部門付

研究課題

生きた細胞やオルガノイドの解析と操作を目的として、ダメージを与えないナノ材料を用いた技術を開発しています。本研究では、原子間力顕微鏡AFMを用いて、ピコニュートンからマイクロニュートンの微小な力を測定し、抗体と標的膜タンパク質の相互作用や、生きた細胞の弾性、接着力を明らかにするセルメカニクスを基盤技術としています。具体的には、直径200 nmのナノニードルを用いたゲノム編集、新規がんモデルの構築、がん治療抗体の開発などに取り組んでいます。

• https://unit.aist.go.jp/cmb5/chikashi-nakamura/index.html

医薬品などの安全性や機能性を評価するバイオ試験法の高度化は喫緊の課題です。ヒトや動物の生理機能を含む生体反応のしくみを指す「バイオシステム」の評価は、これまで主に動物実験に依存してきましたが、近年はその代替技術への転換が世界的に進み、「バイオシステム代替学」という新たな学術領域の確立が求められています。 私たちは、新規アプローチ手法（NAMs）、オミクス解析、in silicoシミュレーションなどを活用し、ヒトに近い予測性と再現性を備えた評価プラットフォームの構築に取り組んでいます。

本研究では、生体模倣システム（MPS: Microphysiological Systems）と多様な細胞や組織を組み合わせることで、ヒトの生体環境に近い高度な評価系の構築を目指します。従来の評価系では捉えきれなかった自律神経系・免疫系・血管系を介した生理応答や薬剤作用のメカニズム解析を可能にします。MPSを含むNAMsと、オミクスデータ解析・in silicoシミュレーションなどのデジタル技術を融合し、化合物の作用を予測可能な安全性評価システムの開発に取り組んでいます。

また、ヒトiPS細胞に加え、ラット・マウス・ウサギなどの実験動物由来のiPS細胞や幹細胞も活用し、動物実験の代替となる評価系や種間比較が可能な新たなモデルの構築を進めています。 加えて、本研究では、 このシステムは、創薬や食品分野にとどまらず、住環境ソリューションへの応用も視野に入れており、建材・内装材・家電製品に含まれる化学物質の安全性評価を、in vitro × in silico 手法で実現することを目指しています。

これにより、動物実験に依存せず、かつヒトへの影響をより的確に予測できる革新的な評価技術として、規制対応の迅速化や製品開発における信頼性の向上に資する研究開発を推進します。こうしたバイオ技術・バイオ製造プロセス・バイオ評価手法は、バイオものづくりを含むバイオ産業全体の高度化・持続可能性の向上にも大きく貢献することが期待されます。

業績リスト

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• Kato, A; Iwasaki, R; Takeshima, K; Maruzuru, Y; Koyanagi, N; Natsume, T; Kusano, H; Adachi, S; Kawano, S; Kawaguchi, Y.
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• Song, X; Nihashi, Y; Imai, Y; Mori, N; Kagaya, N; Suenaga, H; Shin-Ya, K; Yamamoto, M; Setoyama, D; Kunisaki Y; Kida, YS .
  Collagen Lattice Model, Populated with Heterogeneous Cancer-Associated Fibroblasts, Facilitates Advanced Reconstruction of Pancreatic Cancer Microenvironment.
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• Kudo, K; Nishimura, T; Izumikawa, M; Kozone, I; Hashimoto, J; Fujie, M; Suenaga, H; Ikeda, H; Satoh, N; Shin-Ya, K.
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• Dong, W; Kameyama, A.
  Succinylation-Alcian Blue Staining of Mucins on Polyvinylidene Difluoride Membrane.
  METHODS MOL BIOL. 2024;2763:111-117. doi: 10.1007/978-1-0716-3670-1_9
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• Sugiura, T; Kameyama, A.
  Preparation of Soluble Mucin Solutions from the Salivary Glands.
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• Hashimoto, T; Suenaga, H; Amagai, K; Hashimoto, J; Kozone, I; Takahashi, S; Shin-Ya, K.
  In Vitro Module Editing Of NRPS Enables Production Of Highly Potent Gq-Signaling Inhibitor FR900359 Derived From Unculturable Plant Symbiont.
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• Song, X; Nihashi, Y; amamoto, M; Setoyama, D; Kunisaki, Y; Kida, YS.
  Exploring the Role of Desmoplastic Physical Stroma in Pancreatic Cancer Progression Using a Three-Dimensional Collagen Matrix Model.
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• Akagi, Y; Takayama, Y; Nihashi, Y; Yamashita, A; Yoshida, R; Miyamoto, Y; Kida, YS.
  Functional engineering of human iPSC-derived parasympathetic neurons enhances responsiveness to gastrointestinal hormones.
  FEBS OPEN BIO. 2023 Nov 27. doi: 10.1002/2211-5463.13741
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  Shell protein composition specified by the lncRNA NEAT1 domains dictates the formation of paraspeckles as distinct membraneless organelles.
  NAT CELL BIOL. 2023 Nov 6. doi: 10.1038/s41556-023-01254-1
• Ishii, N; Noguchi, K; Ikemoto, MJ; Yohda, M; Odahara, T.
  Optimizing Exosome Preparation Based on Size and Morphology: Insights From Electron Microscopy.
  MICROSC MICROANAL. 2023 Oct 13:ozad103. doi: 10.1093/micmic/ozad103
• Ishii, N; Odahara, T.
  Investigation of the Efficacy of Lanthanoid Heavy Metal Acetates as Electron Staining Reagents for Biomembrane Vesicles.
  MICROSC MICROANAL. 2023 Oct 13:ozad107. doi: 10.1093/micmic/ozad107
• Ishioka, M; Nihashi, Y; Sunagawa, Y; Umezawa, K; Shimosato, T; Kagami, H; Morimoto, T; Takaya, T.
  Myogenetic Oligodeoxynucleotide Induces Myocardial Differentiation of Murine Pluripotent Stem Cells.
  INT J MOL SCI. 2023 Sep 21;24(18):14380. doi: 10.3390/ijms241814380
• Miyazawa, K; Penedo, M; Furusho, H; Ichikawa, T; Alam, MS; Miyata, K; Nakamura, C; Fukuma, T.
  Nanoendoscopy-AFM for Visualizing Intracellular Nanostructures of Living Cells.
  MICROSC MICROANAL. 2023 Jul 22;29(Supplement_1):782. doi: 10.1093/micmic/ozad067.387
• Takubo, K; Htun, PW; Ueda, T; Sera, Y; Iwasaki, M; Koizumi, M; Shiroshita, K; Kobayashi, H; Haraguchi, M; Watanuki, S; Honda, ZI; Yamasaki, N; Nakamura-Ishizu, A; Arai, F; Motoyama, N; Hatta, T; Natsume, T; Suda, T; Honda, H.
  MBTD1 preserves adult hematopoietic stem cell pool size and function.
  PROC NATL ACAD SCI U S A. 2023 Aug 8;120(32):e2206860120. doi: 10.1073/pnas.2206860120
• Ichikawa, T; Alam, MS; Penedo, M; Matsumoto, K; Fujita, S; Miyazawa, K; Furusho, H; Miyata, K; Nakamura, C; Fukuma, T.
  Protocol for live imaging of intracellular nanoscale structures using atomic force microscopy with nanoneedle probes.
  STAR PROTOC. 2023 Jul 22;4(3):102468. doi: 10.1016/j.xpro.2023.102468
• Miyashita, K; Yagi, T; Kagaya, N; Takechi, A; Nakata, C; Kanda, R; Nuriya, H; Tanegashima, K; Hoyano, S; Seki, F; Yoshida, C; Hachiro, Y; Higashi, T; Kitada, N; Toya, T; Kobayashi, T; Najima, Y; Goyama, S; Maki, SA; Kitamura, T; Doki, N; Shin-Ya, K; Hara, T.
  Identification of compounds that preferentially suppress the growth of T-cell acute lymphoblastic leukemia-derived cells.
  CANCER SCI. 2023 Jul 31. doi: 10.1111/cas.15918
• Nihashi, Y, Song, X; Yamamoto, M; Setoyama, D; Kida, YS.
  Decoding Metabolic Symbiosis between Pancreatic Cancer Cells and Cancer-Associated Fibroblasts Using Cultured Tumor Microenvironment.
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• Taniguchi, M; Okumura, R; Matsuzaki, T; Nakatani, A; Sakaki, K; Okamoto, S; Ishibashi, A; Tani, H; Horikiri, M; Kobayashi, N; Yoshikawa, HY; Motooka, D; Okuzaki, D; Nakamura, S; Kida, T; Kameyama, A, Takeda, K.
  Sialylation shapes mucus architecture inhibiting bacterial invasion in the colon.
  MUCOSAL IMMUNOL. 2023 Jun 27:S1933-0219(23)00049-1. doi: 10.1016/j.mucimm.2023.06.004
• Roberts, MD; McCarthy, JJ; Hornberger, TA; Phillips, SM; Mackey, AL; Nader, GA; Boppart, MD; Kavazis, AN; Reidy, PT; Ogasawara, R, Libardi, CA; Ugrinowitsch, C; Booth, FW; Esser, KA.
  Mechanisms of mechanical overload-induced skeletal muscle hypertrophy: current understanding and future directions.
  PHYSIOL REV. 2023 Jun 29. doi: 10.1152/physrev.00039.2022
• Zhuang, HT; Fujikura, Y, Ohkura, N; Higo-Yamamoto, S; Mishima, T; Oishi, K.
  A ketogenic diet containing medium-chain triglycerides reduces REM sleep duration without significant influence on mouse circadian phenotypes.
  FOOD RESEARCH INTERNATIONAL. 2023 Jul;169:112852. doi: 10.1016/j.foodres.2023.112852
• Takayama, Y, Akagi, Y, Kida, YS.
  Deciphering the Molecular Mechanisms of Autonomic Nervous System Neuron Induction through Integrative Bioinformatics Analysis.
  INT J MOL SCI. 2023 May 21;24(10):9053. doi: 10.3390/ijms24109053
• Arima, K; Akiyama, S; Shin-Ya, K; Matsuda, K; Wakimoto, T.
  Carrier Protein Mediated Formation of the Dihydropyridazinone Ring in Actinopyridazinone Biosynthesis.
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• Kumagai, Y; Saito, Y; Kida, YS.
  A multiomics atlas of brown adipose tissue development over time.
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• Sugiura, T; Hashimoto, K; Kikuta, K; Anazawa, U; Nomura, T; Kameyama, A.
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• Ikemoto, MJ; Aihara, Y; Ishii, N; Shigemori, H.
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• Murata, Y; Jitsukawa, T; Iida, M; Furuta, T; Haramoto, Y; Shigeri, Y; Fujisaki, S.
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  Acyltransferase Domain Exchange between Two Independent Type I Polyketide Synthases in the Same Producer Strain of Macrolide Antibiotics.
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  Myogenetic Oligodeoxynucleotides as Anti-Nucleolin Aptamers Inhibit the Growth of Embryonal Rhabdomyosarcoma Cells.
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  Therapeutic Potential of Adipose Stem Cell-Derived Conditioned Medium on Scar Contraction Model.
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• Tirta, YK; Adachi, S; Perez, CAG; Adhitama, N; Nong, QD; Natsume, T; Kato, Y; Watanabe, H.
  CELF1 represses Doublesex1 expression via its 5 UTR in the crustacean Daphnia magna.
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  RNAapt3D: RNA aptamer 3D-structural modeling database.
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• Kawai, S; Hagihara, R; Shin-Ya, K; Katsuyama, Y; Ohnishi, Y.
  Bacterial Avenalumic Acid Biosynthesis Includes Substitution of an Aromatic Amino Group for Hydride by Nitrous Acid Dependent Diazotization.
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