加部 泰明 (カベ ヤスアキ)

Kabe, Yasuaki

写真a

所属(所属キャンパス)

医学部 医化学教室 (信濃町)

職名

准教授

外部リンク

経歴 【 表示 / 非表示

  • 2004年04月
    -
    2006年03月

    東京工業大学, 生命理工学研究科, NEDOプロジェクト・研究員

  • 2007年04月
    -
    2009年03月

    東京工業大学, 生命理工学研究科, COE・特別研究助手

  • 2009年04月
    -
    2010年10月

    慶應義塾大学, 医学部・GCOE, 特別研究講師

  • 2010年11月
    -
    継続中

    慶應義塾大学, 医学部・医化学教室, 専任講師

学歴 【 表示 / 非表示

  • 1993年04月
    -
    1997年03月

    東北大学, 薬学部薬学科

    大学, 卒業, 修士

  • 1997年04月
    -
    1999年03月

    東北大学, 薬学研究科

    大学院, 修了, 修士

  • 1999年04月
    -
    2003年03月

    東京工業大学, 生命理工学研究科

    大学院, 修了, 博士後期

学位 【 表示 / 非表示

  • 博士(工学), 東京工業大学, 課程, 2003年03月

    核内レセプターAd4BP/SF-1およびVDR の活性化機構の解析

免許・資格 【 表示 / 非表示

  • 国家薬剤師免許, 1997年

 

研究分野 【 表示 / 非表示

  • 分子生物学

  • 医化学一般

研究キーワード 【 表示 / 非表示

  • ケミカルバイオロジー

  • ヘム

  • 機能性食品

 

論文 【 表示 / 非表示

  • Application of high-performance magnetic nanobeads to biological sensing devices

    Kabe Y., Sakamoto S., Hatakeyama M., Yamaguchi Y., Suematsu M., Itonaga M., Handa H.

    Analytical and Bioanalytical Chemistry (Analytical and Bioanalytical Chemistry)  411 ( 9 ) 1825 - 1837 2019年03月

    ISSN  16182642

     概要を見る

    © 2019, The Author(s). Nanomaterials have extensive applications in the life sciences and in clinical diagnosis. We have developed magnetic nanoparticles with high dispersibility and extremely low nonspecific binding to biomolecules and have demonstrated their application in chemical biology (e.g., for the screening of drug receptor proteins). Recently, the excellent properties of nanobeads have made possible the development of novel rapid immunoassay systems and high-precision technologies for exosome detection. For immunoassays, we developed a technology to encapsulate a fluorescent substance in magnetic nanobeads. The fluorescent nanobeads allow the rapid detection of a specific antigen in solution or in tissue specimens. Exosomes, which are released into the blood, are expected to become markers for several diseases, including cancer, but techniques for measuring the absolute quantity of exosomes in biological fluids are lacking. By integrating magnetic nanobead technology with an optical disc system, we developed a novel method for precisely quantifying exosomes in human serum with high sensitivity and high linearity without requiring enrichment procedures. This review focuses on the properties of our magnetic nanobeads, the development of novel biosensors using these nanobeads, and their broad practical applications. [Figure not available: see fulltext.].

  • Gold-nanofève surface-enhanced Raman spectroscopy visualizes hypotaurine as a robust anti-oxidant consumed in cancer survival

    Shiota M., Naya M., Yamamoto T., Hishiki T., Tani T., Takahashi H., Kubo A., Koike D., Itoh M., Ohmura M., Kabe Y., Sugiura Y., Hiraoka N., Morikawa T., Takubo K., Suina K., Nagashima H., Sampetrean O., Nagano O., Saya H., Yamazoe S., Watanabe H., Suematsu M.

    Nature Communications (Nature Communications)  9 ( 1 )  2018年12月

     概要を見る

    © 2018 The Author(s). Gold deposition with diagonal angle towards boehmite-based nanostructure creates random arrays of horse-bean-shaped nanostructures named gold-nanofève (GNF). GNF generates many electromagnetic hotspots as surface-enhanced Raman spectroscopy (SERS) excitation sources, and enables large-area visualization of molecular vibration fingerprints of metabolites in human cancer xenografts in livers of immunodeficient mice with sufficient sensitivity and uniformity. Differential screening of GNF-SERS signals in tumours and those in parenchyma demarcated tumour boundaries in liver tissues. Furthermore, GNF-SERS combined with quantum chemical calculation identified cysteine-derived glutathione and hypotaurine (HT) as tumour-dominant and parenchyma-dominant metabolites, respectively. CD44 knockdown in cancer diminished glutathione, but not HT in tumours. Mechanisms whereby tumours sustained HT under CD44-knockdown conditions include upregulation of PHGDH, PSAT1 and PSPH that drove glycolysis-dependent activation of serine/glycine-cleavage systems to provide one-methyl group for HT synthesis. HT was rapidly converted into taurine in cancer cells, suggesting that HT is a robust anti-oxidant for their survival under glutathione-suppressed conditions.

  • Baicalein Targets GTPase-Mediated Autophagy to Eliminate Liver Tumor–Initiating Stem Cell–Like Cells Resistant to mTORC1 Inhibition

    Wu R., Murali R., Kabe Y., French S., Chiang Y., Liu S., Sher L., Wang C., Louie S., Tsukamoto H.

    Hepatology (Hepatology)  68 ( 5 ) 1726 - 1740 2018年11月

    ISSN  02709139

     概要を見る

    © 2018 by the American Association for the Study of Liver Diseases. Drug resistance is a major problem in the treatment of liver cancer. Mammalian Target of Rapamycin 1 (mTORC1) inhibitors have been tested for the treatment of liver cancer based on hyperactive mTOR in this malignancy. However, their clinical trials showed poor outcome, most likely due to their ability to upregulate CD133 and promote chemoresistance. The CD133 + tumor–initiating stem cell–like cells (TICs) isolated from mouse and human liver tumors are chemoresistant, and identification of an approach to abrogate this resistance is desired. In search of a compound that rescinds resistance of TICs to mTORC1 inhibition and improves chemotherapy, we identified baicalein (BC), which selectively chemosensitizes TICs and the human hepatocellular carcinoma (HCC) cell line Huh7 cells but not mouse and human primary hepatocytes. Nanobead pull-down and mass-spectrometric analysis, biochemical binding assay, and three-dimensional computational modeling studies reveal BC's ability to competitively inhibit guanosine triphosphate binding of SAR1B guanosine triphosphatase, which is essential for autophagy. Indeed, BC suppresses autophagy induced by an mTORC1 inhibitor and synergizes cell death caused by mTORC1 inhibition in TIC and Huh7 spheroid formation and in the patient-derived xenograft model of HCC. The BC-induced chemosensitization is rescued by SAR1B expression and phenocopied by SAR1B knockdown in cancer cells treated with a mTORC1 inhibitor. Conclusion: These results identify SAR1B as a target in liver TICs and HCC cells resistant to mTORC1 inhibition.

  • Development of a highly sensitive device for counting the number of disease-specific exosomes in human sera

    Kabe Y., Suematsu M., Sakamoto S., Hirai M., Koike I., Hishiki T., Matsuda A., Hasegawa Y., Tsujita K., Ono M., Minegishi N., Hozawa A., Murakami Y., Kubo M., Itonaga M., Handa H.

    Clinical Chemistry (Clinical Chemistry)  64 ( 10 ) 1463 - 1473 2018年10月

    ISSN  00099147

     概要を見る

    © 2018 American Association for Clinical Chemistry BACKGROUND: Although circulating exosomes in blood play crucial roles in cancer development and progression, difficulties in quantifying exosomes hamper their application for reliable clinical testing. By combining the properties of nanobeads with optical disc technology, we have developed a novel device named the ExoCounter to determine the exact number of exosomes in the sera of patients with various types of cancer. METHOD: In this system, individual exosomes were captured in the groove of an optical disc coated with antibodies against exosome surface antigens. The captured exosomes were labeled with antibody-conjugated magnetic nanobeads, and the number of the labeled exosomes was counted with an optical disc drive. RESULTS: We showed that the ExoCounter could detect specific exosomes derived from cells or human serum without any enrichment procedures. The detection sensitivity and linearity with this system were higher than those with conventional detection methods such as ELISA or flow cytometry. In addition to the ubiquitous exosome markers CD9 and CD63, the cancer-related antigens CD147, carcinoembryonic antigen, and human epidermal growth factor receptor 2 (HER2) were also used to quantify cancer cell line-derived exosomes. Furthermore, analyses of a cross-sectional cohort of sera samples revealed that HER2-positive exosomes were significantly increased in patients with breast cancer or ovarian cancer compared with healthy individuals and those with noncancer diseases. CONCLUSIONS: The ExoCounter system exhibits high performance in the direct detection of exosomes in cell culture and human sera. This method may enable reliable analysis of liquid biopsies.

  • Function and structural regulation of the carbon monoxide (CO)-responsive membrane protein PGRMC1

    Kabe Y., Handa H., Suematsu M.

    Journal of Clinical Biochemistry and Nutrition (Journal of Clinical Biochemistry and Nutrition)  63 ( 1 ) 12 - 17 2018年07月

    ISSN  09120009

     概要を見る

    © 2018 JCBN. Progesterone receptor membrance associated component 1 is a multifunctional heme-binding protein that plays a role in several biological processes such as tumor progression, metabolic regulation, and viability control of nerve cells. Notably, progesterone receptor membrane associated component 1 is highly expressed in various types of cancer cells, and facilitates cancer proliferation and chemoresistance. Recently, progesterone receptor membrane associated component 1 structure has been explored by X-ray crystallographic analysis. Interestingly, whereas apoprogesterone receptor membrane associated component 1 exists as a monomer, the heme-bound progesterone receptor membrane associated component 1 converts into a stable dimer by forming a unique heme-heme stacking structure, leading to activation of epidermal growth factor receptor signaling and chemoresistance in cancer cells. Furthermore, the gas mediator carbon monoxide inhibits progesterone receptor membrane associated component 1-mediated activation in cancer cells by dissociating the heme-stacking dimer of progesterone receptor membrane associated component 1. The dynamic structural regulation of progesterone receptor membrane associated component 1 will provide new insights for understanding the mechanisms underlying its various functions.

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KOARA(リポジトリ)収録論文等 【 表示 / 非表示

競争的資金等の研究課題 【 表示 / 非表示

  • 膜受容体PGRMC1の構造的知見を基盤とした生理機能の解明と制御化合物の解析

    2018年04月
    -
    2021年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 加部 泰明, 基盤研究(C), 補助金,  代表

  • 膜結合性ヘムタンパク質PGRMC1の構造的制御による生理機能の解明

    2015年04月
    -
    2018年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 加部 泰明, 基盤研究(C), 補助金,  代表

知的財産権等 【 表示 / 非表示

  • インフラマソーム活性化制御物質のスクリーニング方法

    特願: 特願 2014-146255  2014年11月 

    特許, 共同, 国内出願

  • 一酸化炭素(CO)による脂肪酸、コレステロールの取り込み阻害

    特願: 特願 2011-263015   

    特許, 共同, 国内出願

  • GAPDHの酵素活性阻害剤

    特願: 特願2010-192513   

    特許, 単独, 国内出願

 

担当授業科目 【 表示 / 非表示

  • 医化学

    2019年度

担当経験のある授業科目 【 表示 / 非表示

  • 医化学講義

    慶應義塾, 2015年度, 通年, 専門科目, 講義, 兼担, 120人

    アミノ酸代謝、栄養元素、ケミカルバイオロジー

  • 医化学実習

    慶應義塾, 2015年度, 秋学期, 実習・実験, 兼担, 120人

    タンパク質精製、代謝制御

  • 修士分子生物学講義

    慶應義塾, 2015年度, 春学期, 専門科目, 講義, 兼担, 15人

    ケミカルバイオロジー