関 智宏 (セキ トモヒロ)

Seki Tomohiro

写真a

職名

助教

生年

1987年

研究室住所

〒350-0295 埼玉県坂戸市けやき台1-1、城西大学 21号館 423室

研究分野・キーワード

ドラッグデリバリーシステム、製剤学、超分子化学

メールアドレス

メールアドレス

研究室電話

049-271-8107

研究室FAX

049-271-8107

出身大学 【 表示 / 非表示

  • 2006年04月
    -
    2012年03月

    城西大学   薬学部   薬学科   卒業

出身大学院 【 表示 / 非表示

  • 2012年04月
    -
    2016年03月

    城西大学  薬学研究科  薬学専攻  博士課程  修了

取得学位 【 表示 / 非表示

  • 城西大学 -  博士(薬学)

学内職務経歴 【 表示 / 非表示

  • 2019年04月
    -
    継続中

    城西大学   薬学部   薬学科   助教  

学外略歴 【 表示 / 非表示

  • 2016年07月
    -
    2018年01月

      米国立衛生研究所   研究員

  • 2018年02月
    -
    2019年03月

      米国立衛生研究所   日本学術振興会 海外特別研究員(NIH)

所属学会・委員会 【 表示 / 非表示

  • 2012年03月
    -
    継続中
     

    日本薬剤学会

  • 2011年03月
    -
    継続中
     

    日本薬学会

  • 2011年03月
    -
    2016年07月
     

    日本DDS学会

  • 2011年03月
    -
    2016年07月
     

    日本シクロデキストリン学会

専門分野(科研費分類) 【 表示 / 非表示

  • 物理系薬学

取得資格 【 表示 / 非表示

  • 薬剤師

 

研究経歴 【 表示 / 非表示

  • CD44陽性がん標的指向性を有するプロドラッグ型グルタチオン応答薬物放出システム

    (選択しない)  

    研究期間: 2019年04月  -  継続中

  • 動的核偏極MRIを用いた非侵襲的in vivo腫瘍代謝イメージング

    (選択しない)  

    研究期間: 2016年07月  -  2019年03月

  • 糖応答性インスリン放出システムに関する

    (選択しない)  

    研究期間: 2010年04月  -  2016年07月

学位論文 【 表示 / 非表示

  • 糖応答性分子ネックレスを用いたインスリンコントロールドリリースシステムに関する研究

    関 智宏

      2016年03月

    学位論文(博士)   単著

論文 【 表示 / 非表示

  • Metabolic Reprogramming Associated with Aggressiveness Occurs in the G-CIMP-High Molecular Subtypes of IDH1mut Lower Grade Gliomas

    Ruiz-Rodado Victor, Tathiane M Malta, Tomohiro Seki, Adrian Lita, Tyrone Dowdy, Orieta Celiku, Alejandra Cavazos-Saldana, Aiguo Li, Yang Liu, Sue Han, Wei Zhang, Hua Song, Dionne Davis, Sunmin Lee, Jane B Trepel, Thais S Sabedot, Jeeva Munasinghe, Chunzhang Yang, Christel Herold-Mende, Mark R Gilbert, Murali Krishna Cherukuri, Houtan Noushmehr, Mioara Larion

    Neuro-Oncology     2019年10月  [査読有り]

    共著

    Background
    Early detection of increased aggressiveness of brain tumors is a major challenge in the field of neuro-oncology because of the inability of traditional imaging to uncover it. IDH-mutant gliomas represent an ideal model system to study the molecular mechanisms associated with tumorigenicity because they appear indolent and non-glycolytic initially, but eventually a subset progresses towards secondary glioblastoma with a Warburg-like phenotype. The mechanisms and molecular features associated with this transformation are poorly understood.
    Methods
    We employed model systems for IDH1 mutant gliomas with different growth and proliferation rates in vivo and in vitro. We described the metabolome, transcriptome and epigenome of these models in order to understand the link between their metabolism and the tumor biology. To verify whether this metabolic reprogramming occurs in the clinic we analyzed TCGA data.
    Results
    We reveal that the aggressive glioma models have lost DNA methylation in the promoters of glycolytic enzymes, especially LDHA, and have increased mRNA and metabolite levels compared to the indolent model. We find that the acquisition of the high glycolytic phenotype occurs at the G-CIMP-high molecular subtype in patients and is associated with the worst outcome.
    Conclusion
    We propose very early monitoring of lactate levels as a biomarker of metabolic reprogramming and tumor aggressiveness.

    DOI

  • Dynamic Imaging of Glucose and Lactate Metabolism by 13C-MRS without Hyperpolarization

    Brender JR, Kishimoto S, Merkle H, Reed G, Hurd RE, Chen AP, Ardenkjaer-Larsen JH, Munasinghe J, Saito K, Seki T, Oshima N, Yamamoto K, Choyke PL, Mitchell J, Krishna MC

    Scientific Reorts   9   3410   2019年  [査読有り]

    共著

    Metabolic reprogramming is one of the defining features of cancer and abnormal metabolism is associated with many other pathologies. Molecular imaging techniques capable of detecting such changes have become essential for cancer diagnosis, treatment planning, and surveillance. In particular, 18F-FDG (fluorodeoxyglucose) PET has emerged as an essential imaging modality for cancer because of its unique ability to detect a disturbed molecular pathway through measurements of glucose uptake. However, FDG-PET has limitations that restrict its usefulness in certain situations and the information gained is limited to glucose uptake only.13C magnetic resonance spectroscopy theoretically has certain advantages over FDG-PET, but its inherent low sensitivity has restricted its use mostly to single voxel measurements unless dissolution dynamic nuclear polarization (dDNP) is used to increase the signal, which brings additional complications for clinical use. We show here a new method of imaging glucose metabolism in vivo by MRI chemical shift imaging (CSI) experiments that relies on a simple, but robust and efficient, post-processing procedure by the higher dimensional analog of singular value decomposition, tensor decomposition. Using this procedure, we achieve an order of magnitude increase in signal to noise in both dDNP and non-hyperpolarized non-localized experiments without sacrificing accuracy. In CSI experiments an approximately 30-fold increase was observed, enough that the glucose to lactate conversion indicative of the Warburg effect can be imaged without hyper-polarization with a time resolution of 12s and an overall spatial resolution that compares favorably to 18F-FDG PET.

    DOI

  • Sugar-responsive smart materials based on phenylboronic acid and cyclodextrin

    Yuya Egawa, Tomohiro Seki, Ryotaro Miki, Toshinobu Seki

    Journal of Inclusion Phenomena and Macrocyclic Chemistry   94 ( 1-2 ) 1 - 10   2019年  [招待有り]

    共著

    This review focuses on sugar-responsive materials based on phenylboronic acid (PBA) as a sugar-sensing motif and cyclodextrins (CyDs) as a basic skeleton of smart materials. PBA modified α-CyD (PBA-α-CyD) forms a supramolecular polymer through intermolecular interactions between PBA part and CyD cavity. Similarly, PBA-β-CyD forms a head-to-head dimer. Meanwhile, combining PBA-γ-CyD and polyethylene glycol (PEG) produces a molecular necklace. Additionally, combining PBA-modified PEG and native α-CyD or γ-CyD results in another type of molecular necklace. These supramolecular structures are obtained as powders, and their solubility increases in the presence of sugar. Besides the powder type, a unique gel is formed through crosslinking polyvinyl alcohol with PBA-triazole-γ-CyD (PBA-Tri-γ-CyD). This gel can contain model drug, and it shows sugar-responsive drug release. The sugar response of all of these smart materials can be explained by the concept of equilibrium. The smart materials are constructed with CyD-guest interactions. The CyD-guest equilibrium moves by a reaction between sugar and PBA moiety attached to the smart material. In these smart materials, sugar induces a dissociation in the CyD-guest interaction, and this dissociation results in sugar-induced disintegration of CyD-guest supramolecular structures.

  • Cell Adhesive Character of Phenylboronic Acid-Modified Insulin and Its Potential as Long-Acting Insulin

    Yui Ohno, Momoko Kawakami, Tomohiro Seki, Ryotaro Miki, Toshinobu Seki and Yuya Egawa

    Pharmaceuticals   12 ( 3 ) 121   2019年  [査読有り]

    共著

    Phenylboronic acid (PBA) derivatives have attracted substantial attention owing to their unique character of forming dynamic covalent bonds with polyol compounds. Recent studies have shown interactions between PBA and sugar chains on the cell surface; they have interesting applications for sensors and drug delivery systems. In this study, we prepared phenylboronic acid-modified insulin (PBA-Ins) to evaluate its glucose-lowering activity and cell adhesiveness. In the case of intravenous injection, PBA-Ins showed longer glucose-lowering activity than native insulin. We hypothesized that this prolonged effect was the result of the interaction between the PBA moiety and sugar chains on the cell surface. Red blood cells (RBCs) were used as a cell model, and we confirmed PBA-Ins’s affinity for RBCs, which induced RBC agglutination. Interestingly, using an alternative PBA-Ins administration route markedly changed its glucose-lowering activity. Unlike the intravenous injection of PBA-Ins, the subcutaneous injection showed a small effect on glucose level, which indicated that a small amount of PBA-Ins was absorbed into the bloodstream. This suggested the importance of investigating the interaction between the PBA moiety and many types of cells, such as adipocytes, in subcutaneous tissues.

    DOI

  • Investigation of factors that cause insulin precipitation and/or amyloid formation in insulin formulations

    Yui Ohno, Tomohiro Seki, Yu Kojima, Ryotaro Miki, Yuya Egawa, Osamu Hosoya, Keizo Kasono, Toshinobu Seki

    Journal of Pharmaceutical Health Care and Sciences ( Springer Nature )  in press   2019年  [査読有り]

    共著

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学術関係受賞 【 表示 / 非表示

  • JSPS Fellowship for Japanese Biomedical and Behavioral Researchers Fellowship at NIH Award

    2018年08月   Japan Society for the Promotion of Science (JSPS)  

    受賞者:  Tomohiro Seki

  • Excellent Poster Presentation Award GOLD Prize

    2014年11月   第20回創剤フォーラム若手研究会 (日本薬剤学会)  

    受賞者:  関 智宏

  • ポスター賞

    2014年09月   第31回シクロデキストリンシンポジウム (日本シクロデキストリン学会)  

    受賞者:  関 智宏

  • 若手研究奨励賞

    2014年07月   物理系薬学部会 (フィジカルファーマフォーラム2014)  

    受賞者:  関 智宏

  • Most Impressive Debater賞

    2014年05月   日本薬剤学会第29年会  

    受賞者:  関 智宏

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