Hanaoka, Kenjiro

写真a

Affiliation

Faculty of Pharmacy, Department of Pharmaceutical Sciences Analytical Chemistry for Drug Discovery (Shiba-Kyoritsu)

Position

Professor

E-mail Address

E-mail address

Related Websites

External Links

Career 【 Display / hide

  • 2005.04
    -
    2006.03

    日本学術振興会特別研究員(PD)

  • 2005.12
    -
    2007.03

    University of Texas, Southwestern Medical Center, 博士研究員

  • 2006.04
    -
    2007.03

    日本学術振興会特別研究員(SPD)

  • 2007.04
    -
    2010.03

    東京大学, 大学院薬学系研究科, 助教

  • 2010.04
    -
    2011.10

    東京大学, 大学院薬学系研究科, 講師

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Academic Background 【 Display / hide

  • 1996.04
    -
    2000.03

    The University of Tokyo, 薬学部, 薬学科

    Graduated

  • 2000.04
    -
    2002.03

    The University of Tokyo, 大学院薬学系研究科

    Completed, Master's course

  • 2002.04
    -
    2005.03

    The University of Tokyo, 大学院薬学系研究科

    Completed, Doctoral course

Academic Degrees 【 Display / hide

  • 博士(薬学), The University of Tokyo, 2005.03

Licenses and Qualifications 【 Display / hide

  • 薬剤師免許, 2000.07

  • 第一種衛生管理, 2012.02

 

Research Areas 【 Display / hide

  • Bio-related chemistry (Chemical Biology)

  • Chemical biology (Molecular Imaging)

  • Drug development chemistry (Drug DIscovery Chemistry)

Research Themes 【 Display / hide

  • 生命現象の可視化/制御を目指した機能性分子の創製, 

    1999.04
    -
    Present

 

Books 【 Display / hide

  • Development of a small-molecule-based activatable photoacoustic probe

    Ikeno T., Hanaoka K., Urano Y., Methods in Enzymology, 2021.01

     View Summary

    Photoacoustic (PA) imaging is an emerging imaging modality that combines the advantages of optical imaging and ultrasound imaging. In particular, activatable PA probes, which visualize the presence or the activity of target molecules in terms of a change of the PA signal, are useful tools for functional imaging. In this chapter, we describe the development of small-molecule-based activatable PA probes, focusing on the design and synthesis of PA-MMSiNQ, our recently developed activatable PA probe for HOCl. We also describe the protocols used for evaluation of PA-MMSiNQ with a UV–vis spectrometer and a PA imaging microscope.

Papers 【 Display / hide

  • Sulfide catabolism ameliorates hypoxic brain injury

    Marutani E., Morita M., Hirai S., Kai S., Grange R.M.H., Miyazaki Y., Nagashima F., Traeger L., Magliocca A., Ida T., Matsunaga T., Flicker D.R., Corman B., Mori N., Yamazaki Y., Batten A., Li R., Tanaka T., Ikeda T., Nakagawa A., Atochin D.N., Ihara H., Olenchock B.A., Shen X., Nishida M., Hanaoka K., Kevil C.G., Xian M., Bloch D.B., Akaike T., Hindle A.G., Motohashi H., Ichinose F.

    Nature Communications (Nature Communications)  12 ( 1 ) 3108 2021.12

     View Summary

    The mammalian brain is highly vulnerable to oxygen deprivation, yet the mechanism underlying the brain’s sensitivity to hypoxia is incompletely understood. Hypoxia induces accumulation of hydrogen sulfide, a gas that inhibits mitochondrial respiration. Here, we show that, in mice, rats, and naturally hypoxia-tolerant ground squirrels, the sensitivity of the brain to hypoxia is inversely related to the levels of sulfide:quinone oxidoreductase (SQOR) and the capacity to catabolize sulfide. Silencing SQOR increased the sensitivity of the brain to hypoxia, whereas neuron-specific SQOR expression prevented hypoxia-induced sulfide accumulation, bioenergetic failure, and ischemic brain injury. Excluding SQOR from mitochondria increased sensitivity to hypoxia not only in the brain but also in heart and liver. Pharmacological scavenging of sulfide maintained mitochondrial respiration in hypoxic neurons and made mice resistant to hypoxia. These results illuminate the critical role of sulfide catabolism in energy homeostasis during hypoxia and identify a therapeutic target for ischemic brain injury.

  • Discovery of an F-actin-binding small molecule serving as a fluorescent probe and a scaffold for functional probes.

    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

    Science advances 7 ( 47 ) eabg8585 2021.11

  • Recent advances in detection, isolation, and imaging techniques for sulfane sulfur-containing biomolecules

    Echizen H., Sasaki E., Hanaoka K.

    Biomolecules (Biomolecules)  11 ( 11 )  2021.11

     View Summary

    Hydrogen sulfide and its oxidation products are involved in many biological processes, and sulfane sulfur compounds, which contain sulfur atoms bonded to other sulfur atom(s), as found in hydropersulfides (R-S-SH), polysulfides (R-S-Sn-S-R), hydrogen polysulfides (H2Sn), etc., have at-tracted increasing interest. To characterize their physiological and pathophysiological roles, selective detection techniques are required. Classically, sulfane sulfur compounds can be detected by cyanolysis, involving nucleophilic attack by cyanide ion to cleave the sulfur–sulfur bonds. The generated thiocyanate reacts with ferric ion, and the resulting ferric thiocyanate complex can be easily detected by absorption spectroscopy. Recent exploration of the properties of sulfane sulfur compounds as both nucleophiles and electrophiles has led to the development of various chemical techniques for detection, isolation, and bioimaging of sulfane sulfur compounds in biological samples. These include tag-switch techniques, LC-MS/MS, Raman spectroscopy, and fluorescent probes. Herein, we present an overview of the techniques available for specific detection of sulfane sulfur species in biological contexts.

  • A Sulfonyl Azide-Based Sulfide Scavenger Rescues Mice from Lethal Hydrogen Sulfide Intoxication

    Miyazaki Y., Marutani E., Ikeda T., Ni X., Hanaoka K., Xian M., Ichinose F.

    Toxicological Sciences (Toxicological Sciences)  183 ( 2 ) 393 - 403 2021.10

    ISSN  10966080

     View Summary

    Exposure to hydrogen sulfide (H2S) can cause neurotoxicity and cardiopulmonary arrest. Resuscitating victims of sulfide intoxication is extremely difficult, and survivors often exhibit persistent neurological deficits. However, no specific antidote is available for sulfide intoxication. The objective of this study was to examine whether administration of a sulfonyl azide-based sulfide-specific scavenger, SS20, would rescue mice in models of H2S intoxication: Ongoing exposure and post-cardiopulmonary arrest. In the ongoing exposure model, SS20 (1250 μmol/kg) or vehicle was administered to awake CD-1 mice intraperitoneally at 10 min after breathing 790 ppm of H2S followed by another 30 min of H2S inhalation. Effects of SS20 on survival were assessed. In the post-cardiopulmonary arrest model, cardiopulmonary arrest was induced by an intraperitoneal administration of sodium sulfide nonahydrate (125 mg/kg) in anesthetized mice. After 1 min of cardiopulmonary arrest, mice were resuscitated with intravenous administration of SS20 (250 μmol/kg) or vehicle. Effects of SS20 on survival, neurological outcomes, and plasma H2S levels were evaluated. Administration of SS20 during ongoing H2S inhalation improved 24-h survival (6/6 [100%] in SS20 vs 1/6 [17%] in vehicle; p =. 0043). Post-arrest administration of SS20 improved 7-day survival (4/10 [40%] in SS20 vs 0/10 [0%] in vehicle; p =. 0038) and neurological outcomes after resuscitation. SS20 decreased plasma H2S levels to pre-arrest baseline immediately after reperfusion and shortened the time to return of spontaneous circulation and respiration. These results suggest that SS20 is an effective antidote against lethal H2S intoxication, even when administered after cardiopulmonary arrest.

  • Matrix metalloprotease–14 is a target enzyme for detecting peritoneal metastasis in gastric cancer

    Ogawa S., Kubo H., Murayama Y., Kubota T., Yubakami M., Matsumoto T., Ohashi T., Okamoto K., Kuriki Y., Hanaoka K., Urano Y., Otsuji E.

    Photodiagnosis and Photodynamic Therapy (Photodiagnosis and Photodynamic Therapy)  35   102420 2021.09

    ISSN  15721000

     View Summary

    Background: Accurate diagnosis of peritoneal metastasis in gastric cancer (GC) is important to determine the appropriate treatment. This study aimed to examine whether matrix metalloprotease–14 (MMP–14) was a candidate enzyme in fluorescence imaging for the diagnosis of peritoneal metastasis in GC. Methods: GC and normal peritoneal (NP) tissues from 96 and 20 patients, respectively were evaluated for MMP–14 expression. Live cell imaging of GC cell lines (NUGC4, MKN45, MKN74, HGC-27, and Kato-III) was performed using the MMP–14-activatable fluorescence probe; BODIPY-MMP. Furthermore, the overall survival (OS) was calculated in all patients (n = 96). Results: MMP–14 expression was significantly higher in GC tissues (median: 3.57 ng/mg protein; range:0.64–24.4 ng/mg protein) than in NP tissues (median: 1.34 ng/mg protein; median: 0.53–3.09 ng/mg protein) (P < 0.01). Receiver operating characteristic curves showed that the area under the curve, sensitivity, and specificity were 0.907, 84.4%, and 90.0%, respectively. In live cell imaging using the BODIPY-MMP, fluorescence was observed in five GC cell lines. In the analysis of OS, the high expression of the MMP–14 group had a significantly poorer OS rate than the low expression of the MMP–14 group (P = 0.02). In the multivariate analyses, MMP-14 expression was an independent risk factor for OS (hazard ratio: 2.33; 95 % confidence interval: 1.05–5.45; P = 0.04). Conclusion: MMP–14 is a promising enzyme in intraoperative fluorescence imaging for peritoneal metastasis in GC, especially in patients with poor prognosis.

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Reviews, Commentaries, etc. 【 Display / hide

  • Recent advances in detection, isolation, and imaging techniques for sulfane sulfur-containing biomolecules

    Honami Echizen, Eita Sasaki, Kenjiro Hanaoka

    Biomolecules (MDPI)  11 ( 11 ) 1553 2021.10

    Introduction and explanation (scientific journal), Joint Work

  • Fluorescent labeling reagent

    Hanaoka K.

    Drug Delivery System (Drug Delivery System)  32 ( 5 ) 425 - 429 2017

    ISSN  09135006

  • Cover Picture: Unexpected Photo-instability of 2,6-Sulfonamide-Substituted BODIPYs and Its Application to Caged GABA (ChemBioChem 13/2016)

    Takeda A., Komatsu T., Nomura H., Naka M., Matsuki N., Ikegaya Y., Terai T., Ueno T., Hanaoka K., Nagano T., Urano Y.

    ChemBioChem (ChemBioChem)  17 ( 13 )  2016.07

    ISSN  14394227

  • Silicon-substituted xanthene dyes and their applications in bioimaging

    Kushida Y., Nagano T., Hanaoka K.

    Analyst (Analyst)  140 ( 3 ) 685 - 695 2015.02

    ISSN  00032654

     View Summary

    Fluorescence imaging is one of the most powerful techniques for visualizing temporal and spatial changes of biological phenomena in living cells, and many fluorescent probes have been developed. In particular, xanthene dyes such as fluorescein and rhodamines have favorable characteristics, such as high water solubility, high fluorescence quantum yield and high molar extinction coefficient, and they have been utilized as fluorescent cores for fluorescent probes working in the green to red wavelength region. Recently, silicon-substituted xanthene dyes such as 2,7-N,N,N′,N′-tetramethyl-9-dimethyl-10-hydro-9-silaanthracene (TMDHS), Si-rhodamines and TokyoMagentas, in which the O atom at the 10-position of xanthene is replaced with a Si atom, have been developed as novel far-red to near-infrared fluorescent cores that retain the key advantages of the parent structures. Fluorescent probes based on them have opened up new possibilities for imaging biological processes in living cells. This minireview covers recent progress in silicon-substituted xanthene dyes, including representative applications for in vivo tumor imaging, triple-color imaging of neuronal activity, and super-resolution microscopy.

Presentations 【 Display / hide

  • 活性硫黄分子種を検出する蛍光プローブの開発とその応用

    花岡 健二郎

    生理研研究会2021:生命を支える硫黄生物学の最前線 (東北大学加齢医学研究所) , 2021.07, Oral Presentation(general)

  • 新規蛍光団の創製を基盤とした蛍光プローブの開発

    花岡 健二郎

    第42回 光化学若手の会 (オンライン) , 2021.06, Oral Presentation(guest/special)

Research Projects of Competitive Funds, etc. 【 Display / hide

  • モダリティ別蛍光プローブ・イメージング法とがんモデルの選択及び最適化による薬物動態評価法の開発

    2021.11
    -
    2026.03

    国立研究開発法人日本医療研究開発機構(AMED), 創薬基盤推進研究事業, 安永 正浩, Commissioned research, Co-investigator

  • 超硫黄分子のマルチイメージングとその生合成制御のためのケミカルツール開発

    2021.09
    -
    2026.03

    科学研究費助成事業, 科学研究費補助金, 花岡 健二郎, 学術変革領域研究(A) 計画研究, Research grant, Principal Investigator

  • QM/MMに基づく分子動力学計算による新規蛍光プローブの分子設計

    2020.04
    -
    2023.03

    科学研究費助成事業, 科学研究費補助金, 八木 清, 基盤研究B(一般), Research grant, Co-investigator

  • Development of inhibiotrs for reactive sulfur species-producing enzymes by utilizing fluorescent probes and their biological analysis

    2020.04
    -
    2021.09

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 花岡 健二郎, Grant-in-Aid for Scientific Research on Innovative Areas, Research grant, Principal Investigator

Awards 【 Display / hide

  • 第3回 島津奨励賞

    2020, (公財) 島津科学技術振興財団

    Type of Award: Awards of Publisher, Newspaper Company and Foundation

  • ICBS Young Chemical Biologist Award

    2014, International Chemical Biology Society

    Type of Award: Awards of International Conference, Council and Symposium

  • 平成25年度 中谷賞 奨励賞

    2013, (公財) 中谷医工計測技術振興財団

    Type of Award: Awards of Publisher, Newspaper Company and Foundation

  • 第6回バイオ関連化学シンポジウム・講演賞

    2012, 日本化学会・生体機能関連化学部会

    Type of Award: Awards of National Conference, Council and Symposium

  • 平成23年度 文部科学大臣表彰顕彰若手科学者賞

    2011, 文部科学賞

    Type of Award: Other Awards

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Courses Taught 【 Display / hide

  • STUDY OF MAJOR FIELD (ANALYTICAL CHEMISTRY FOR DRUG DISCOVERY)

    2021

  • SEMINAR (ANALYTICAL CHEMISTRY FOR DRUG DISCOVERY)

    2021

  • RESEARCH FOR BACHELOR'S THESIS 1

    2021

  • PHYSICAL CHEMISTRY 2

    2021

  • PHARMACEUTICS LABORATORY COURSE

    2021

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Memberships in Academic Societies 【 Display / hide

  • 日本分子イメージング学会, 

    2007
    -
    Present
  • 日本ケミカルバイオロジー学会, 

    2007
    -
    Present
  • (公財)日本分析化学会, 

    2007
    -
    Present
  • (公財)日本薬学会, 

    2007
    -
    Present
  • (公財)日本化学会, 

    2007
    -
    Present

Committee Experiences 【 Display / hide

  • 2019
    -
    Present

    理事, 日本分子イメージング学会

  • 2017
    -
    Present

    世話人, 日本ケミカルバイオロジー学会