NAKANISHI, Jun

写真a

Affiliation

Faculty of Science and Engineering, Graduate School of Advanced Science and Engineering

Job title

Professor(without tenure)
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Research Institute 【 display / non-display 】

  • 2020
    -
    2022

    理工学術院総合研究所   兼任研究員

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Education 【 display / non-display 】

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    2001

    The University of Tokyo  

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    2001

    The University of Tokyo   Graduate School, Division of Science   Department of Chemistry  

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    1996

    The University of Tokyo   Faculty of Science   Department of Chemistry  

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Degree 【 display / non-display 】

  • Doctor of Science

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Research Experience 【 display / non-display 】

  • 2016.04
    -
    Now

    National Institute for Materials Science   Group Leader

  • 2007.10
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    2016.03

    National Institute for Materials Science   Independent Scientist

  • 2005.10
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    2009.03

    科学技術振興機構 さきがけ研究者

  • 2006.10
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    2007.09

    物質・材料研究機構 主任研究員

  • 2005.04
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    2005.09

    Waseda University   Consolidated Research Institute for Advanced Science and Medical Care

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Professional Memberships 【 display / non-display 】

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    日本化学会

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    日本生化学会

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    日本バイオマテリアル学会

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    日本高分子学会

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    日本分析化学会

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Research Areas 【 display / non-display 】

  • Nanobioscience

  • Chemical biology

  • Analytical chemistry

  • Biomaterials

  • Biomedical engineering

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Research Interests 【 display / non-display 】

  • Mechanobiology

  • Biomaterials

  • 細胞外マトリクス

  • 蛍光イメージング

  • ケージド化合物

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Papers 【 display / non-display 】

  • Viscoelastically tunable substrates elucidate the interface-relaxation-dependent adhesion and assembly behaviors of epithelial cells.

    Alice Chinghsuan Chang, Koichro Uto, Kenta Homma, Jun Nakanishi

    Biomaterials   274   120861 - 120861  2021.07  [International journal]

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    Recent progress in mechanobiology sheds light on the regulation of cellular phenotypes by dissipative property of matrices, i.e., viscosity, fluidity, and stress relaxation, in addition to extensively studied elasticity. However, most researches have focused on bulk mechanics, despite cells in 2D culture can only interact with matrix interface directly. Here, we studied the impact of interfacial viscosity as well as elasticity of substrates on the early stage of adhesion behaviors of epithelial cells through new material design and mechanical characterization. The materials are copolymers of ε-caprolactone and d,l-lactide photocrosslinked by benzophenone. The substrate viscoelasticity changes depending on the polymer molecular weight and irradiation time. The interfacial elasticity and relaxation were determined by atomic force microscopy with modes of nanoindentation and tip-dwelling, respectively. MDCK cells changed morphologically, ranging from loose beaded assembly to more compact spheroids and eventual spread monolayer clusters, in response to the interfacial viscoelasticity change. Such morphological changes were mainly determined by substrate interfacial relaxation, rather than interfacial elasticity. Single-cell tracking identified biphasic motility with the minimum speed at intermediate relaxation time (~350 ms), where cells showed transitional morphologies between epithelial and mesenchymal traits. In that relaxation level, partially deformed cells moved around to coalesce with surrounding cells, eventually assembling into compact cellular aggregates. These results highlight, unlike the conventional hanging-drop technique, an appropriate level of interfacial relaxation is critical for efficient cell aggregate maturation on adhesive viscoelastic matrices. This work not only elucidates that the interfacial relaxation as the essential mechanical parameter for epithelial cell adhesion and migration, but also gives useful tips for creating physiologically relevant drug screening platform.

    DOI PubMed

  • Epidermal Growth Factor-gold Nanoparticle Conjugates-induced Cellular Responses: Effect of Interfacial Parameters between Cell and Nanoparticle

    Shota Yamamoto, Jun Nakanishi

    ANALYTICAL SCIENCES   37 ( 5 ) 741 - 745  2021.05

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    The original activity of epidermal growth factor (EGF) is to promote cell growth or block their apoptosis. However, its activity changes to proapoptotic, completely opposite to the original one, upon conjugation to nanoparticles. We have recently identified that this unique activity conversion was mediated by the confinement of EGF receptor (EGFR) within membrane rafts and signal condensation therein. In this study, we investigated the effect of interfacial parameters between the EGF molecule immobilized at the nanoparticle surface and the cell-surface membrane receptors and analyzed how their interactions were transduced to downstream signaling leading to apoptotic responses. We also studied the cell-type selective apoptotic responses and compared them with EGFR expression level to demonstrate the potential of the nanoparticle conjugate as a new type of anti-cancer drug activating EGFR rather than conventional blocking approaches.

    DOI

  • Nanaomycin K inhibited epithelial mesenchymal transition and tumor growth in bladder cancer cells in vitro and in vivo.

    Koichi Kitagawa, Katsumi Shigemura, Aya Ishii, Takuji Nakashima, Hirotaka Matsuo, Yoko Takahashi, Satoshi Omura, Jun Nakanishi, Masato Fujisawa

    Scientific reports   11 ( 1 ) 9217 - 9217  2021.04  [International journal]

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    Nanaomycin K, derived from Streptomyces rosa subsp. notoensis OS-3966T, has been discovered to have inhibitory bioactivity on epithelial-mesenchymal transition (EMT), an important mechanism of cancer cell invasion and migration. In this study, we examined the anti-EMT and anti-tumor effect of nanaomycin K in bladder cancer, where EMT has important roles in progression. We treated two bladder cancer lines, non-muscle-invasive KK47 and muscle-invasive T24, with nanaomycin K to determine the effects on cell proliferation, apoptosis and expression of EMT markers in vitro. Wound-healing assays were performed to assess cell invasion and migration. We conducted an in vivo xenograft study in which mice were inoculated with bladder cancer cells and treated with intratumoral administration of nanaomycin K to investigate its anti-tumor and EMT inhibition effects. As the results, nanaomycin K (50 µg/mL) significantly inhibited cell proliferation in KK47 (p < 0.01) and T24 (p < 0.01) in the presence of TGF-β, which is an EMT-inducer. Nanaomycin K (50 µg/mL) also significantly inhibited cell migration in KK47 (p < 0.01) and T24 (p < 0.01), and induced apoptosis in both cell lines in the presence of TGF-β (p < 0.01). Nanaomycin K increased the expression of E-cadherin and inhibited the expression of N-cadherin and vimentin in both cell lines. Nanaomycin K also decreased expression of Snail, Slug, phospho-p38 and phospho-SAPK/JNK especially in T24. Intratumoral administration of nanaomycin K significantly inhibited tumor growth in both KK47 and T24 cells at high dose (1.0 mg/body) (p = 0.009 and p = 0.003, respectively) with no obvious adverse events. In addition, nanaomycin K reversed EMT and significantly inhibited the expression of Ki-67 especially in T24. In conclusion, we demonstrated that nanaomycin K had significant anti-EMT and anti-tumor effects in bladder cancer cells, suggesting that nanaomycin K may be a therapeutic candidate for bladder cancer treatment.

    DOI PubMed

  • Design of azobenzene-bearing hydrogel with photoswitchable mechanics driven by photo-induced phase transition for in vitro disease modeling.

    Kenta Homma, Alice C Chang, Shota Yamamoto, Ryota Tamate, Takeshi Ueki, Jun Nakanishi

    Acta biomaterialia    2021.03  [International journal]

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    Mechanics of the extracellular matrix (ECM) exhibit changes during many biological events. During disease progression, such as cancer, matrix stiffening or softening occurs due to crosslinking of the collagen matrix or matrix degradation through cell-secreted enzymes. Engineered hydrogels have emerged as a prime in vitro model to mimic such dynamic mechanics during disease progression. Although there have been a variety of engineered hydrogels, few can offer both stiffening and softening properties under the same working principle. In addition, to model individual disease progression, it is desirable to control the kinetics of mechanical changes. To this end, we describe a photoresponsive hydrogel that undergoes stiffness changes by the photo-induced phase transition. The hydrogel was composed of a copolymer of azobenzene acrylate monomer (AzoAA) and N,N-dimethyl acrylamide (DMA). By tuning the amount of azobenzene, the phase transition behavior of this polymer occurs solely by light irradiation, because of the photoisomerization of azobenzene. This phase behavior was confirmed at 37 °C by turbidity measurements. In addition, the crosslinked poly(AzoAA-r-DMA) gel undergoes reversible swelling-deswelling upon photoisomerization by ultraviolet or visible light. Furthermore, the poly(AzoAA-r-DMA) sheet gels exhibited modulus changes at different isomerization states of azobenzene. When MCF-7 cells were cultured on the gels, stiffening at different timepoints induced varied responses in the gene expression levels of E-cadherin. Not only did this suggest an adaptive behavior of the cells against changes in mechanics during disease progression, this also demonstrated our material's potential towards in vitro disease modeling. STATEMENT OF SIGNIFICANCE: During disease progression such as cancer, cellular microenvironment called extracellular matrix (ECM) undergoes stiffness changes. Hydrogels, which are swollen network of crosslinked polymers, have been used to model such dynamic mechanical environment of the ECM. However, few could offer both stiffening and softening properties under the same working principle. Herein, we fabricated a novel photoresponsive hydrogel with switchable mechanics, activated by photo-induced structural change of the polymer chains within the hydrogel. When breast cancer cells were cultured on our dynamic hydrogels, gene expression and morphological observation suggested that cells react to changes in stiffness by a transient response, as opposed to a sustained one. The photoresponsive hydrogel offers possibility for use as a patient-specific model of diseases.

    DOI PubMed

  • Large-Area Aligned Fullerene Nanocrystal Scaffolds as Culture Substrates for Enhancing Mesenchymal Stem Cell Self-Renewal and Multipotency

    Jingwen Song, Xiaofang Jia, Kosuke Minami, Jonathan P. Hill, Jun Nakanishi, Lok Kumar Shrestha, Katsuhiko Ariga

    ACS Applied Nano Materials   3 ( 7 ) 6497 - 6506  2020.07

    DOI

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Misc 【 display / non-display 】

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Industrial Property Rights 【 display / non-display 】

  • 蛍光顕微鏡下における細胞接着の光スイッチング法

    Patent

    　View Summary

    特願２００４－１８８４６１

  • 蛍光顕微鏡下における細胞接着の光スイッチング法

    Patent

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    特願２００４－１８８４６１

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Works 【 display / non-display 】

  • 細胞のパターニング技術の開発

    2003
    -
    2005

  • Development of Cell Patterning Technology

    2002
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    2005

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Awards 【 display / non-display 】

  • Young Scientists' Prize

    2011.04   Minister of MEXT  

    Winner： NAKANISHI Jun

  • Japan Society of Analytical Chemistry Award for Younger Researchers

    2009.09   Japan Society for Analytical Chemistry  

    Winner： NAKANISHI Jun

  • 日本分析化学会 イノベーション賞

    2006  

  • 2005高木賞（第14回インテリジェント材料・システムシンポジウム）

    2005  

  • 2005 Takagi Awards (14th Intelligent Materials and System Symposium)

    2005  

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Research Projects 【 display / non-display 】

  • 時空間を制限した細胞内シグナルの発生とその計測

    Project Year :

    2005
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    2009
     

  • Generation and Measurement of Spatially and Temporally Controlled Intracellular Signaling

    Project Year :

    2005
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    2009
     

  • ケージド化合物の創成

    Project Year :

    2006
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  • Development of Cell-based Sensors

    Project Year :

    2002
    -
    2005
     

  • Cell Patterning

    Project Year :

    2002
    -
    2005
     

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Syllabus 【 display / non-display 】

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