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Affiliation |
Organization for Promotion of Research and Industry-Academic Regional Collaboration Institute for Tenure Track Promotion |
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Title |
Lecturer |
IWANO satoshi
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Research Areas 【 display / non-display 】
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Nanotechnology/Materials / Chemical biology
Papers 【 display / non-display 】
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A non-invasive system to monitor in vivo neural graft activity after spinal cord injury Reviewed International journal
Kentaro Ago, Narihito Nagoshi, Kent Imaizumi, Takahiro Kitagawa, Momotaro Kawai, Keita Kajikawa, Reo Shibata, Yasuhiro Kamata, Kota Kojima, Munehisa Shinozaki, Takahiro Kondo, Satoshi Iwano, Atsushi Miyawaki, Masanari Ohtsuka, Haruhiko Bito, Kenta Kobayashi, Shinsuke Shibata, Tomoko Shindo, Jun Kohyama, Morio Matsumoto, Masaya Nakamura, Hideyuki Okano
Communications Biology 5 ( 1 ) 803 - 803 2022.8
Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC
Abstract
Expectations for neural stem/progenitor cell (NS/PC) transplantation as a treatment for spinal cord injury (SCI) are increasing. However, whether and how grafted cells are incorporated into the host neural circuit and contribute to motor function recovery remain unknown. The aim of this project was to establish a novel non-invasive in vivo imaging system to visualize the activity of neural grafts by which we can simultaneously demonstrate the circuit-level integration between the graft and host and the contribution of graft neuronal activity to host behaviour. We introduced Akaluc, a newly engineered luciferase, under the control of enhanced synaptic activity-responsive element (E-SARE), a potent neuronal activity-dependent synthetic promoter, into NS/PCs and engrafted the cells into SCI model mice. Through the use of this system, we found that the activity of grafted cells was integrated with host behaviour and driven by host neural circuit inputs. This non-invasive system is expected to help elucidate the therapeutic mechanism of cell transplantation treatment for SCI.DOI： 10.1038/s42003-022-03736-8
Other Link： https://www.nature.com/articles/s42003-022-03736-8
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Functional visualization of NK Cell-mediated killing of metastatic single tumor cells International journal
Ichise Hiroshi, Tsukamoto Shoko, Hirashima Tsuyoshi, Konishi Yoshinobu, Oki Choji, Tsukiji Shinya, Iwano Satoshi, Miyawaki Atsushi, Sumiyama Kenta, Terai Kenta, Matsuda Michiyuki
eLife 11 2022.2
Language：English Publishing type：Research paper (scientific journal)
Natural killer (NK) cells lyse invading tumor cells to limit metastatic growth in the lung, but how some cancers evade this host protective mechanism to establish a growing lesion is unknown. Here we have combined ultra-sensitive bioluminescence imaging with intravital two-photon microscopy involving genetically-encoded biosensors to examine this question. NK cells eliminated disseminated tumor cells from the lung within 24 hrs of arrival, but not thereafter. Intravital dynamic imaging revealed that 50% of NK-tumor cell encounters lead to tumor cell death in the first 4 hrs after tumor cell arrival, but after 24 hrs of arrival, nearly 100% of the interactions result in the survival of the tumor cell. During this 24 hrs period, the probability of ERK activation in NK cells upon encountering the tumor cells was decreased from 68% to 8%, which correlated with the loss of the activating ligand CD155/PVR/Necl5 from the tumor cell surface. Thus, by quantitatively visualizing the NK-tumor cell interaction at the early stage of metastasis, we have revealed the crucial parameters of NK cell immune surveillance in the lung.
DOI： 10.7554/eLife.76269
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Kamiya Genta, Kitada Nobuo, Saito-Moriya Ryohei, Obata Rika, Iwano Satoshi, Miyawaki Atsushi, Hirano Takashi, Maki Shojiro A.
Chemistry Letters 50 ( 8 ) 1523 - 1525 2021.5
Language：English Publishing type：Research paper (scientific journal) Publisher：The Chemical Society of Japan
Firefly bioluminescence, which produces high-efficiency light, is widely used in life science applications. For <i>in vivo</i> bioluminescence imaging, the near-infrared range (650–900 nm) is suitable because of its high permeability in deep biological tissues. In this study, we synthesized new luciferin analogues that emit light at 765 nm using <i>Photinus pyralis</i> luciferase.
DOI： 10.1246/cl.210261
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DHODH inhibition synergizes with DNA-demethylating agents in the treatment of myelodysplastic syndromes. Reviewed International journal
Kensuke Kayamori, Yurie Nagai, Cheng Zhong, Satoshi Kaito, Daisuke Shinoda, Shuhei Koide, Wakako Kuribayashi, Motohiko Oshima, Yaeko Nakajima-Takagi, Masayuki Yamashita, Naoya Mimura, Hans Jiro Becker, Kiyoko Izawa, Satoshi Yamazaki, Satoshi Iwano, Atsushi Miyawaki, Ryoji Ito, Kaoru Tohyama, William Lennox, Josephine Sheedy, Marla Weetall, Emiko Sakaida, Koutaro Yokote, Atsushi Iwama
Blood advances 5 ( 2 ) 438 - 450 2021.1
Language：English Publishing type：Research paper (scientific journal) Publisher：Blood Advances
Dihydroorotate dehydrogenase (DHODH) catalyzes a rate-limiting step in de novo pyrimidine nucleotide synthesis. DHODH inhibition has recently been recognized as a potential new approach for treating acute myeloid leukemia (AML) by inducing differentiation. We investigated the efficacy of PTC299, a novel DHODH inhibitor, for myelodysplastic syndrome (MDS). PTC299 inhibited the proliferation of MDS cell lines, and this was rescued by exogenous uridine, which bypasses de novo pyrimidine synthesis. In contrast to AML cells, PTC299 was inefficient at inhibiting growth and inducing the differentiation of MDS cells, but synergized with hypomethylating agents, such as decitabine, to inhibit the growth of MDS cells. This synergistic effect was confirmed in primary MDS samples. As a single agent, PTC299 prolonged the survival of mice in xenograft models using MDS cell lines, and was more potent in combination with decitabine. Mechanistically, a treatment with PTC299 induced intra-S-phase arrest followed by apoptotic cell death. Of interest, PTC299 enhanced the incorporation of decitabine, an analog of cytidine, into DNA by inhibiting pyrimidine production, thereby enhancing the cytotoxic effects of decitabine. RNA-seq data revealed the marked downregulation of MYC target gene sets with PTC299 exposure. Transfection of MDS cell lines with MYC largely attenuated the growth inhibitory effects of PTC299, suggesting MYC as one of the major targets of PTC299. Our results indicate that the DHODH inhibitor PTC299 suppresses the growth of MDS cells and acts in a synergistic manner with decitabine. This combination therapy may be a new therapeutic option for the treatment of MDS.
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Efficacy of the novel tubulin polymerization inhibitor PTC‐028 for myelodysplastic syndrome Reviewed
Cheng Zhong, Kensuke Kayamori, Shuhei Koide, Daisuke Shinoda, Motohiko Oshima, Yaeko Nakajima‐Takagi, Yurie Nagai, Naoya Mimura, Emiko Sakaida, Satoshi Yamazaki, Satoshi Iwano, Atsushi Miyawaki, Ryoji Ito, Kaoru Tohyama, Kiyoshi Yamaguchi, Yoichi Furukawa, William Lennox, Josephine Sheedy, Marla Weetall, Atsushi Iwama
Cancer Science 111 ( 12 ) 4336 - 4347 2020.11
Language：English Publishing type：Research paper (scientific journal) Publisher：Wiley
Monomer tubulin polymerize into microtubules, which are highly dynamic and play a critical role in mitosis. Therefore, microtubule dynamics are an important target for anticancer drugs. The inhibition of tubulin polymerization or depolymerization was previously targeted and exhibited efficacy against solid tumors. The novel small molecule PTC596 directly binds tubulin, inhibits microtubule polymerization, downregulates MCL-1, and induces p53-independent apoptosis in acute myeloid leukemia cells. We herein investigated the efficacy of PTC-028, a structural analog of PTC596, for myelodysplastic syndrome (MDS). PTC-028 suppressed growth and induced apoptosis in MDS cell lines. The efficacy of PTC028 in primary MDS samples was confirmed using cell proliferation assays. PTC-028 synergized with hypomethylating agents, such as decitabine and azacitidine, to inhibit growth and induce apoptosis in MDS cells. Mechanistically, a treatment with PTC-028 induced G2/M arrest followed by apoptotic cell death. We also assessed the efficacy of PTC-028 in a xenograft mouse model of MDS using the MDS cell line, MDS-L, and the AkaBLI bioluminescence imaging system, which is composed of AkaLumine-HCl and Akaluc. PTC-028 prolonged the survival of mice in xenograft models. The present results suggest a chemotherapeutic strategy for MDS through the disruption of microtubule dynamics in combination with DNA hypomethylating agents.
DOI： 10.1111/cas.14684
Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/cas.14684
Presentations 【 display / non-display 】
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生物発光を利用した脳機能の非侵襲イメージング Invited
岩野 智
第127回日本解剖学会総会 2022.3.28
Event date： 2022.3.27 - 2022.3.29
Language：Japanese Presentation type：Symposium, workshop panel (nominated)
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Development of Bioluminescence probe for non-invasive in vivo imaging in animal Invited
Satoshi Iwano
The 44th Annual Meeting of the Molecular Biology Society of Japan 2021.12.1
Event date： 2021.12.1 - 2021.12.3
Presentation type：Symposium, workshop panel (nominated)
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Bioluminescence imaging of deep tissue in freely moving animals Invited
Satoshi Iwano
The 80th Annual Meeting of the Japanese Cancer Association 2021.10.2
Event date： 2021.9.30 - 2021.10.2
Presentation type：Symposium, workshop panel (nominated)
Awards 【 display / non-display 】
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バイオインダストリー奨励賞
2020.10 Japan Bioindustry Association
Award type：International academic award (Japan or overseas)
Grant-in-Aid for Scientific Research 【 display / non-display 】
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心身相関を担う皮質辺縁系神経回路メカニズムの解明
Grant number：23H00398 2023.04 - 2027.03
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（A）
Authorship：Coinvestigator(s)
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自由行動動物の深部臓器における細胞応答の光イメージング
Grant number：23K17389 2023.04 - 2026.03
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）
Authorship：Coinvestigator(s)
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生命科学研究を拓く生物発光技術の開発
Grant number：20H03178 2022.04 - 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(B)
Authorship：Principal investigator