写真a

TAKAHASHI Shuntaro

Position

Associate Professor

Research Field

Bio-related chemistry

Graduating School 【 display / non-display

  •  
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    2002.03

    Tokyo Institute of Technology   Faculty of Life Science and Engineering   Graduated

Graduate School 【 display / non-display

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    2007.03

    Tokyo Institute of Technology  Graduate School, Division of Life Science and Engineering  Doctor's Course  Completed

Campus Career 【 display / non-display

  • 2012.06
    -
    Now

    KONAN UNIVERSITYFrontier of Institute for Biomolecular Engineering Research in Science and Technology Department of Nanobiochemistry   Lecturer  

 

Published Papers 【 display / non-display

  • Effect of Molecular Crowding on the Stability of RNA G-Quadruplexes with Various Numbers of Quartets and Lengths of Loops.

    Saki Matsumoto, Hisae Tateishi-Karimata, Shuntaro Takahashi, Tatsuya Ohyama, Naoki Sugimoto

    Biochemistry   59 ( 28 ) 2640 - 2649   2020.07

    Joint Work

    G-Quadruplexes are noncanonical structures formed by guanine-rich regions of not only DNA but also RNA. RNA G-quadruplexes are widely present in the transcriptome as mRNAs and noncoding RNAs and take part in various essential functions in cells. Furthermore, stable RNA G-quadruplexes control the extent of biological functions, such as mRNA translation and antigen presentation. To understand and regulate the functions controlled by RNA G-quadruplexes in cellular environments, which are molecularly crowded, we would be required to investigate the stability of G-quadruplexes in molecular crowding. Here, we systematically investigated the thermodynamic stability of RNA G-quadruplexes with different numbers of G-quartets and lengths of loops. The molecular crowding conditions of polyethylene glycol with an average molecular weight of 200 (PEG200) were found to stabilize RNA G-quadruplexes with three and four G-quartets, while G-quadruplexes with two G-quartets did not exhibit any stabilization upon addition of PEG200. On the other hand, no difference in stabilization by PEG200 was observed among the G-quadruplexes with different loop lengths. Thermodynamic analysis of the RNA G-quadruplexes revealed more appropriate motifs for identifying G-quadruplex-forming sequences. The informatics analysis with new motifs demonstrated that the distributions of G-quadruplexes in human noncoding RNAs differed depending on the number of G-quartets. Therefore, RNA G-quadruplexes with different numbers of G-quartets may play different roles in response to environmental changes in cells.

    DOI PubMed

  • Improved nearest-neighbor parameters for the stability of RNA/DNA hybrids under a physiological condition.

    Dipanwita Banerjee, Hisae Tateishi-Karimata, Tatsuya Ohyama, Saptarshi Ghosh, Tamaki Endoh, Shuntaro Takahashi, Naoki Sugimoto

    Nucleic acids research     2020.07

    Joint Work

    The stability of Watson-Crick paired RNA/DNA hybrids is important for designing optimal oligonucleotides for ASO (Antisense Oligonucleotide) and CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas9 techniques. Previous nearest-neighbour (NN) parameters for predicting hybrid stability in a 1 M NaCl solution, however, may not be applicable for predicting stability at salt concentrations closer to physiological condition (e.g. ∼100 mM Na+ or K+ in the presence or absence of Mg2+). Herein, we report measured thermodynamic parameters of 38 RNA/DNA hybrids at 100 mM NaCl and derive new NN parameters to predict duplex stability. Predicted ΔG°37 and Tm values based on the established NN parameters agreed well with the measured values with 2.9% and 1.1°C deviations, respectively. The new results can also be used to make precise predictions for duplexes formed in 100 mM KCl or 100 mM NaCl in the presence of 1 mM Mg2+, which can mimic an intracellular and extracellular salt condition, respectively. Comparisons of the predicted thermodynamic parameters with published data using ASO and CRISPR-Cas9 may allow designing shorter oligonucleotides for these techniques that will diminish the probability of non-specific binding and also improve the efficiency of target gene regulation.

    DOI PubMed

  • Nearest-neighbor parameters for predicting DNA duplex stability in diverse molecular crowding conditions.

    Saptarshi Ghosh, Shuntaro Takahashi, Tatsuya Ohyama, Tamaki Endoh, Hisae Tateishi-Karimata, Naoki Sugimoto

    Proceedings of the National Academy of Sciences of the United States of America     2020.06

    Joint Work

    The intracellular environment is crowded and heterogeneous. Although the thermodynamic stability of nucleic acid duplexes is predictable in dilute solutions, methods of predicting such stability under specific intracellular conditions are not yet available. We recently showed that the nearest-neighbor model for self-complementary DNA is valid under molecular crowding condition of 40% polyethylene glycol with an average molecular weight of 200 (PEG 200) in 100 mM NaCl. Here, we determined nearest-neighbor parameters for DNA duplex formation under the same crowding condition to predict the thermodynamics of DNA duplexes in the intracellular environment. Preferential hydration of the nucleotides was found to be the key factor for nearest-neighbor parameters in the crowding condition. The determined parameters were shown to predict the thermodynamic parameters (∆H°, ∆S°, and ∆G°37) and melting temperatures (Tm) of the DNA duplexes in the crowding condition with significant accuracy. Moreover, we proposed a general method for predicting the stability of short DNA duplexes in different cosolutes based on the relationship between duplex stability and the water activity of the cosolute solution. The method described herein would be valuable for investigating biological processes that occur under specific intracellular crowded conditions and for the application of DNA-based biotechnologies in crowded environments.

    DOI PubMed

  • Thrombin binding aptamer G-quadruplex stabilized by pyrene-modified nucleotides.

    Matic Kovačič, Peter Podbevšek, Hisae Tateishi-Karimata, Shuntaro Takahashi, Naoki Sugimoto, Janez Plavec

    Nucleic acids research     2020.02

    Joint Work

    Guanine-rich regions of the human genome can adopt non-canonical secondary structures. Their role in regulating gene expression has turned them into promising targets for therapeutic intervention. Ligands based on polyaromatic moieties are especially suitable for targeting G-quadruplexes utilizing their size complementarity to interact with the large exposed surface area of four guanine bases. A predictable way of (de)stabilizing specific G-quadruplex structures through efficient base stacking of polyaromatic functional groups could become a valuable tool in our therapeutic arsenal. We have investigated the effect of pyrene-modified uridine nucleotides incorporated at several positions of the thrombin binding aptamer (TBA) as a model system. Characterization using spectroscopic and biophysical methods provided important insights into modes of interaction between pyrene groups and the G-quadruplex core as well as (de)stabilization by enthalpic and entropic contributions. NMR data demonstrated that incorporation of pyrene group into G-rich oligonucleotide such as TBA may result in significant changes in 3D structure such as formation of novel dimeric topology. Site specific structural changes induced by stacking of the pyrene moiety on nearby nucleobases corelate with distinct thrombin binding affinities and increased resistance against nuclease degradation.

    DOI PubMed

  • Preferential targeting cancer-related i-motif DNAs by the plant flavonol fisetin for theranostics applications.

    Shuntaro Takahashi, Snehasish Bhattacharjee, Saptarshi Ghosh, Naoki Sugimoto, Sudipta Bhowmik

    Scientific reports   10 ( 1 ) 2504 - 2504   2020.02

    Joint Work

    The relationship of i-motif DNAs with cancer has prompted the development of specific ligands to detect and regulate their formation. Some plant flavonols show unique fluorescence and anti-cancer properties, which suggest the utility of the theranostics approach to cancer therapy related to i-motif DNA. We investigated the effect of the plant flavonol, fisetin (Fis), on the physicochemical property of i-motif DNAs. Binding of Fis to the i-motif from the promoter region of the human vascular endothelial growth factor (VEGF) gene dramatically induced the excited state intramolecular proton transfer (ESIPT) reaction that significantly enhanced the intensity of the tautomer emission band of Fis. This unique response was due to the coincidence of the structural change from i-motif to the hairpin-like structure which is stabilized via putative Watson-Crick base pairs between some guanines within the loop region of the i-motif and cytosines in the structure. As a result, the VEGF i-motif did not act as a replication block in the presence of Fis, which indicates the applicability of Fis for the regulation of gene expression of VEGF. The fluorescence and biological properties of Fis may be utilised for theranostics applications for cancers related to a specific cancer-related gene, such as VEGF.

    DOI PubMed

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Books etc 【 display / non-display

  • Quantitative Analysis of Stall of Replicating DNA Polymerase by G-Quadruplex Formation

    Shuntaro Takahashi, Naoki Sugimoto (Part: Joint Work )

    Springer  2019.08

  • 生体分子化学 基礎から応用まで

    杉本直己・編著 (Part: Joint Editor )

    講談社  2017.01 ISBN: 978-4-06-156806-8

  • 高圧下での核酸の挙動、CSJカレントレビュー17極限環境の生命化学

    高橋俊太郎,杉本直己 (Part: Joint Work )

    化学同人  2014.11

  • バイオセンシングのための水晶発振子マイクロバランス法ー原理から応用例まで

    岡畑恵雄,森俊明,古澤宏幸,高橋俊太郎 (Part: Joint Editor )

    講談社サイエンティフィク  2013.03

  • CSJカレントレビュー10ここまで進んだバイオセンシング・イメージング 1分子から細胞、脳まで

    岡畑恵雄,高橋俊太郎 (Part: Joint Work )

    化学同人  2012.11

Review Papers (Misc) 【 display / non-display

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Conference Activities & Talks 【 display / non-display

  • 核酸構造のトポロジーを基盤とする遺伝子発現制御

    高橋俊太郎

    核酸化学若手フォーラム2019  2019.10  -  2019.10 

  • Topology-based DNA quadruplex sensors for characterization of intracellular crowding environments

    S. Takahashi, J. Yamamoto, A. Kitamura, M. Kinjo, and N. Sugimoto

    第46回国際核酸化学シンポジウム  (宮地楽器ホール)  2019.10  -  2019.10 

  • Prediction method for DNA duplex stability in molecular crowding conditions

    S. Ghosh, S. Takahashi, T. Ohyama, T. Endoh, H. Kateishi-Karimata, and N. Sugimoto

    第46回国際核酸化学シンポジウム  (宮地楽器ホール)  2019.10  -  2019.10 

  • Development of new prediction parameters for RNA/DNA hybrid duplex stability under a physiological buffer condition

    D. Banerjee, H. Tateishi-Karimata, T. Ohyama, T. Endoh, S. Takahashi, and N. Sugimoto

    第46回国際核酸化学シンポジウム  (宮地楽器ホール)  2019.10  -  2019.10 

  • Analysis of ligand binding on G-quadruplex using high pressure

    S. Takahashi

    The 7th International Meeting on Quadruplex Nucleic Acids, Chinese Academy of Sciences  (Changchun, China)  2019.09  -  2019.09 

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

  • Grant-in-Aid for Scientific Research(C)

    Project Year: 2017.04  -  2021.03 

  • Grant-in-Aid for Scientific Research(C)

    Project Year: 2014.04  -  2017.03 

  • Grant-in-Aid for Young Scientists(B)

    Project Year: 2012.04  -  2014.03 

  • Grant-in-Aid for Young Scientists(B)

    Project Year: 2010.04  -  2012.03