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研究・産学地域連携推進機構 テニュアトラック推進室 |
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講師 |
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A non-invasive system to monitor in vivo neural graft activity after spinal cord injury 査読あり 国際誌
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年8月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：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. -
Functional visualization of NK cell-mediated killing of metastatic single tumor cells. 国際誌
Hiroshi Ichise, Shoko Tsukamoto, Tsuyoshi Hirashima, Yoshinobu Konishi, Choji Oki, Shinya Tsukiji, Satoshi Iwano, Atsushi Miyawaki, Kenta Sumiyama, Kenta Terai, Michiyuki Matsuda
eLife 11 2022年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：eLife Sciences Publications, Ltd
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 hr 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 hr after tumor cell arrival, but after 24 hr of arrival, nearly 100% of the interactions result in the survival of the tumor cell. During this 24-hr 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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Genta Kamiya, Nobuo Kitada, Ryohei Saito-Moriya, Rika Obata, Satoshi Iwano, Atsushi Miyawaki, Takashi Hirano, Shojiro Maki
Chemistry Letters 50 ( 8 ) 1523 - 1525 2021年5月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：The Chemical Society of Japan
Firefly bioluminescence, which produces high-efficiency light, is widely used in life science applications. For in vivo bioluminescence imaging, the near-infrared range (650900 nm) is suitable because of its high permeability in deep biological tissues. In this study, we synthesized new luciferin analogues that emit light at 765nm using Photinus pyralis luciferase.
DOI： 10.1246/cl.210261
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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年1月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：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 査読あり
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年11月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：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
その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/cas.14684
講演・口頭発表等 【 表示 ／ 非表示 】
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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 招待あり
岩野 智
第127回日本解剖学会総会 2022年3月28日
開催年月日： 2022年3月27日 - 2022年3月29日
記述言語：日本語 会議種別：シンポジウム・ワークショップ パネル（指名）
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生物発光を利用したバイオイメージング技術の開発 招待あり
岩野 智
第44回日本分子生物学会年会 2021年12月1日
開催年月日： 2021年12月1日 - 2021年12月3日
会議種別：シンポジウム・ワークショップ パネル（指名）
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動物にやさしいin vivo発光イメージング 招待あり
岩野 智
第80回日本癌学会学術総会 2021年10月2日
開催年月日： 2021年9月30日 - 2021年10月2日
会議種別：シンポジウム・ワークショップ パネル（指名）
科研費（文科省・学振・厚労省）獲得実績 【 表示 ／ 非表示 】
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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
研究課題/領域番号：23H00398 2023年04月 - 2027年03月
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）
担当区分：研究分担者
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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
研究課題/領域番号：23K17389 2023年04月 - 2026年03月
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）
担当区分：研究分担者
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生命科学研究を拓く生物発光技術の開発
研究課題/領域番号：20H03178 2022年04月 - 2024年03月
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)
担当区分：研究代表者
その他競争的資金獲得実績 【 表示 ／ 非表示 】
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生物発光反応に基づく機能プローブ技術の開発と動物個体深部における分子活性の高感度イメージングの実現
2023年04月 - 2025年03月
中島記念国際交流財団 令和５年度若手研究者研究助成金
担当区分：研究代表者
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コロナウイルスの感染動態を読み解く生物発光イメージング技術の開発
2023年04月 - 2024年03月
新日本先進医療研究財団 令和4年度助成金
担当区分：研究代表者
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動物個体深部での特定分子の活性を非侵襲的に可視化する生物発光技術の開発
2022年11月
伊藤化学振興会 研究助成金
担当区分：研究代表者
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指向性進化による生物発光酵素の機能拡張とその利用
2022年05月 - 2023年09月
日本応用酵素協会 酵素研究助成
担当区分：研究代表者
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個体深部での特定分子の活性を非侵襲的検出する生物発光技術の開発
2022年03月 - 2024年03月
島津科学技術振興財団 研究開発助成金
担当区分：研究代表者
共同研究実施実績 【 表示 ／ 非表示 】
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生物発光の材料化技術に関する研究
2023年04月 - 2024年03月
株式会社キャンパスクリエイト、国立大学法人電気通信大学 国内共同研究
担当区分：研究代表者 共同研究区分：国内共同研究