and that chemical chaperone-mediated improvement of brain cholesterol biosynthesis is a promising novel therapeutic strategy for neurodegenerative diseases.

    DOI: 10.1038/s41598-022-26370-0

    Scopus

    PubMed

  • Molecular mechanism of thermogenesis via ER-mitochondrial crosstalk signaling in brown adipose tissue

    Kadowaki Hisae, Nishitoh Hideki

    94 ( 1 )   97 - 101   2022.2

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

    DOI: 10.14952/seikagaku.2022.940097

    Scopus

    CiNii Research

  • ERAD components Derlin-1 and Derlin-2 are essential for postnatal brain development and motor function Reviewed

    Takashi Sugiyama, Naoya Murao, Hisae Kadowaki, Keizo Takao, Tsuyoshi Miyakawa, Yosuke Matsushita, Toyomasa Katagiri, Akira Futatsugi, Yohei Shinmyo, Hiroshi Kawasaki, Juro Sakai, Kazutaka Shiomi, Masamitsu Nakazato, Kohsuke Takeda, Katsuhiko Mikoshiba, Hidde L. Ploegh, Hidenori Ichijo, Hideki Nishitoh

    iScience   24 ( 7 )   102758 - 102758   2021.7

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.isci.2021.102758

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  • ER-resident sensor PERK is essential for mitochondrial thermogenesis in brown adipose tissue. Reviewed International journal

    Hironori Kato, Kohki Okabe, Masato Miyake, Kazuki Hattori, Tomohiro Fukaya, Kousuke Tanimoto, Shi Beini, Mariko Mizuguchi, Satoru Torii, Satoko Arakawa, Masaya Ono, Yusuke Saito, Takashi Sugiyama, Takashi Funatsu, Katsuaki Sato, Shigeomi Shimizu, Seiichi Oyadomari, Hidenori Ichijo, Hisae Kadowaki, Hideki Nishitoh

    Life science alliance   3 ( 3 )   2020.3

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

    Mitochondria play a central role in the function of brown adipocytes (BAs). Although mitochondrial biogenesis, which is indispensable for thermogenesis, is regulated by coordination between nuclear DNA transcription and mitochondrial DNA transcription, the molecular mechanisms of mitochondrial development during BA differentiation are largely unknown. Here, we show the importance of the ER-resident sensor PKR-like ER kinase (PERK) in the mitochondrial thermogenesis of brown adipose tissue. During BA differentiation, PERK is physiologically phosphorylated independently of the ER stress. This PERK phosphorylation induces transcriptional activation by GA-binding protein transcription factor α subunit (GABPα), which is required for mitochondrial inner membrane protein biogenesis, and this novel role of PERK is involved in maintaining the body temperatures of mice during cold exposure. Our findings demonstrate that mitochondrial development regulated by the PERK-GABPα axis is indispensable for thermogenesis in brown adipose tissue.

    DOI: 10.26508/lsa.201900576

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  • Endoplasmic reticulum quality control by garbage disposal Invited Reviewed

    Kadowaki H., Nishitoh H.

    The FEBS journal   286 ( 2 )   232 - 240   2019.1

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:FEBS Journal  

    © 2018 Federation of European Biochemical Societies Various types of intracellular and extracellular stresses disturb homeostasis in the endoplasmic reticulum (ER) and, thus, trigger the ER stress response. Unavoidable and/or prolonged ER stress causes cell toxicity and occasionally cell death. The malfunction or death of irreplaceable cells leads to conformational diseases, including diabetes mellitus, ischemic diseases, metabolic diseases, and neurodegenerative diseases. In the past several decades, many studies have revealed the molecular mechanisms of the ER quality control system. Cells resolve ER stress by promptly and accurately reducing the amount of malfolded proteins. Recent reports have revealed that cells possess several types of ER-related disposal systems, including mRNA decay, proteasomal degradation, and autophagy. The removal of dispensable RNAs, proteins, and organelle parts may enable the effective maintenance of a functional ER. Here, we provide a comprehensive understanding of the ER quality control system by focusing on ER-related garbage disposal systems.

    DOI: 10.1111/febs.14589

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    PubMed

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Books 【 display / non-display

  • 褐色脂肪組織における小胞体-ミトコンドリア間クロストークシグナルを介した熱産生

    門脇寿枝、西頭英起( Role: Joint author)

    公益社団法人日本生化学会  2022.2 

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    Language:Japanese Book type:Scholarly book

    DOI: 10.14952/SEIKAGAKU.2022.940097

  • アポトーシス. 「キーワード:蛋白質の一生」

    門脇寿枝, 西頭英起( Role: Joint author)

    共立出版  2008.6 

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    Language:Japanese Book type:Scholarly book

  • 異常タンパク質が発信する神経細胞死シグナル伝達

    門脇寿枝, 西頭英起, 一條秀憲( Role: Joint author)

    実験医学  2006.6 

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    Language:Japanese Book type:Scholarly book

  • アミロイドβ誘導性神経細胞死の分子メカニズム

    門脇寿枝, 西頭英起( Role: Joint author)

    Cognition and Dementia  2004.10 

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    Language:Japanese Book type:Scholarly book

  • アポトーシスとシグナル伝達

    門脇寿枝, 西頭英起, 一條秀憲( Role: Sole author)

    現代医療  2003 

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    Language:Japanese Book type:Scholarly book

MISC 【 display / non-display

  • Signaling Pathways from the Endoplasmic Reticulum and their Role in Diseases.

    Kadowaki H., Nishitoh H.

    Genes   4 ( 3 )   306 - 333   2013.7

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    Language:English   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)   Publisher: MDPI AG  

    DOI: 10.3390/genes4030306

Presentations 【 display / non-display

  • Regulatory mechanism of stress-dependent cotranslational degradation on the ER membrane Invited

    Hisae Kadowaki

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    Event date: 2022.11.9 - 2022.11.11

    Language:English   Presentation type:Symposium, workshop panel (public)  

  • 小胞体膜上での翻訳分解の制御機構

    門脇寿枝

    第15回小胞体ストレス研究会  2022.7.31 

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    Event date: 2022.7.30 - 2022.7.31

    Language:Japanese   Presentation type:Oral presentation (general)  

  • 小胞体膜上での翻訳時分解の制御機構 Invited

    門脇寿枝, 西頭英起

    第44回日本分子生物学会年会  2021.12.3 

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    Event date: 2021.12.1 - 2021.12.3

    Presentation type:Symposium, workshop panel (public)  

  • 小胞体の予防的品質管理における新生タンパク質の翻訳制御

    門脇寿枝, 西頭英起

    第15回日本臨床ストレス応答学会大会  2021.11.20 

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    Event date: 2021.11.19 - 2021.11.20

    Presentation type:Oral presentation (general)  

  • 小胞体の予防的品質管理における新規合成タンパク質の翻訳制御機構

    門脇寿枝, 西頭英起

    第73回日本細胞生物学会大会  2021.7.2 

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    Event date: 2021.6.29 - 2021.7.2

    Presentation type:Oral presentation (general)  

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Awards 【 display / non-display

  • 宮崎大学女性研究者奨励賞

    2017.3   宮崎大学  

    門脇寿枝

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    Country:Japan

  • 第39回日本分子生物学会年会優秀ポスター賞

    2016.11   日本分子生物学会  

    門脇寿枝

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    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

  • 第11回小胞体ストレス研究会ポスター大賞

    2016.10   小胞体ストレス研究会  

    門脇寿枝

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    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

  • 若手研究奨励賞

    2012.11   臨床ストレス応答学会  

    門脇寿枝

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    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

Grant-in-Aid for Scientific Research 【 display / non-display

  • 小胞体ストレスにおける予防的品質管理の分子機構の解明

    Grant number:21K06175  2021.04 - 2024.03

    独立行政法人日本学術振興会  科学研究費補助金  基盤研究(C)

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    Authorship:Principal investigator 

  • 小胞体ストレスによる新規合成タンパク質の分解機構の解明

    2018.04 - 2021.03

    科学研究費補助金  基盤研究(C)

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    Authorship:Principal investigator 

  • 口腔領域マクロファージにおける小胞体ストレスシグナルを介した炎症病態機構の解明

    2015.04 - 2018.03

    科学研究費補助金  基盤研究(C)

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    Authorship:Principal investigator 

    口腔内は常に創傷・温熱刺激・細菌・ウィルス感染・異物接触などのストレスに曝されており、難治性の口腔粘膜炎症を引き起こすことが多い。このような口腔内の慢性炎症は、ときとして口腔前がん病変(白板症・紅板症・扁平苔癬)、さらには発がんの原因になることもあり、その病態メカニズムを明らかにすることは重要である。最近の研究により、様々な炎症性疾患に共通に認められる組織、細胞内現象として、小胞体ストレスが注目されている。そこで本研究では、in vitroおよびin vivo炎症モデル実験系を用いて、炎症病態に関わる主要な細胞の一つであるマクロファージの分化・活性化・アポトーシスの分子機構を、小胞体ストレスシグナルの観点から解明し、炎症性疾患の克服に繋げることを目的とする。

  • 口腔領域がん克服のための小胞体ストレス応答の役割の解明

    2013.04 - 2015.03

    科学研究費補助金  若手研究(B)

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     本研究の対象とするがん細胞においては、小胞体ストレス誘導性アポトーシスが抑制され、逆に小胞体ストレス応答(UPR: Unfolded protein response)を介した生存・増殖シグナルが増強されていることが予想される。これまでの研究により、この小胞体ストレス誘導性アポトーシスシグナルの実行因子としてASK1 を同定し詳細な機能解析を行ってきた。一方、UPRの一つ小胞体関連分解(ERAD: ER-associated degradation)のメカニズムとその破綻による細胞死分子機構についても明らかにしてきた。これらの小胞体ストレスによる細胞の生と死に関する研究基盤を踏まえ、本研究では口腔がんにおける小胞体ストレスシグナルの関与を明らかにし、新たな口腔がん創薬標的に迫る。

  • 口腔領域がん克服のための小胞体ストレス応答の役割の解明

    2013.04 - 2015.03

    科学研究費補助金  若手研究(B)

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    Authorship:Principal investigator 

    口腔領域がん克服のための小胞体ストレス応答の役割の解明