Okinaka M, Kawatani M, Fujioka H, Spratt S, Ito H, Misawa Y, Otake R, Ishikawa A, Kojima R, Urano Y, Ozeki Y, Kamiya M*. Functional Raman probes for detecting enzyme activities based on aggregation control. Anal. Chem. 97, 19057–19065 (2025).
【研究概要】生体内で働く様々な酵素活性を検出する蛍光プローブは、生命科学研究から臨床研究まで幅広い分野で活用されています。しかし蛍光プローブはその幅広い吸収・蛍光スペクトルの重なりが原因で、同時に可視化できる酵素の種類は4~5種類に限られるという課題がありました。一方でラマンイメージングではスペクトルの線幅が蛍光よりも狭いため、より多くの種類の分子を見分けて同時に検出できる手法として注目されています。我々はこれまでに酵素反応に伴ってラマン信号がOFFからONへと変化するactivatable型ラマンプローブを開発し、生細胞における酵素活性の多重検出に資するプローブ群の開発に取り組んできました(J. Am. Chem. Soc. 142, 20701-20707 (2020))。しかしながら、共鳴ラマン効果に基づくこれらのプローブでは、標的とできる分子が限定されることや安定性に課題がありました。
そこで今回我々は、色素の凝集体から強いラマン信号が観察されるという予備的知見に着目し、酵素との反応前後でプローブの凝集性が大幅に変化することで、酵素活性を検出する新たなラマンプローブの設計と開発を行いました。本プローブは、酵素との反応前は水溶液中で分散状態であり弱いラマン信号しか観察されませんが、水溶性の酵素基質部位が加水分解されることで、凝集体が生じて局所濃度が高まることで、強いラマン信号が観察されます。さらに、プローブの基質部位を変化させることで、アミノペプチダーゼやグリコシダーゼ、カルボキシペプチダーゼといった様々な酵素を標的にできること、分子内のニトリル基を同位体置換することでラマンシフト値の調整が可能であることを示しました。さらに、開発したプローブを用いて生細胞の酵素活性の検出も可能であり、異なるラマンシフト値を示すプローブを使用することで生細胞やがん細胞スフェロイドにおける複数の標的酵素を同時に可視化できることも明らかになりました。従来のラマンプローブと比較して安定性が高く、分子設計の柔軟性が高いため、さらに多様な種類の酵素活性を同時観察できるツールとして生命科学研究での応用が期待されます。
Fujioka H, Sakamoto R, Hiramatsu K, Murakami Y, Masaki M, Kawatani M, Matsumoto S, Kojima R, Urano Y, Kano H, Kamiya M*. Near-infrared coumarin-hemicyanine hybrid dyes bearing an intramolecular nucleophile for activatable fluorescence and Raman imaging. Anal. Chem. 97, 17589–17597 (2025).
【研究概要】Coumarin-Hemicyanine(CHC)ハイブリッド色素は,Coumarin由来の短波長蛍光とCHC色素全体の長波長蛍光の比を使うことで定量的な蛍光イメージングを行うことができるratio型蛍光プローブとして知られています。我々のグループではこれまでに,CHC色素に分子内求核基を導入することで分子内環化によってそのratio蛍光を制御可能なCHCプローブの開発に成功してきました(Chem. Coomun. 56, 5617–5620 (2020))。本研究では,このCHC色素にニトリル基を導入することで長波長化した4CN-CHC色素を開発しました。4CN-CHCの700 nmを超える近赤外蛍光波長は組織透過性が高く,従来型の短波長な色素と比べてより深部のイメージングに秀でていることが確認されました。また,そのratio蛍光を用いて生きた培養細胞のlysosomeの中性化を検出することに成功しました。さらに,4CN-CHCの分子内環化による波長変化は共鳴ラマン効果を利用したラマン信号のoff/onにも活用できることが見出され,ニトリル基やC=C振動のラマン信号強度をpH依存的な分子内環化によって制御可能であることが示されました。蛍光スペクトルよりもピーク幅が狭く情報量に富むラマンスペクトルの特徴を活かし,蛍光検出では難しい多重検出が可能であることも示されました。本プローブは蛍光イメージングとラマンイメージングのいずれにも特徴的な性質を有しており,生体イメージングの可能性を切り拓くプローブとして期待されます。
Nakadate M, Kojima R*, Seike N, Tachibana R, Fujita K, Tsuchiya R, Kamiya M, Plückthun A, Urano Y*. Design of Antigen-Targeting Fluorogenic Probes Utilizing Intramolecular Addition Reaction of Protein-Dye Hybrids. J. Am. Chem. Soc. 147, 30684–30693 (2025).
Ogasahara R, Mae M, Itabashi Y, Ohkubo K, Matsuura K, Shimizu H, Ban K, Togami M, Udagawa T, Fujioka H, Kamiya M, Akai S, Sawama Y. Photocatalytic and Chemoselective H/D Exchange at α-thio C(sp3)-H Bonds. J. Am. Chem. Soc. 147, 15499–15509 (2025).
Ogasahara R, Mae M, Matsuura K, Yoshimura S, Ishimoto T, Udagawa T, Harada K, Fujioka H, Kamiya M, Asada R, Uchiyama H, Tozuka Y, Akai S, Sawama Y: Photocatalytic Multiple Deuteration of Polyethylene Glycol Derivatives Using Deuterium Oxide. Chem. Eur. J. 3, e202404204 (2025).
Kunitake K, Mizuno T, Hattori K, Oneyama C, Kamiya M, Ota S, Urano Y, Kojima R: Barcoding of small extracellular vesicles with CRISPR-gRNA enables comprehensive, subpopulation-specific analysis of their biogenesis and release regulators. Nat. Commun. 15, 9777 (2024).
Sugawara K, Shin-nosuke Uno, Mako Kamiya, Akihiko Sakamoto, Yasuteru Urano, Takashi Funatsu, Kohki Okabe: Nanoscale dynamics and localization of single endogenous mRNAs in stress granules. Nucleic Acids Res. 1-12 (2024).
Tanaka H, Sugawara S, Tanaka Y, Loo T. M, Tachibana R, Abe A, Kamiya M, Urano Y, Takahashi A: Dipeptidylpeptidase-4-targeted activatable fluorescent probes visualize senescent cells. Cancer Sci. 115, 2762-2773 (2024).
Fujioka H, Murao Y, Okinaka M, Spratt SJ, Shou J, Kawatani M, Kojima R, Tachibana R, Urano Y, Ozeki Y, Kamiya M: Cyano-Hydrol green derivatives: Expanding the 9-cyanopyronin-based resonance Raman vibrational palette. Bioorg. Med. Chem. Lett. 106,129757 (2024).
【研究概要】9-cyanopyronin誘導体は共鳴ラマン効果を活用することで高い検出感度でラマンイメージングを行うことができるラマンプローブとして知られています(Nat. Commun. 12, 4518 (2021))。そのニトリル振動のラマンシフト値は色素構造のコアとなる10位の原子をO, C, Siといった原子に置換することで変化させることができますが,本研究で開発したCN-HG(cyano-hydrol green)はコアとなる原子自体を除去した構造にすることで,従来の9-cyanopyroninと比べて大きく短波数側にニトリル振動を生じさせることができました。さらに,このようなコア原子のない無架橋型構造の色素は蛍光性を有していないため,蛍光による背景信号が大きな障害となる自発ラマン散乱での検出も可能であることが確認されました。このようなユニークな特性を有するCN-HGは,ラマンイメージングの多重検出可能性をさらに拡大し,特殊なラマン顕微鏡でなくても高感度に検出することができるラマンプローブとして,生命科学研究への貢献が期待されます。
Kuriki Y, Sogawa M, Komatsu T, Kawatani M, Fujioka H, Fujita K, Ueno T, Hanaoka K, Kojima R, Hino R, Ueo H, Ueo H, Kamiya M*, Urano Y*: Modular Design Platform for Activatable Fluorescence Probes Targeting Carboxypeptidases Based on ProTide Chemistry. J. Am. Chem. Soc. 146, 521–531 (2024).[プレスリリース]
Watanabe G, Ishizawa T, Kuriki Y, Kamiya M, Ichida A, Kawaguchi Y, Akamatsu N, Kaneko J, Arita J, Kokudo N, Urano Y, Hasegawa K: Evaluation of pancreatic chymotrypsin activity for on-site prediction of clinically relevant postoperative pancreatic fistula. Pancreatology 24, 169-177 (2024).
Uchiyama H, Ban K, Nozaki S, Ikeda Y, Ishimoto T, Fujioka H, Kamiya M, Amari R, Tsujino H, Arai M, Yamazoe S, Maekawa K, Kato T, Doi M, Kadota K, Tozuka Y, Tomita N, Sajiki H, Akai S, Sawama Y: Impact of Multiple H/D Replacement on the Physicochemical Properties of Flurbiprofen. RSC Med. Chem. 14, 2583-2592 (2023).
Nanba D, Sakabe J, Mosig J, Brouard M, Toki F, Shimokawa M, Kamiya M, Braschler T, Azzabi F, Lathion SD, Johnsson K, Roy K, Schmid C, Bureau J, Rochat A, Barrandon Y: Low temperature and mTOR inhibition favor stem cell maintenance in human keratinocyte cultures. EMBO reports 24, e55439 (2023).
Takahashi R, Ishizawa T, Inagaki Y, Tanaka M, Ogasawara A, Kuriki Y, Fujita K, Kamiya M, Ushiku T, Urano Y, Hasegawa K*: Real-time fluorescence imaging to identify cholangiocarcinoma in the extrahepatic biliary tree using an enzyme-activatable probe. Liver Cancer 1-13 (2023).
Shou J, Komazawa A, Wachi Y, Kawatani M, Fujioka H, Spratt SJ, Mizuguchi T, Oguchi K, Akaboshi H, Obata F, Tachibana R, Yasunaga S, Mita Y, Misawa Y, Kojima R, Urano Y, Kamiya M*, Ozeki Y*: Super-resolution vibrational imaging based on photoswitchable Raman probe. Sci. Adv. 9, eade9118(2023). [プレスリリース]
Fujioka H, Kawatani M, Spratt S, Komazawa A, Misawa Y, Shou J, Mizuguchi T, Kosakamoto H, Kojima R, Urano Y, Obata F, Ozeki Y, Kamiya M*: Activatable Raman probes utilizing enzyme-induced aggregate formation for selective ex vivo imaging. J. Am. Chem. Soc. 145, 8871–8881 (2023).
【研究概要】ラマン散乱は蛍光と比べてスペクトル幅が狭いため,多重検出に秀でたイメージング手法として注目を集めています。しかし,ラマンイメージングに利用可能なラマンプローブの数は少なく,特に標的分子との反応前後でラマン信号強度が変化するようなactivatable型ラマンプローブの報告は極めて限定的でした。そのような中,我々のグループではこれまでに,標的酵素との反応によってラマン信号がoffからonにactivateされるラマンプローブを世界に先駆けて発表していました(J. Am. Chem. Soc. 142, 20701-20707 (2020))が,このプローブには生体組織において標的細胞のみを選択的に染色できないという課題がありました。本研究では,このような課題を克服した新規activatable型ラマンプローブの開発に成功しました。本プローブは酵素反応後に,吸収波長の長波長化に伴う前期共鳴ラマン効果の増大によってラマン信号がactivateされるのに加え,プローブの凝集体形成能もactivateされる性質があり,酵素反応後に凝集体を形成することで細胞内滞留性が向上し,酵素発現領域と非発現領域の染め分けが可能になることが明らかになりました。本プローブは様々な細胞が混在するヘテロな生体組織でも高い選択性で標的細胞領域を染色することができるため,生体組織における多重酵素活性イメージングへの応用が期待されます。[プレスリリース]
Yoshida D, Kamiya M, Kawashima S, Yoshioka T, Hino H, Abe A, Fujita K, Kojima R, Shinozaki-Ushiku A, Urano Y*, Nakajima J*: Rapid Imaging of Thymoma and Thymic Carcinoma with a Fluorogenic Probe Targeting γ-Glutamyltranspeptidase. Sci.Rep. 13, 3757 (2023).
Sawama Y*, Matsuda T, Moriyama S, Ban K, Fujioka H, Kamiya M, Shou J, Ozeki Y, Akai S, Sajiki H: Unprecedented Regioselective Deuterium-Incorporation of Alkyltrimethylammonium Chlorides and Raman Analysis. Asian J. Org. Chem. 12, e202200710 (2023).
Kawatani M, Spratt SJ, Fujioka H, Shou J, Misawa Y, Kojima R, Urano Y, Ozeki Y, Kamiya M*: 9-Cyano-10-telluriumpyronin derivatives as red-light-activatable Raman probes. Chem. Asian J. 18, e202201086 (2023).
【研究概要】光照射で信号がONになるphotoactivatable型蛍光プローブは、特定の細胞や生体分子の動態を高い時空間分解能で追跡するのに有用ですが、蛍光スペクトルは比較的幅が広いため同時に使用できるプローブの数に制限があります。一方でラマン散乱はスペクトル幅が蛍光よりも狭く、ラマンプローブを用いたイメージングにより同時に多種類の標的分子を識別可能です。したがってphotoactivatable型ラマンプローブを開発することができれば、マルチターゲットな生命現象を詳細に追跡可能となると考えられます。今回我々の研究グループでは、キサンテン10位にテルルを有する9-cyano-10-telluriumpyronin(9CN-TeP)を色素母核とした新規photoactivatable型ラマンプローブの開発に成功しました。9CN-TeP誘導体は酸化されることで吸収波長が長波長化し、前期共鳴ラマン効果によるラマン信号の増強が生じます。さらに構造展開によって安定性が向上した9CN-diMeJTePは赤色光照射によって迅速に光酸化されラマン信号が増大するphotoactivatable型ラマンプロ-ブとして機能することが明らかになりました。今後、さらに分子を改良することで、photoactivatable型ラマンプロ-ブを用いた細胞イメージング等の生命科学研究への応用が期待されます。
Imai K, Tomita N, Fujioka H, Kamiya M, Ogasahara R, Ban K, Shimizu H, Ishimoto T, Sajiki H, Akai S, Sawama Y*: Homemade Solution of NaOD in D2O: Applications in the Field of Stilbene-d1 Synthesis. Asian J. Org. Chem. 12, e202200690 (2023).
Koda K, Keller S, Kojima R, Kamiya M*, and Urano Y* : Measuring the pH of Acidic Vesicles in Live Cells with an Optimized Fluorescence Lifetime Imaging Probe. Anal. Chem. 94, 11264–11271 (2022).
Kawashima S, Yoshida D, Yoshioka T, Ogasawara A, Fujita K, Yanagiya M, Nagano M, Konoeda C, Hino H, Kitano K, Sato M, Hino R, Kojima R, Komatsu T, Kamiya M, Urano Y*, Nakajima J*. Rapid imaging of lung cancer using a red fluorescent probe to detect dipeptidyl peptidase 4 and puromycin-sensitive aminopeptidase activities. Sci. Rep. 12, 9100 (2022).
Kuriki Y, Yoshioka T, Kamiya M*, Komatsu T, Takamaru H, Fujita K, Iwaki H, Nanjo A, Akagi Y, Takeshita K, Hino H, Hino R, Kojima R, Ueno T, Hanaoka K, Abe S, Saito Y, Nakajima J, Urano Y*: Development of a fluorescent probe library enabling efficient screening of tumour-Imaging probes based on discovery of biomarker enzymatic activities. Chem. Sci. 13, 4474-4481 (2022). (Selected as “Front Cover“)
Nakada A, Maruyama T, Kamiya M, Hanaoka K, Urano Y*: Rapid Visualization of Deeply Located Tumors In Vivo by Intravenous Administration of a g-Glutamyltranspeptidase-Activated Fluorescent Probe. Bioconjug Chem. 33, 523–529 (2022).
Hirose Y, Uchida M, Tsuboi M, Nakagawa T, Yaga L, Maeda S, Momoi Y, Kuriki Y, Kamiya M, Urano Y, Yonezawa T*: Rapid visualization of mammary gland tumor lesions of dogs using the enzyme-activated fluorogenic probe; γ-glutamyl hydroxymethyl rhodamine green. J. Vet. Med. Sci. 84, 593-599 (2022).
Sakai K, Kondo Y, Fujioka H, Kamiya M, Aoki K*, Goto Y*: Near-infrared imaging in fission yeast using a genetically encoded phycocyanobilin biosynthesis system. J. Cell. Sci. 134, jcs259315 (2021).
Takagi T, Ueno T*, Ikawa K, Asanuma D, Nomura Y, Uno SN, Komatsu T, Kamiya M, Hanaoka K, Okimura C, Iwadate Y, Hirose K, Nagano T, Sugimura K, Urano Y*: Discovery of an F-actin-binding small molecule serving as a fluorescent probe and a scaffold for functional probes. Sci. Adv. 7, eabg8585 (2021).
Ogawa S, Kubo H*, Murayama Y, Kubota T, Yubakami M, Matsumoto T, Yamamoto Y, Morimura R, Ikoma H, Okamoto K, Kamiya M, Urano Y, Otsuji E: Rapid fluorescence imaging of human hepatocellular carcinoma using the β-galactosidase-activatable fluorescence probe SPiDER-βGal. Sci. Rep. 11, 17946 (2021).
Takahashi R, Ishizawa T, Sato M, Inagaki Y, Takanka M, Kuriki Y, Kamiya M, Ushiku T, Urano Y, Hasegawa K*: Fluorescence Imaging Using Enzyme-Activatable Probes for Real-Time Identification of Pancreatic Cancer. Front. Oncol. 11, 714527 (2021).
Iwaki H, Kamiya M*, Kawatani M, Kojima R, Yamasoba T, Urano Y*: Fluorescence Probes for Imaging Basic Carboxypeptidase Activity in Living Cells with High Intracellular Retention. Anal. Chem. 93, 3470-3476 (2021).
Takahashi H, Kamiya M, Kawatani M, Umezawa K, Ukita Y, Niwa S, Oda T*, Urano Y*: Neural and behavioral control in Caenorhabditis elegans by a yellow-light-activatable caged compound. Proc. Natl. Acad. Sci. USA. 118, e2009634118 (2021).
Obara R, Kamiya M*, Tanaka Y, Abe A, Kojima R, Kawaguchi T, Sugawara M, Takahashi A, Noda T, Urano Y*: γ-Glutamyltranspeptidase (GGT)-Activatable Fluorescence Probe for Durable Tumor Imaging. Angew. Chem. Int. Ed. 60, 2125-2129 (2021).
Kashima H, Kamiya M*, Obata F, Kojima R, Nakano S, Miura M, Urano Y*: Photoactivatable fluorophores for durable labelling of individual cells. Chem. Commun. 57, 5802-5805 (2021).
Kitagawa Y, Tanaka S*, Kamiya M, Kuriki Y, Yamamoto K, Shimizu T, Nejo T, Hana T, Matsuura R, Koike T, Yamazawa E, Kushihara Y, Takahashi S, Nomura M, Takami H, Takayanagi S, Mukasa A, Urano Y*, Saito N: A novel topical fluorescent probe for detection of glioblastoma. Clin. Cancer Res. 27, 3936–3947 (2021).
Kubo H, Murayama Y*, Ogawa S, Matsumoto T, Yubakami M, Ohashi T, Kubota T, Okamoto K, Kamiya M, Urano Y, Otsuji E: b-Galactosidase is a target enzyme for detecting peritoneal metastasis of gastric cancer. Sci. Rep. 11, 10664 (2021).
Fujioka H, Shou J, Kojima R, Urano Y, Ozeki Y*, Kamiya M*. Multicolor Activatable Raman Probes for Simultaneous Detection of Plural Enzyme Activities. J. Am. Chem. Soc. 142, 20701-20707 (2020).
Morozumi A, Kamiya M*, Uno SN, Umezawa K, Kojima R, Yoshihara T, Tobita S, Urano Y*. Spontaneously Blinking Fluorophores Based on Nucleophilic Addition/Dissociation of Intracellular Glutathione for Live-Cell Superresolution Imaging. J. Am. Chem. Soc. 142, 9625-9633 (2020).
Asano T, Nagayo Y, Tsuda S, Ito A, Kobayashi W, Fujita K, Sato K, Nishiguchi KM, Kunikata H, Fujioka H, Kamiya M, Urano Y, Nakazawa T*. Companion Diagnosis for Retinal Neuroprotective Treatment by Real-Time Imaging of Calpain Activation Using a Novel Fluorescent Probe. Bioconjug. Chem. 31, 2241–2251 (2020).
Tachibana R, Kamiya M*, Morozumi A, Miyazaki Y, Fujioka H, Nanjo A, Kojima R, Komatsu T, Ueno T, Hanaoka K, Yoshihara T, Tobita S, Urano Y*: Design of spontaneously blinking fluorophores for live-cell super-resolution imaging based on quantum-chemical calculations. Chem. Commun. 56, 13173-13176 (2020).
Kawashima S, Yoshioka T, Hino H, Kitano K, Nagayama K, Sato M, Kojima R, Kamiya M, Urano Y, Nakajima J*: ɤ-glutamyl hydroxymethyl rhodamine green fluorescence as a prognostic indicator for lung cancer. Gen. Thorac. Cardiovasc. Surg. 68,1418-1424 (2020).
Tachibana R, Kamiya M, Suzuki S, Morokuma K, Nanjo A, Urano Y*: Molecular design strategy of fluorogenic probes based on quantum chemical prediction of intramolecular spirocyclization. Commun. Chem. 3, 82 (2020).
Kono Y, Ishizawa T, Kokudo N, Kuriki Y, Iwatate RJ, Kamiya M, Urano Y, Kumagai A, Kurokawa H, Miyawaki A*, Hasegawa K*. On-Site Monitoring of Postoperative Bile Leakage Using Bilirubin-Inducible Fluorescent Protein. World J. Surg. 44, 45-4253 (2020).
Fujioka H, Uno SN, Kamiya M, Kojima R, Johnsson K*, Urano Y*. Activatable fluorescent probes for hydrolase enzymes based on coumarin-hemicyanine hybrid fluorophores with large Stokes shifts. Chem. Commun. 56, 5617-5620 (2020).
Fujita K, Kamiya M, Yoshioka T, Ogasawara A, Hino R, Kojima R, Ueo H, Urano Y*. Rapid and Accurate Visualization of Breast Tumors with a Fluorescent Probe Targeting α-Mannosidase 2C1. ACS Cent. Sci. 6, 2217-2227 (2020).
Yamamoto K, Ohnishi S*, Mizushima T, Kodaira J, Ono M, Hatanaka Y, Hatanaka KC, Kuriki Y, Kamiya M, Ehira N, Shinada K, Takahashi H, Shimizu Y, Urano Y, Sakamoto N. Detection of early adenocarcinoma of the esophagogastric junction by spraying an enzyme-activatable fluorescent probe targeting Dipeptidyl peptidase-IV. BMC Cancer. 20, 64 (2020).
Iwatate RJ, Yoshinari A, Yagi N, Grzybowski M, Ogasawara H, Kamiya M, Komatsu T, Taki M, Yamaguchi S, Frommer WB, Nakamura M*. Covalent Self-Labeling of Tagged Proteins with Chemical Fluorescent Dyes in BY-2 Cells and Arabidopsis Seedlings. Plant Cell. 32, 3081-3094 (2020).
Rivas C, Kamiya M*, Urano Y*: A novel sialidase-activatable fluorescence probe with improved stability for the sensitive detection of sialidase. Bioorg. Med. Chem. Lett. 30, 126860 (2020).
Chiba M, Kamiya M*, Tsuda-Sakurai K, Fujisawa Y, Kosakamoto H, Kojima R, Miura M, Urano Y*: Activatable Photosensitizer for Targeted Ablation of lacZ-Positive Cells with Single-Cell Resolution. ACS Cent. Sci. 5, 1676-1681 (2019).
Yamamoto K, Kamiya M, Urano Y*: Highly sensitive fluorescence imaging of cancer with avidin-protease probe conjugate. Bioorg. Med. Chem. Lett. 9, 126663 (2019).
Kitagawa Y, Tanaka S*, Kuriki Y, Yamamoto K, Ogasawara A, Nejo T, Matsuura R, Koike T, Hana T, Takahashi S, Nomura M, Takayanagi S, Mukasa A, Kamiya M, Urano Y, Saito N: Spray Fluorescent Probes for Fluorescence-Guided Neurosurgery. Front Oncol. 9, 727 (2019).
Kawatani M, Yamamoto K, Yamada D, Kamiya M*, Miyakawa J, Miyama Y, Kojima R, Morikawa T, Kume H, Urano Y*: Fluorescence Detection of Prostate Cancer by an Activatable Fluorescence Probe for PSMA Carboxypeptidase Activity. J. Am. Chem. Soc. 14, 10409-10416 (2019).
Ogasawara A, Kamiya M, Sakamoto K, Kuriki Y, Fujita K, Komatsu T, Ueno T, Hanaoka K, Onoyama H, Abe H, Tsuji Y, Fujishiro M, Koike K, Fukayama M, Seto Y, Urano Y*: Red Fluorescence Probe Targeted to Dipeptidylpeptidase-IV for Highly Sensitive Detection of Esophageal Cancer. Bioconjug. Chem. 30, 1055-1060 (2019).
Ito H, Kawamata Y, Kamiya M*, Tsuda-Sakurai K, Tanaka S, Ueno T, Komatsu T, Hanaoka K, Okabe S, Miura M, Urano Y*: Red-Shifted Fluorogenic Substrate for Detection of lacZ-Positive Cells in Living Tissue with Single-Cell Resolution. Angew. Chem. Int. Ed. 57, 15702-15706 (2018).
Moriizumi Y, Tabata KV, Watanabe R, Doura T, Kamiya M, Urano Y, Noji H*: Hybrid cell reactor system from Escherichia coli protoplast cells and arrayed lipid bilayer chamber device. Sci. Rep. 8, 11757 (2018).
Umezawa K, Kamiya M*, Urano Y*: A reversible fluorescent probe for real-time live-cell imaging and quantification of endogenous hydropolysulfides. Angew. Chem. Int. Ed. 57, 9346-9350 (2018).
Kuriki Y, Kamiya M, Kubo H, Komatsu T, Ueno T, Tachibana R, Hayashi K, Hanaoka K, Yamashita S, Ishizawa T, Kokudo N, Urano Y*: Establishment of Molecular Design Strategy To Obtain Activatable Fluorescent Probes for Carboxypeptidases. J. Am. Chem. Soc. 140, 1767-1773 (2018).
Iwatate RJ, Kamiya M*, Umezawa K, Kashima H, Nakadate M, Kojima R, Urano Y*: Silicon Rhodamine-Based Near-Infrared Fluorescent Probe for γ-Glutamyltransferase. Bioconjug. Chem. 29, 241-244 (2018).
Uno S, Kamiya M*, Morozumi A, Urano Y*: A green-light-emitting, spontaneously blinking fluorophore based on intramolecular spirocyclization for dual-colour super-resolution imaging. Chem. Comm. 54, 102-105 (2018).
Kawatani M, Kamiya M, Takahashi H, Urano Y*: Factors affecting the uncaging efficiency of 500nm light-activatable BODIPY caging group. Bioorg. Med. Chem. Lett. 28, 1-5 (2018).
Tabe H, Sukenobe K, Kondo T, Sakurai A, Maruo M, Shimauchi A, Hirano M, Uno SN, Kamiya M, Urano Y, Matsushita M, Fujiyoshi S*: Cryogenic Fluorescence Localization Microscopy of Spectrally Selected Individual FRET Pairs in a Water Matrix. J. Phys. Chem. B. 122, 6906-6911 (2018).
Mizushima T, Ohnishi S*, Shimizu Y, Hatanaka Y, Hatanaka KC, Kuriki Y, Kamiya M, Homma A, Yamamoto K, Ono S, Urano Y, Sakamoto N: Rapid detection of superficial head and neck squamous cell carcinoma by topically spraying fluorescent probe targeting dipeptidyl peptidase-IV. Head Neck. 40, 1466-1475 (2018).
Ida S, Hiki N*, Ishizawa T, Kuriki Y, Kamiya M, Urano Y, Nakamura T, Tsuda Y, Kano Y, Kumagai K, Nunobe S, Ohashi M, Sano T: Pancreatic Compression during Lymph Node Dissection in Laparoscopic Gastrectomy: Possible Cause of Pancreatic Leakage. J. Gastric Cancer. 8, 134-141 (2018).
Hirasawa T, Iwatate RJ, Kamiya M, Okawa S, Fujita M, Urano Y, Ishihara M*: Spectral-differential-based unmixing for multispectral photoacoustic imaging. Appl. Opt. 57, 2383-2393 (2018).
Okubo K, Kurosawa M, Kamiya M, Urano Y, Suzuki A, Yamamoto K, Hase K, Homma K, Sasaki J, Miyauchi H, Hoshino T, Hayashi M, Mayadas TN, Hirahashi J*: Macrophage extracellular trap formation promoted by platelet activation is a key mediator of rhabdomyolysis-induced acute kidney injury. Nat. Med. 24, 232-238 (2018).
Shiratori T, Kyumoto-Nakamura Y, Kukita A, Uehara N, Zhang J, Koda K, Kamiya M, Badawy T, Tomoda E, Xu X, Yamaza T, Urano Y, Koyano K, Kukita T: IL-1β Induces Pathologically Activated Osteoclasts Bearing Extremely High Levels of Resorbing Activity: A Possible Pathological Subpopulation of Osteoclasts, Accompanied by Suppressed Expression of Kindlin-3 and Talin-1. J. Immunol. 200, 218-228 (2018).
Yogo T, Umezawa K, Kamiya M, Hino R, Urano Y*: Development of an Activatable Fluorescent Probe for Prostate Cancer Imaging. Bioconjug. Chem. 28, 2069-2076 (2017).
Miyata Y, Ishizawa T, Kamiya M, Yamashita S, Hasegawa K, Ushiku A, Shibahara J, Fukayama M, Urano Y*, Kokudo N*: Intraoperative imaging of hepatic cancers using γ-glutamyltranspeptidase-specific fluorophore enabling real-time identification and estimation of recurrence. Sci. Rep. 7, 3542 (2017).
Chiba M, Ichikawa Y, Kamiya M, Komatsu T, Ueno T, Hanaoka K, Nagano T, Lange N, Urano Y*: An Activatable Photosensitizer Targeted to γ-Glutamyltranspeptidase. Angew. Chem. Int. Ed. 56, 10418-10422 (2017).
Takakura H, Zhang Y, Erdmann SR, Thompson DA, Lin Y, McNellis B, Rivera-Molina F, Uno S, Kamiya M, Urano Y, Rothman EJ, Bewersdorf J, Schepartz A*, Toomre D*: Long time-lapse nanoscopy with spontaneously blinking membrane probes. Nat. Biotech. 35, 773-780 (2017).
Onagi J, Komatsu T*, Ichihashi Y, Kuriki Y, Kamiya M, Terai T, Ueno T, Hanaoka K, Matsuzaki H, Hata K, Watanabe T, Nagano T, Urano Y*: Discovery of Cell-Type-Specific and Disease-Related Enzymatic Activity Changes via Global Evaluation of Peptide Metabolism. J. Am. Chem. Soc. 139, 3465-3472 (2017).
Umezawa K, Yoshida M, Kamiya M*, Yamasoba T, Urano Y*: Rational design of reversible fluorescent probes for live-cell imaging and quantification of fast glutathione dynamics. Nat. Chem. 9: 279–286 (2017).
Doura T, Kamiya M*, Obata F, Yamaguchi Y, Hiyama TY, Matsuda T, Fukamizu A, Noda M, Miura M, Urano Y*: Detection of LacZ-Positive Cells in Living Tissue with Single-Cell Resolution. Angew. Chem. Int. Ed. 55, 9620-9624 (2016).
Okubo K, Kamiya M, Urano Y, Nishi H, Herter JM, Mayadas T, Hirohama D, Suzuki K, Kawakami H, Tanaka M, Kurosawa M, Kagaya S, Hishikawa K, Nangaku M, Fujita T, Hayashi M, Hirahashi J*: Lactoferrin Suppresses Neutrophil Extracellular Traps Release in Inflammation. EBioMedicine. 10, 204-15 (2016).
Shinden Y, Ueo H, Tobo T, Gamachi A, Utou M, Komatsu H, Nambara S, Saito T, Ueda M, Hirata H, Sakimura S, Takano Y, Uchi R, Kurashige J, Akiyoshi S, Iguchi T, Eguchi H, Sugimachi K, Kubota Y, Kai Y, Shibuta K, Kijima Y, Yoshinaka H, Natsugoe S, Mori M, Maehara Y, Sakabe M, Kamiya M, Kakareka JW, Pohida TJ, Choyke PL, Kobayashi H, Ueo H, Urano Y*, Mimori K*: Rapid diagnosis of lymph node metastasis in breast cancer using a new fluorescent method with γ-glutamyl hydroxymethyl rhodamine green. Sci. Rep. 6, 27525 (2016).
Onoyama H, Kamiya M, Kuriki Y, Komatsu T, Abe H, Tsuji Y, Yagi K, Yamagata Y, Aikou S, Nishida M, Mori K, Yamashita H, Fujishiro M, Nomura S, Shimizu N, Fukayama M, Koike K, Urano Y*, Seto Y*: Rapid and sensitive detection of early esophageal squamous cell carcinoma with fluorescence probe targeting dipeptidylpeptidase IV. Sci. Rep. 6, 26399 (2016).
Hino H, Kamiya M, Kitano K, Mizuno K, Tanaka S, Nishiyama N, Kataoka K, Urano Y*, Nakajima J*: Rapid Cancer Fluorescence Imaging Using A γ-Glutamyltranspeptidase-Specific Probe For Primary Lung Cancer. Transl. Oncol. 9, 203-210 (2016).
Matsuzaki H, Kamiya M, Iwatate RJ, Asanuma D, Watanabe T*, Urano Y*: Novel Hexosaminidase-Targeting Fluorescence Probe for Visualizing Human Colorectal Cancer. Bioconjug. Chem. 27, 973-81 (2016).
Mizushima T, Ohnishi S*, Shimizu Y, Hatanaka Y, Hatanaka KC, Hosono H, Kubota Y, Natsuizaka M, Kamiya M, Ono S, Homma A, Kato M, Sakamoto N, Urano Y: Fluorescent imaging of superficial head and neck squamous cell carcinoma using a γ-glutamyltranspeptidase-activated targeting agent: a pilot study. BMC Cancer 16, 411 (2016).
Hattori M, Kawamura G, Kojima R, Kamiya M, Urano Y, Ozawa T*: Confocal Bioluminescence Imaging for Living Tissues with a Caged Substrate of Luciferin. Anal. Chem. 88, 6231-8 (2016).
Kawakubo K, Ohnishi S*, Hatanaka Y, Hatanaka KC, Hosono H, Kubota Y, Kamiya M, Kuwatani M, Kawakami H, Urano Y*, Sakamoto N: Feasibility of Using an Enzymatically Activatable Fluorescence Probe for the Rapid Evaluation of Pancreatic Tissue Obtained Using Endoscopic Ultrasound-Guided Fine Needle Aspiration: a Pilot Study. Mol. Imaging Biol. 18, 463-71 (2016).
Kitakaze K, Mizutani Y, Sugiyama E, Tasaki C, Tsuji D, Maita N, Hirokawa T, Asanuma D, Kamiya M, Sato K, Setou M, Urano Y, Togawa T, Otaka A, Sakuraba H, Itoh K*: Protease-resistant modified human β-hexosaminidase B ameliorates symptoms in GM2 gangliosidosis model. J. Clin. Invest. 126, 1691-703 (2016).
Shimane T*, Aizawa H, Koike T, Kamiya M, Urano Y, Kurita H: Oral cancer intraoperative detection by topically spraying a γ-glutamyl transpeptidase-activated fluorescent probe. Oral Oncol. 54, e16-8 (2016).
Hayashi A, Asanuma D, Kamiya M, Urano Y, Okabe S*: High affinity receptor labeling based on basic leucine zipper domain peptides conjugated with pH-sensitive fluorescent dye: Visualization of AMPA-type glutamate receptor endocytosis in living neurons. Neuropharmacol. 100, 66-75 (2016).
Iwatate RJ, Kamiya M, Urano Y*: Asymmetric Rhodamine-Based Fluorescence Probes for Multi-colour In Vivo Imaging. Chem-Eur. J. 22, 1696-1703 (2015).
Anraku Y, Kishimura A, Kamiya M, Tanaka S, Nomoto T, Toh K, Matsumoto Y, Fukushima S, Sueyoshi D, Kano MR, Urano Y, Nishiyama N, Kataoka K*: Systemically Injectable Enzyme-Loaded Polyion Complex Vesicles as In Vivo Nanoreactors Functioning in Tumors. Angew. Chem. Int. Ed. 55, 560-5 (2016).
Kamiya M, Urano Y: Rapid and sensitive fluorescent imaging of tiny tumors in vivo and in clinical specimens. Curr. Opin. Chem. Biol. 33, 9-15 (2016).
Hirabayashi K, Hanaoka K, Takayanagi T, Toki Y, Egawa T, Kamiya M, Komatsu T, Ueno T, Terai T, Yoshida K, Uchiyama M, Nagano T, Urano Y*: Analysis of Chemical Equilibrium of Silicon-Substituted Fluorescein and Its Application to Develop a Scaffold for Red Fluorescent Probes. Anal. Chem. 87, 9061-9 (2015).
Ueo H, Shinden Y, Tobo T, Gamachi A, Udo M, Komatsu H, Nambara S, Saito T, Ueda M, Hirata H, Sakimura S, Takano Y, Uchi R, Kurashige J, Akiyoshi S, Iguchi T, Eguchi H, Sugimachi K, Kubota Y, Kai Y, Shibuta K, Kijima Y, Yoshinaka H, Natsugoe S, Mori M, Maehara Y, Sakabe M, Kamiya M, Kakareka JW, Pohida TJ, Choyke PL, Kobayashi H, Ueo H, Urano Y*, Mimori K*: Rapid intraoperative visualization of breast lesions with γ-glutamyl hydroxymethyl rhodamine green. Sci. Rep. 5, 12080 (2015).
Uno S, D.K.Tiwari, Kamiya M, Arai Y, Nagai T*, Urano Y*: A guide to use photocontrollable fluorescent proteins and synthetic smart fluorophores for nanoscopy. Microscopy 64, 263-77 (2015).
Asanuma D, Sakabe M, Kamiya M, Yamamoto K, Hiratake J, Ogawa M, Kosaka N, Choyke PL, Nagano T, Kobayashi H, Urano Y*: Sensitive β-galactosidase-targeting fluorescence probe for visualizing small peritoneal metastatic tumours in vivo. Nat. Comm. 6, 6463 (2015).
Hirakawa Y, Yoshihara T, Kamiya M, Mimura I, Fujikura D, Masuda T, Kikuchi R, Takahashi I, Urano Y, Tobita S, Nangaku M*: Quantitating intracellular oxygen tension in vivo by phosphorescence lifetime measurement. Sci. Rep. 5, 17838 (2015).
Kojima R, Takakura H, Kamiya M, Kobayashi E, Komatsu T, Ueno T, Terai T, Hanaoka K, Nagano T, Urano Y*: Development of a Sensitive Bioluminogenic Probe for Imaging Highly Reactive Oxygen Species in Living Rats. Angew. Chem. Int. Ed. 54, 14768-71 (2015).
Mori K, Ishizawa T*, Yamashita S, Kamiya M, Urano Y, Kokudo N: Intraoperative visualization of pancreatic juice leaking from the pancreatic stump in a swine model. Gastroenterology 149, 1334-6 (2015).
Takakura H, Kojima R, Kamiya M, Kobayashi E, Komatsu T, Ueno T, Terai T, Hanaoka K, Nagano T, Urano Y*: New Class of Bioluminogenic Probe Based on Bioluminescent Enzyme-Induced Electron Transfer: BioLeT. J. Am. Chem. Soc. 137, 4010-4013 (2015).
Sato C, Abe S*, Saito Y, So Tsuruki E, Takamaru H, Makazu M, Sato Y, Sasaki H, Tanaka H, Ikezawa N, Yamada M, Sakamoto T, Nakajima T, Matsuda T, Kushima R, Kamiya M, Maeda S, Urano Y*: A pilot study of fluorescent imaging of colorectal tumors using a γ-glutamyl-transpeptidase-activatable fluorescent probe. Digestion. 91, 70-6 (2015).
Miyata A, Ishizawa T*, Kamiya M, Shimizu A, Kaneko J, Ijichi H, Shibahara J, Fukayama M, Midorikawa Y, Urano Y, Kokudo N: Photoacoustic tomography of human hepatic malignancies using intraoperative indocyanine green fluorescence imaging. PLOS One 9, e112667 (2014).
Fujii T, Kamiya M, Urano Y*: In Vivo Imaging of Intraperitoneally Disseminated Tumors in Model Mice by Using Activatable Fluorescent Small-Molecular Probes for Activity of Cathepsins. Bioconjug. Chem. 25, 1838-46 (2014).
Umeda N, Takahashi H, Kamiya M, Ueno T, Komatsu T, Terai T, Hanaoka K, Nagano T, Urano Y*: Boron dipyrromethene as a fluorescent caging group for single-photon uncaging with long-wavelength visible light. ACS Chem. Biol. 9, 2242-2246 (2014).
Yoshida M, Kamiya M, Yamasoba T, Urano Y*: A highly sensitive, cell-membrane-permeable fluorescent probe for glutathione. Bioorg. Med. Chem. Lett. 24, 4363-6 (2014).
Uno S, Kamiya M*, Yoshihara T, Sugawara K, Okabe K, Tarhan M C, Fujita H, Funatsu T, Okada Y, Tobita S and Urano Y*: A spontaneously blinking fluorophore based on intramolecular spirocyclization for live-cell super-resolution imaging. Nat. Chem. 6, 681–689 (2014).
Ichikawa Y, Kamiya M, Obata F, Miura M, Terai T, Komatsu T, Ueno T, Hanaoka K, Nagano T, Urano Y*: Selective Ablation of β-Galactosidase-Expressing Cells with a Rationally Designed Activatable Photosensitizer. Angew. Chem. Int. Ed. 53, 6772-6775 (2014).
Asanuma D, Takaoka Y, Namiki S, Takikawa K, Kamiya M, Nagano T, Urano Y, Hirose K.*: Acidic-pH-Activatable Fluorescence Probes for Visualizing Exocytosis Dynamics. Angew. Chem. Int. Ed. 53, 6085-6089 (2014).
Abo M, Minakami R, Miyano K, Kamiya M, Nagano T, Urano Y, Sumimoto H*: Visualization of Phagosomal Hydrogen Peroxide Production by A Novel Fluorescent Probe That Is Localized via SNAP-tag Labeling. Anal. Chem. 86, 5983-90 (2014).
Watanabe R, Soga N, Fujita D, Tabata KV, Yamauchi L, Hyeon Kim S, Asanuma D, Kamiya M, Urano Y, Suga H, Noji H*: Arrayed lipid bilayer chambers allow single-molecule analysis of membrane transporter activity. Nat. Commun. 5, 4519 (2014).
Arai HC, Yukawa A, Iwatate RJ, Kamiya M, Watanabe R, Urano Y, Noji H*: Torque generation mechanism of F1-ATPase upon NTP binding. Biophys J. 107, 156-64 (2014).
Sakabe M, Asanuma D, Kamiya M, Iwatate RJ, Hanaoka K, Terai T, Nagano T, Urano Y*: Rational design of highly sensitive fluorescence probes for protease and glycosidase based on precisely controlled spirocyclization. J. Am. Chem. Soc. 135, 409-414 (2013).
Kobayashi T, Komatsu T, Kamiya M, Campos C, González-Gaitán M, Terai T, Hanaoka K, Nagano T, Urano Y*: Highly activatable and environment-insensitive optical highlighters for selective spatiotemporal imaging of target proteins. J. Am. Chem. Soc. 134, 11153-11160 (2012).
Campos C, Kamiya M, Banala S, Johnsson K*, González-Gaitán M*: Labelling cell structures and tracking cell lineage in zebrafish using SNAP-tag. Dev. Dyn. 240, 820-7 (2011).
Urano Y*, Sakabe M, Kosaka N, Ogawa M, Mitsunaga M, Asanuma D, Kamiya M, Young M R, Nagano T, Choyke P L, Kobayashi H*: Rapid cancer detection by topically spraying a γ-glutamyltranspeptidase-activated fluorescent probe. Sci. Transl. Med. 3, 110ra119 (2011).
Kamiya M, Asanuma D, Kuranaga E, Takeishi A, Sakabe M, Miura M, Nagano T*, Urano Y*: β-Galactosidase fluorescence probe with improved cellular accumulation based on a spirocyclized rhodol scaffold. J. Am. Chem. Soc. 133, 12960-12963 (2011).
Kamiya M, Johnsson K*: Localizable and highly sensitive calcium indicator based on a BODIPY fluorophore. Anal. Chem. 82, 6472-6479 (2010).
Yogo T, Urano Y, Kamiya M, Sano K, Nagano T*: Development of enzyme-activated photosensitizer based on intramolecular electron transfer. Bioorg. Med. Chem. Lett. 20, 4320-4323 (2010).
Urano Y*, Asanuma D, Hama Y, Koyama Y, Barrett T, Kamiya M, Nagano T, Watanabe T, Hasegawa A, Choyke P L, Kobayashi H*: Selective molecular imaging of viable cancer cells with pH-activatable fluorescence probes. Nat. Med. 15, 104-109 (2009).
Kamiya M, Kobayashi H, Hama Y, Koyama Y, Bernardo M, Nagano T, Choyke P L, Urano Y*: An enzymatically activated fluorescence probe for targeted tumor imaging. J. Am. Chem. Soc. 129, 3918-3929 (2007).
Kobayashi T, Urano Y, Kamiya M, Ueno T, Kojima H, Nagano T*: Highly activatable and rapidly releasable caged fluorescein derivatives. J. Am. Chem. Soc. 129, 6696-6697(2007).
Hama Y, Urano Y, Koyama Y, Kamiya M, Bernardo M, Paik R S, Shin I S, Paik C H, Choyke P L, Kobayashi H*: A target cell-specific activatable fluorescence probe for in vivo molecular imaging of cancer based on a self-quenched avidin-rhodamine conjugate. Cancer Res. 67, 2791-2799 (2007).
Komatsu T, Kikuchi K, Takakusa H, Hanaoka K, Ueno T, Kamiya M, Urano Y, Nagano T*: Design and synthesis of an enzyme activity-based labeling molecule with fluorescence spectral change. J. Am. Chem. Soc. 128, 15946-15947 (2006).
Hama Y, Urano Y, Koyama Y, Kamiya M, Bernardo M, Paik R S, Krishna M C, Choyke P L, Kobayashi H*: In vivo spectral fluorescence imaging of submillimeter peritoneal cancer implants using a lectin-targeted optical agent. Neoplasia 8, 607-612 (2006).
Kamiya M, Urano Y, Ebata N, Yamamoto M, Kosuge J, Nagano T*: Extension of the applicable range of fluorescein: a fluorescein-based probe for Western blot analysis. Angew. Chem. Int. Ed. 44, 5439-5441 (2005).
Urano Y, Kamiya M, Kanda K, Ueno T, Hirose K, Nagano T*: Evolution of fluorescein as a platform for finely tunable fluorescence probes. J. Am. Chem. Soc. 127, 4888-4894 (2005).
・藤岡礼任,神谷真子、機能性ラマンイメージングプローブの開発
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・藤岡礼任,神谷真子、Activatable型ラマンプローブを用いる酵素活性イメージング
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・ 月刊「細胞」2022年12月号(ニューサイエンス社) (2022/11/22)
・神谷真子、光学と化学によるラマンイメージングの新機軸(総論)
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Staff
・2025.4.8 神谷真子教授、第2回神戸賞Young Investigator賞
・2024.10.9 神谷真子教授、バイオインダストリー奨励賞
・2023.12.6 神谷真子教授、島津奨励賞
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Lab member
・2025.6.6 金井駿介(M1)、日本ケミカルバイオロジー学会第19回年会、ポスター賞
・2025.3.21 金井駿介(B4)、学士特定課題研究発表会・優秀発表賞
・2025.2.27 金井駿介(B4)、令和6年度高宮賞
・2023.12.1 村尾 侑大(M1)、 修士論文研究計画論第二・中間発表会、優秀ポスター賞
・2023.3.7 村尾 侑大(B3)、令和4年度高宮賞
・Science Advancesに掲載された光スイッチングラマンプローブの論文 (DOI: 10.1126/sciadv.ade9118) に関するプレスリリース
※2023.6.23.の化学工業日報(朝刊)本研究の紹介記事が掲載
・J. Am. Chem. Soc. に掲載された凝集誘導型のラマンプローブの論文(doi: 10.1021/jacs.2c12381) に関するプレスリリース
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