Updated on 2021/11/02

写真a

 
DOURA Tomohiro
 
Organization
Graduate School of Engineering Biomolecular Engineering 2 Assistant Professor
Graduate School
Graduate School of Engineering
Undergraduate School
School of Engineering Chemistry and Biotechnology
Title
Assistant Professor

Degree 1

  1. 博士(工学) ( 2012.3   九州大学 ) 

Research Interests 6

  1. neuroscience

  2. molecular biology

  3. chemical biology

  4. chemical genetics

  5. medicinal chemistry

  6. chemical biology

Research Areas 2

  1. Nanotechnology/Materials / Bio chemistry

  2. Life Science / Pharmaceutical chemistry and drug development sciences

Current Research Project and SDGs 1

  1. Chemical genetics research for neurotransmitter receptors

Research History 4

  1. Nagoya University   Graduate School of Engineering Biomolecular Engineering   Assistant Professor

    2020.10

  2. 名古屋大学大学院工学研究科 生命分子工学専攻   化学遺伝学研究グループ   特任助教

    2019.6 - 2020.9

  3. Tokyo University of Pharmacy and Life Sciences

    2018.7 - 2019.5

  4. Yamaguchi University   Assistant Professor

    2016.10 - 2018.6

Professional Memberships 5

  1. 日本化学会

  2. 日本薬学会

  3. THE PHARMACEUTICAL SOCIETY OF JAPAN

  4. THE CHEMICAL SOCIETY OF JAPAN

  5. JAPANESE SOCIETY FOR CHEMICAL BIOLOGY

 

Papers 18

  1. Tethering-based chemogenetic approaches for the modulation of protein function in live cells Reviewed International coauthorship International journal

    Yu-Hsuan Tsai, Tomohiro Doura, Shigeki Kiyonaka

    Chemical Society Reviews   Vol. 50 ( 14 ) page: 7909 - 7923   2021.7

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Royal Society of Chemistry (RSC)  

    <p>Approaches for selective and rapid modulation are ideal for investigating the physiological roles of proteins. This review focuses on chemogenetic approaches in which designer molecules are attached to the target protein for the modulation of proteins in live cells.</p>

    DOI: 10.1039/d1cs00059d

    Web of Science

    Scopus

    PubMed

  2. Ligand-directed two-step labeling to quantify neuronal glutamate receptor trafficking Reviewed International journal

    Kento Ojima, Kazuki Shiraiwa, Kyohei Soga, Tomohiro Doura, Mikiko Takato, Kazuhiro Komatsu, Michisuke Yuzaki, Itaru Hamachi, Shigeki Kiyonaka

    Nature Communications   Vol. 12 ( 1 ) page: 831   2021.2

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

    <title>Abstract</title>The regulation of glutamate receptor localization is critical for development and synaptic plasticity in the central nervous system. Conventional biochemical and molecular biological approaches have been widely used to analyze glutamate receptor trafficking, especially for α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate-type glutamate receptors (AMPARs). However, conflicting findings have been reported because of a lack of useful tools for analyzing endogenous AMPARs. Here, we develop a method for the rapid and selective labeling of AMPARs with chemical probes, by combining affinity-based protein labeling and bioorthogonal click chemistry under physiological temperature in culture medium. This method allows us to quantify AMPAR distribution and trafficking, which reveals some unique features of AMPARs, such as a long lifetime and a rapid recycling in neurons. This method is also successfully expanded to selectively label <italic>N</italic>-methyl-D-aspartate-type glutamate receptors. Thus, bioorthogonal two-step labeling may be a versatile tool for investigating the physiological and pathophysiological roles of glutamate receptors in neurons.

    DOI: 10.1038/s41467-021-21082-x

    Web of Science

    Scopus

    PubMed

    Other Link: http://www.nature.com/articles/s41467-021-21082-x

  3. Selective acetylcholinesterase inhibitors derived from muscle relaxant dantrolene Reviewed International journal

    Aoyama Hiroshi, Doura Tomohiro

    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS   Vol. 30 ( 4 ) page: 126888   2020.2

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    Authorship:Last author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Bioorganic and Medicinal Chemistry Letters  

    Dantrolene, the only therapeutic agent for malignant hyperthermia, is known to have not only a muscle relaxant effect, but also a neuroprotective effect and Alzheimer's disease improving effect. Recently, it has been reported that dantrolene has a weak inhibitory effect on acetylcholinesterase (AChE), which is a therapeutic drug target for Alzheimer's disease. Thus, we focused on developing of AChE inhibitors with benzylpiperidine/piperazine moieties that are based on the dantrolene skeleton. Several derivatives showed an inhibitory activity. Among them, ortho-nitro derivative 8c showed the most potent inhibitory activity with the IC50 value of 34.2 nM. Furthermore, Lineweaver-Burk plot analysis indicated that 8c is AChE-selective inhibitor, which shows only a weak inhibitory effect on butyrylcholinesterase (BuChE) and a non-competitive inhibition.

    DOI: 10.1016/j.bmcl.2019.126888

    Web of Science

    Scopus

    PubMed

  4. Selective acetylcholinesterase inhibitors derived from muscle relaxant dantrolene Reviewed

    Hiroshi Aoyama, Tomohiro Doura

    Bioorganic and Medicinal Chemistry Letters   Vol. 30 ( 4 ) page: 126888   2020.2

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

  5. 内在性のGタンパク質共役型受容体を光によって制御する Invited Reviewed

    堂浦 智裕

    ファルマシア   Vol. 56 ( 5 ) page: 441 - 441   2020

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    Authorship:Lead author, Last author, Corresponding author   Language:Japanese   Publishing type:Part of collection (book)   Publisher:公益社団法人 日本薬学会  

    生体中には800種類以上のGタンパク質共役型受容体(GPCRs)が存在している.個々のGPCRの生物学的・病理学的機能を解明することは生命機能や病態の理解,治療法の開発に結びつくため重要である.代表的なGPCRの化学遺伝学的活性制御法はdesigner receptors exclusively activated by designer drugs(DREADDs)であるが,本手法で使用されるムスカリン受容体は人工リガンドにのみ結合するように改変されているため,本来の機能を喪失している.<br>そこで,標的GPCRの機能を維持したままGPCRの機能を解明する化学遺伝学的手法として,Broichhagen J.らは光刺激によってGPCRの活性を制御するphotoswitchable orthogonal remotely tethered ligand(PORTL)を開発した.細胞表層にSNAP-tag融合代謝型グルタミン酸受容体2(SNAP-mGluR2)を発現させ,mGluR2の天然アゴニストであるグルタミン酸・光スイッチ部位・SNAP-tag基質を適切なリンカーで連結した分子(BGAG)でラベル化して作製したPORTL(SNAG-mGluR2)に光照射することによりSNAG-mGluR2の活性制御に成功している.しかし,PORTLは原理的に内在性GPCRの活性を制御できない.<br>本稿では, Donthamsetti P. C.らが開発した内在性GPCRの活性を光制御可能なPORTLの発展型であるmaPORTLについて紹介する.<br>なお,本稿は下記の文献に基づいて,その研究成果を紹介するものである.<br>1) Urban D. J. <i>et</i> <i>al</i>., <i>Annu</i>. <i>Rev</i>. <i>Pharmacol</i>. <i>Toxicol</i>., <b>55</b>, 399-417(2015).<br>2) Broichhagen J. <i>et</i> <i>al</i>., <i>ACS</i> <i>Cent</i>. <i>Sci</i>., <b>1</b>, 383-393(2015).<br>3) Donthamsetti P. C. <i>et</i> <i>al</i>., <i>J</i>. <i>Am</i>. <i>Chem</i>. <i>Soc</i>., <b>141</b>, 11522-11530(2019).

    DOI: 10.14894/faruawpsj.56.5_441

    CiNii Article

  6. Relationship between the glutathione-responsive degradability of thiol-organosilica nanoparticles and the chemical structures Reviewed International coauthorship

    T. Doura, T. Nishio, F. Tamanoi, M. Nakamura

    J. Mater. Res.   Vol. 34 ( 7 ) page: 1266 - 1278   2019.2

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  7. Biodegradability of disulfide-organosilica nanoparticles evaluated by soft X-ray photoelectron spectroscopy: cancer therapy implications Reviewed

    H. Mekaru, A. Yoshigoe, M. Nakamura, T. Doura, F. Tamanoi

    ACS Appl. Nano Mater.   Vol. 2 ( 1 ) page: 479 - 488   2018.12

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

  8. Miniaturization of thiol-organosilica nanoparticles induced by an anionic surfactant Reviewed International coauthorship

    Tomohiro Doura, Fuyuhiko Tamanoi, Michihiro Nakamura

    Journal of Colloid and Interface Science   Vol. 526   page: 51 - 62   2018.9

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Academic Press Inc.  

    Thiol-organosilica nanoparticles are a promising nanomaterial for biomedical applications. The enhanced permeability and retention (EPR) effect is useful for tumor targeting within the biomedical applications of nanomaterials, and nanomaterials with a size of less than 200 nm exhibit the maximum EPR effect. However, the synthesis of thiol-organosilica nanoparticles with a diameter of less than 200 nm is not efficient for the yield using the present conventional synthetic methods. Herein, we report the development of an efficient synthetic method of thiol-organosilica nanoparticles with a diameter of less than 200 nm using an anionic surfactant and discuss its mechanism. Compared with the conventional synthetic methods, a greater than 10-fold miniaturization of thiol-organosilica nanoparticles and an approximately 40-fold increase in the production efficiency of small thiol-organosilica nanoparticles were achieved using the sodium dodecyl sulfate (SDS)-addition synthetic method or sodium dodecylbenzenesulfonate (SDBS)-addition synthetic method. This is the first report about the miniaturization of organosilica nanoparticles induced by an anionic surfactant. The SDS-addition synthetic method or SDBS-addition synthetic method will accelerate the biomedical applications of thiol-organosilica nanoparticles.

    DOI: 10.1016/j.jcis.2018.04.090

    Scopus

  9. Hybrid cell reactor system from Escherichia coli protoplast cells and arrayed lipid bilayer chamber device Reviewed

    Y. Moriizumi, K. V. Tabata, R. Watanabe, T. Doura, M. Kamiya, Y. Urano, H. Noji

    Sci. Rep.   Vol. 8 ( 1 ) page: 11757   2018.8

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

  10. Combretastatin A4-beta-galactosyl conjugates for ovarian cancer prodrug monotherapy Reviewed

    T. Doura, K. Takahashi, Y. Ogura, N. Suzuki

    ACS Med. Chem. Lett.   Vol. 8 ( 2 ) page: 211 - 214   2017.1

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

  11. Detection of lacZ-positive cells in living tissue with single-cell resolution. Reviewed International journal

    T. Doura, M. Kamiya, F. Obata, Y. Yamaguchi, T. Y. Hiyama, T. Matsuda, A. Fukamizu, M. Noda, M. Miura, Y. Urano.

    Angew. Chem., Int. Ed.   Vol. 55   page: 9620 - 9624   2016.7

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  12. PAMAM dendron lipid assemblies that undergo structural transition in response to weakly acidic pH and their cytoplasmic delivery capability. Reviewed

    T. Doura, M. Yamada, R. Teranishi, Y. Yamamoto, T. Sugimoto, E. Yuba, A. Harada, K. Kono.

    Langmuir   Vol. 31   page: 5105 - 5114   2015.4

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  13. Phenylboronic acid-based 19F MRI probe for the detection and imaging of hydrogen peroxide utilizing its large chemical-shift change. Reviewed

    H. Nonaka, Q. An, F. Sugihara, T. Doura, A. Tsuchiya, Y. Yoshioka, S. Sando.

    Anal. Sci.   Vol. 31 ( 4 ) page: 331 - 335   2015.4

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

  14. An adhesive 19F MRI chemical probe allows signal off-to-on-type molecular sensing in a biological environment. Reviewed

    T. Doura, R. Hata, H. Nonaka, F. Sugihara, Y. Yoshioka, S. Sando.

    Chem. Commun.   Vol. 49   page: 11421 - 11423   2013.10

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  15. A platform for designing hyperpolarized magnetic resonance chemical probes. Reviewed

    H. Nonaka, R. Hata, T. Doura, T. Nishihara, K. Kumagai, M. Akakabe, M. Tsuda, K. Ichikawa, S. Sando.

    Nat. Commun.   Vol. 4   page: 2411   2013.9

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

  16. Design of a 13C magnetic resonance probe using a deuterated methoxy group as a long-lived hyperpolarization unit. Reviewed

    T. Doura, R. Hata, H. Nonaka, K. Ichikawa, S. Sando.

    Angew. Chem., Int. Ed.   Vol. 51 ( 40 ) page: 10114 - 10117   2012.9

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  17. p-Aminophenyl alkyl ether-based 19F MRI probe for specific detection and imaging of hypochlorite ion. Reviewed

    T. Doura, Q. An, F. Sugihara, T. Matsuda, S. Sando.

    Chem. Lett.   Vol. 40 ( 12 ) page: 1357 - 1359   2011.11

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  18. Atom arrangement strategy for designing a turn-on 1H magnetic resonance probe: a dual activatable probe for multimodal detection of hypochlorite. Reviewed

    T. Doura, H. Nonaka, S. Sando.

    Chem. Commun.   Vol. 48   page: 1565 - 1567   2011.5

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

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Books 1

  1. 実験医学2016年12月号 Vol.34 No.19 pp.3197-3201、クローズアップ実験法:生体組織中のlacZ発現細胞のライブ蛍光検出

    堂浦智裕、神谷真子、浦野泰照( Role: Sole author ,  全般)

    羊土社  2016.11  ( ISBN:978-4-7581-0158-5

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    Total pages:5   Language:Japanese Book type:Scholarly book

MISC 13

  1. Relationship between the glutathione-responsive degradability of thiol-organosilica nanoparticles and the chemical structures Reviewed

    T. Doura, T. Nishio, F. Tamanoi, M. Nakamura

    J. Mater. Res.   Vol. 34 ( 7 ) page: 1266-1278   2019.2

     More details

    Language:English  

  2. Biodegradability of disulfide-organosilica nanoparticles evaluated by soft X-ray photoelectron spectroscopy: cancer therapy implications Reviewed

    H. Mekaru, A. Yoshigoe, M. Nakamura, T. Doura, F. Tamanoi

    ACS Appl. Nano Mater.   Vol. 2 ( 1 ) page: 479-488   2018.12

     More details

    Language:English  

  3. Miniaturization of thiol-organosilica nanoparticles induced by an anionic surfactant Reviewed

    T. Doura, F. Tamanoi, M. Nakamura

    J. Colloid Interface Sci.   Vol. 526   page: 51-62   2018.9

  4. Hybrid cell reactor system from Escherichia coli protoplast cells and arrayed lipid bilayer chamber device Reviewed

    Y. Moriizumi, K. V. Tabata, R. Watanabe, T. Doura, M. Kamiya, Y. Urano, H. Noji

    Sci. Rep.   Vol. 8 ( 1 ) page: 11757   2018.8

     More details

    Language:English  

  5. Combretastatin A4-beta-galactosyl conjugates for ovarian cancer prodrug monotherapy Reviewed

    T. Doura, K. Takahashi, Y. Ogura, N. Suzuki

    ACS Med. Chem. Lett.   Vol. 8 ( 2 ) page: 211-214   2017.2

     More details

    Language:English  

  6. Detection of lacZ-positive cells in living tissue with single-cell resolution Reviewed

    T. Doura, M. Kamiya, F. Obata, Y. Yamaguchi, T. Y. Hiyama, T. Matsuda, A. Fukamizu, M. Noda, M. Miura, Y. Urano

    Angew. Chem. Int. Ed.   Vol. 55 ( 33 ) page: 9620-9624   2016.8

     More details

    Language:English  

    DOI: 10.1002/anie.201603328

  7. PAMAM dendron lipid assemblies that undergo structural transition in response to weakly acidic pH and their cytoplasmic delivery capability Reviewed

    T. Doura, M. Yamada, R. Teranishi, Y. Yamamoto, T. Sugimoto, E. Yuba, A. Harada, K. Kono

    Langmuir   Vol. 31 ( 18 ) page: 5105-5114   2015.4

     More details

    Language:English  

    DOI: 10.1021/acs.langmuir.5b00183

  8. Phenylboronic acid-based 19F MRI probe for the detection and imaging of hydrogen peroxide utilizing its large chemical-shift change Reviewed

    H. Nonaka, Q. An, F. Sugihara, T. Doura, A. Tsuchiya, Y. Yoshioka, S. Sando

    Anal. Sci.   Vol. 31 ( 4 ) page: 331-335   2015.4

     More details

    Language:English  

    DOI: 10.2116/analsci.31.331

  9. A platform for designing hyperpolarized magnetic resonance chemical probes Reviewed

    H. Nonaka, R. Hata, T. Doura, T. Nishihara, K. Kumagai, M. Akakabe, M. Tsuda, K. Ichikawa, S. Sando

    Nat. Commun.   Vol. 4   page: 2411   2013.12

     More details

    Language:English  

    DOI: 10.1038/ncomms3411

  10. An adhesive 19F MRI chemical probe allows signal off-to-on-type molecular sensing in a biological environment Reviewed

    T. Doura, R. Hata, H. Nonaka, F. Sugihara, Y. Yoshioka, S. Sando

    Chem. Commun.   Vol. 49 ( 97 ) page: 11421-11423   2013.12

     More details

    Language:English  

    DOI: 10.1039/c3cc46471g

  11. Design of a 13C magnetic resonance probe using a deuterated methoxy group as a long-lived hyperpolarization unit Reviewed

    T. Doura, R. Hata, H. Nonaka, K. Ichikawa, S. Sando

    Angew. Chem. Int. Ed.   Vol. 51 ( 40 ) page: 10114-10117   2012.10

     More details

    Language:English  

    DOI: 10.1002/anie.201202885

  12. Atom arrangement strategy for designing a turn-on 1H magnetic resonance probe: a dual activatable probe for multimodal detection of hypochlorite Reviewed

    T. Doura, H. Nonaka, S. Sando

    Chem. Commun.   Vol. 48 ( 10 ) page: 1565-1567   2012.2

     More details

    Language:English  

    DOI: 10.1039/c1cc12044a

  13. p-Aminophenyl alkyl ether-based 19F MRI probe for specific detection and imaging of hypochlorite ion Reviewed

    T. Doura, Q. An, F. Sugihara, T. Matsuda, S. Sando

    Chem. Lett.   Vol. 40 ( 12 ) page: 1357-1359   2011.12

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    Language:English  

    DOI: 10.1246/cl.2011.1357

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Research Project for Joint Research, Competitive Funding, etc. 1

  1. beta-ガラクトシダーゼ活性により機能発現するヘキストを基盤とするアルキル化剤の開発

    2015.12 - 2016.11

    持田記念医学薬学振興財団 平成27年度 研究助成金 

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    Grant type:Competitive

KAKENHI (Grants-in-Aid for Scientific Research) 4

  1. がん選択的化学療法の実現を目指した細胞内滞留型プロドラッグの開発

    2016.4 - 2019.3

    日本学術振興会  科学研究費 若手研究B 

    堂浦 智裕

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    Authorship:Principal investigator  Grant type:Competitive

  2. Development of sunitinib-based molecular targeted drug conjugates

    Grant number:19K16325  2019.4 - 2022.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Early-Career Scientists  Grant-in-Aid for Early-Career Scientists

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    Authorship:Principal investigator 

    Grant amount:\2860000 ( Direct Cost: \2200000 、 Indirect Cost:\660000 )

  3. がん選択的化学療法の実現を目指した細胞内滞留型プロドラッグの開発

    2016.4 - 2019.3

    科学研究費補助金  若手研究(B)

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    Authorship:Principal investigator 

  4. Development of anti-tumor prodrugs accumulating in tumor cells for tumor-selective chemotherapy

    Grant number:16K18909  2016.4 - 2019.3

    Doura Tomohiro

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\4290000 ( Direct Cost: \3300000 、 Indirect Cost:\990000 )

    I have my sights on the development of “Magic Bullet” for cancer tissues. I achieved 1) the development of a beta-galactosidase targeting prodrug candidate for ovarian cancer and 2) the development of glutathione-responsive degradable thiol-organosilica nanoparticles as a potential drug carrier for cancer tissues. I think that these accomplishments contribute the realization of selective chemotherapy for cancer tissues.