慶應義塾研究者情報データベース

経歴 【 表示 ／ 非表示 】

経歴 【 表示 ／ 非表示 】

• 1998年05月

  -

  1999年03月

  東北大学, 薬学部, 助手

• 1999年04月

  -

  2007年03月

  東北大学, 大学院薬学研究科, 助手

• 2007年04月

  -

  2009年03月

  東北大学, 大学院薬学研究科, 助教

• 2009年04月

  -

  2021年03月

  東北大学, 大学院薬学研究科, 准教授

• 2021年04月

  -

  継続中

  慶應義塾大学, 薬学部, 教授

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• ライフサイエンス / 環境、天然医薬資源学 （天然物化学）

著書 【 表示 ／ 非表示 】

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• 細胞性粘菌：研究の新展開〜モデル生物，創薬資源，バイオ〜

  菊地晴久, 久保原禅, アイピーシー出版, 2012年

  担当範囲: 第１０章 創薬資源としての細胞性粘菌

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• Pharmacological Evidence That Dictyostelium Differentiation-Inducing Factor 1 Promotes Glucose Uptake Partly via an Increase in Intracellular cAMP Content in Mouse 3T3-L1 Cells

  Kubohara Y., Fukunaga Y., Kikuchi H., Kuwayama H.

  Molecules （Molecules）  28 （ 23 ）  2023年12月

  　概要を見る

  Differentiation-inducing factor 1 (DIF-1) isolated from the cellular slime mold Dictyostelium discoideum can inhibit mammalian calmodulin-dependent cAMP/cGMP phosphodiesterase (PDE1) in vitro. DIF-1 also promotes glucose uptake, at least in part, via a mitochondria- and AMPK-dependent pathway in mouse 3T3-L1 fibroblast cells, but the mechanism underlying this effect has not been fully elucidated. In this study, we investigated the effects of DIF-1 on intracellular cAMP and cGMP levels, as well as the effects that DIF-1 and several compounds that increase cAMP and cGMP levels have on glucose uptake in confluent 3T3-L1 cells. DIF-1 at 20 μM (a concentration that promotes glucose uptake) increased the level of intracellular cAMP by about 20% but did not affect the level of intracellular cGMP. Neither the PDE1 inhibitor 8-methoxymethyl-3-isobutyl-1-methylxanthine at 10–200 μM nor the broad-range PDE inhibitor 3-isobutyl-1-methylxanthine at 40–400 μM had any marked effects on glucose uptake. The membrane-permeable cAMP analog 8-bromo-cAMP at 200–1000 μM significantly promoted glucose uptake (by 20–25%), whereas the membrane-permeable cGMP analog 8-bromo-cGMP at 3–100 μM did not affect glucose uptake. The adenylate cyclase activator forskolin at 1–10 μM promoted glucose uptake by 20–30%. Thus, DIF-1 may promote glucose uptake by 3T3-L1 cells, at least in part, via an increase in intracellular cAMP level.

  • Access to Document (DOI)

• Derivatives of Differentiation-Inducing Factor 1 Differentially Control Chemotaxis and Stalk Cell Differentiation in Dictyostelium discoideum

  Hidekazu Kuwayama, Haruhisa Kikuchi, Yuzuru Kubohara

  Biology （Biology）  12 （ 6 ） 873 - 873 2023年06月

  査読有り

  　概要を見る

  Differentiation-inducing factors 1 and 2 (DIF-1 and DIF-2) are small lipophilic signal molecules that induce stalk cell differentiation but differentially modulate chemotaxis toward cAMP in the cellular slime mold Dictyostelium discoideum; DIF-1 suppresses chemotactic cell movement in shallow cAMP gradients, whereas DIF-2 promotes it. The receptor(s) for DIF-1 and DIF-2 have not yet been identified. We examined the effects of nine derivatives of DIF-1 on chemotactic cell movement toward cAMP and compared their chemotaxis-modulating activity and stalk cell differentiation–inducing activity in wild-type and mutant strains. The DIF derivatives differentially affected chemotaxis and stalk cell differentiation; for example, TM-DIF-1 suppressed chemotaxis and showed poor stalk-inducing activity, DIF-1(3M) suppressed chemotaxis and showed strong stalk-inducing activity, and TH-DIF-1 promoted chemotaxis. These results suggest that DIF-1 and DIF-2 have at least three receptors: one for stalk cell induction and two for chemotaxis modulation. In addition, our results show that the DIF derivatives can be used to analyze the DIF-signaling pathways in D. discoideum.

  • Access to Document (DOI)

• <i>Dictyostelium</i> Differentiation-inducing Factor Derivatives Reduce the Glycosylation of PD-L1 in MDA-MB-231 Human Breast Cancer Cells

  AIRI HIRAYAMA, HIROTAKA ISHIGAKI, KATSUNORI TAKAHASHI, YUSUKE MIURA, HARUHISA KIKUCHI, YUZURU KUBOHARA

  Juntendo Medical Journal （The Jutendo Medical Journal）  2023年

  ISSN  2187-9737

  • Access to Document (DOI)

• Elucidation of the inhibitory effect of (+)-hopeaphenol on polyinosinic–polycytidylic acid-induced innate immunity activation in human cerebral microvascular endothelial cells

  Xu L., Yu Z., Uekusa Y., Kawaguchi S., Kikuchi H., Daitoku K., Minakawa M., Motomura S., Furukawa K.I., Oshima Y., Seya K., Imaizumi T.

  Journal of Pharmacological Sciences （Journal of Pharmacological Sciences）  149 （ 3 ） 147 - 157 2022年07月

  ISSN  13478613

  　概要を見る

  Drug development for regulating the innate immune system is important for the prevention and treatment of autoinflammatory and autoimmune diseases. In this context, we investigated the effect of resveratrol derivatives on the inflammatory reactions in the brain. Resveratrol, which can be found in Vitis plants in the form of oligomers, exhibits neuroprotective effects; however, its regulatory effects on innate immunity are still unclear. We examined the effects of (+)-hopeaphenol, a resveratrol tetramer, and its derivatives on the polyinosinic–polycytidylic acid (poly IC)-induced production of interferon (IFN)-β and C-X-C motif chemokine 10 (CXCL10) in the cultured human cerebral microvascular endothelial cell line hCMEC/D3. (+)-Hopeaphenol (1–10 μM) inhibited the poly IC-induced production of not only CXCL10 but also retinoic acid-inducible gene-I in a dose-dependent manner and significantly reduced the poly IC-induced IFN-β gene expression and protein release from hCMEC/D3 cells by inhibiting the phosphorylation of p65 but not that of the interferon regulatory transcription factor IRF3. A docking study indicated a high affinity of (+)-hopeaphenol for p65. These results suggest that (+)-hopeaphenol can regulate the innate immune system by inhibiting the poly IC/IFN-β/CXCL10 signaling axis via suppression of the phosphorylation of the transcription factor NF-ĸB.

  • Access to Document (DOI)

• Glycidyl Silanes Enable Regioselective Hydrosilylation of In-ternal Propargyl Alcohols and Direct Transformation into Activated Silanes for Further Chemical Transformation

  Akihiro Sugawara, Soya Koremura, Yusuke Sasano, Haruhisa Kikuchi

  ChemRxiv （American Chemical Society (ACS)）  2022年04月

  最終著者

  　概要を見る

  Herein, we develop glycidyl silanes to facilitate highly regioselective hydrosilylation of internal propargyl alcohols, the products of which can in turn be converted to synthetically useful fluorosilanes for further chemical transfor-mations under mild conditions. Structure–selectivity studies and density functional theory calculations are consistent with high regioselectivity arising from a critical intermolecular hydrogen bond between the glycidyl and propargylic hydroxy groups. A broad substrate scope illustrates the generality of this reaction to form beta-E silylalkenes. Treatment of the beta-E silylalkenes with a fluoride salt induces simultaneous removal of the glycidyl group and activation of the silane under mild conditions. The fluorosilane products can be converted into vinyl arene and ketone derivatives via Hiyama coupling and Tamao–Fleming oxidation reactions, respectively. The discovery that glycidyl silane improves hydrosilylation regioselectivity and is compatible with expedient silylalkene derivatization may prove applicable to a variety of similar alkyne hydrofunctionalization reactions.

  • Access to Document (DOI)

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KOARA（リポジトリ）収録論文等 【 表示 ／ 非表示 】

KOARA（リポジトリ）収録論文等 【 表示 ／ 非表示 】

• 未利用原生生物の創薬資源化に関する研究

  菊地, 晴久

  学事振興資金研究成果実績報告書 （慶應義塾大学）  2022年

• 非生物元素が導入された天然化合物類縁体ライブラリーの創出

  菊地, 晴久

  福澤諭吉記念慶應義塾学事振興基金事業報告集 （福澤基金運営委員会）  2022年

総説・解説等 【 表示 ／ 非表示 】

総説・解説等 【 表示 ／ 非表示 】

• New Development of Disaster-Related and Tropical Infectious Diseases Control

  Gaowa Bai, Toshiro Niki, Haruhisa Kikuchi, Ayako Sumi, Nobuyuki Kobayashi, Takahiro Haruyama, Jing Zhang, Haorile Chagan-Yasutan, Toshio Hattori

  Reports — Medical Cases, Images, and Videos （MDPI AG）  3 （ 1 ） 5 - 5 2020年03月

  その他, 共著

  　概要を見る

  As described in Japanese essay (Hojoki), written around 1200, various disasters such as big fires, earthquakes, and famines have occurred in Japan. Asian countries have been suffering from the disasters; furthermore, natural disasters are increasing due to global warming. Because tropical-infectious diseases are often disaster-related infectious diseases (DRIDs), the strategies against the former kind of disease could be applicable to DRIDs. Meteorological analysis of the occurrence of DRIDs using a method of time series analysis is important. In situations of disasters, it is desirable if you can identify the pathogen and identify disease severity simultaneously. A dipstick DNA chromatography assay termed as Single-Tag Hybridization—Printed Array Strip (STH—PAS) system was developed based on the DNA sequences of various mosquito-borne diseases. The plasma levels of matricellular proteins including galectin-9 (Gal-9) and osteopontin (OPN) were found to reflect the disease severities in the dengue virus and other DIRDs. Because both proteins have been reported to be immune-check molecules, their inhibition might enhance the immune system against pathogens. We found that brefelamide derivatives could inhibit OPN and other inflammatory molecules synthesis. Very recently, different derivatives were found to inhibit PD-L1 transcription. Applications of these agents should be considered as multi-step strategies against DRIDs.

  • Access to Document (DOI)

• 多様性拡大抽出物を利用した天然化合物様ライブラリーの創出

  菊地晴久, 大島吉輝

  MedChem News 24 （ 2 ） 45 - 51 2014年

  記事・総説・解説・論説等（商業誌、新聞、ウェブメディア）, 共著

• 未利用微生物・細胞性粘菌から得られた新規生物活性物質（総説）

  菊地晴久

  薬学雑誌 （PHARMACEUTICAL SOC JAPAN）  127 （ 9 ） 1431 - 1439 2007年

  書評論文，書評，文献紹介等, 単著,  ISSN  0031-6903

  　概要を見る

  Cellular slime molds are thought to be excellent model organisms for the study of cell and developmental biology because of their simple pattern of development. However, there have been few reports on secondary metabolites of them. We have focused on the utility of cellular slime molds as novel resources for natural product chemistry, and have studied the diversity of secondary metabolites produced by them as well as their physiological and pharmacological activities. We have recently isolated many novel compounds from the fruiting bodies of various species of Dictyostelium cellular slime molds. Total syntheses and biological evaluation of these compounds have been carried out. It was shown that dictyopyrones and dictyomedins may regulate Dictyostelium development. Amino sugar derivatives such as furanodictines and dictyoglucosamines induced neuronal differentiation of rat PC-12 cells. In addition, brefelarnide inhibited the cellular proliferation of 1321N1 human astrocytorna cells. These results show that cellular slime molds are promising sources in natural product chemistry.

  • Access to Document (DOI)

• 細胞性粘菌の生活環を制御する物質−単細胞から多細胞への移行をコントロールするα-ピロノイド

  大島吉輝, 菊地晴久, 前田靖男

  化学と生物 40 （ 2 ） 76 - 77 2002年

  記事・総説・解説・論説等（商業誌、新聞、ウェブメディア）, 共著,  ISSN  0453-073X

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• Development of Natural Product-Like Compound Library Based on Diversity-Enhanced Extracts

  KIKUCHI Haruhisa

  The 5th Japan-Taiwan Joint Symposium for Pharmaceutical Sciences, 

  2019年08月

  , 

  シンポジウム・ワークショップ パネル（指名）

• 創薬シーズを指向した天然物を越える構造多様化合物群の創出

  菊地 晴久

  BINDS: ケミカルシーズ・リード探索ユニットジョイントシンポジウム 2019 IN 仙台, 

  2019年05月

  , 

  シンポジウム・ワークショップ パネル（指名）

• Development of Natural Product-Like Compound Library Based on Diversity-Enhanced Extracts

  KIKUCHI Haruhisa

  The 2nd International Symposium on Chemical Communication, 

  2018年05月

  , 

  口頭発表（招待・特別）

• Diversity enhanced extract: a new approach for increasing chemical diversity of natural product-like compounds

  KIKUCHI Haruhisa

  Tohoku University’s Chemistry Summer School, 

  2016年08月

  , 

  口頭発表（基調）

• 多様性拡大抽出物を活用した天然化合物類縁体ライブラリーの創出

  菊地晴久

  日本薬学会第136年会 シンポジウム MONOTORIの新戦略, 

  2016年03月

  , 

  シンポジウム・ワークショップ パネル（指名）

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競争的研究費の研究課題 【 表示 ／ 非表示 】

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• 天然化合物を越える多様性を有した生物活性指向型化合物ライブラリーの構築

  2019年04月

  -

  2022年03月

  文部科学省・日本学術振興会, 科学研究費助成事業, 菊地 晴久, 基盤研究(B), 補助金,  研究代表者

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• 不飽和複素5員環含有化合物を含有する肺高血圧症の予防又は治療剤

  出願日： JP2017025822  2017年07月 

  公開日： WO2018-012634  2018年01月 

  特許権

• アミド誘導体

  出願日： JP2015055873  2015年02月 

  公開日： WO2015-129860  2015年09月 

  特許権

• 抗菌剤

  出願日： 特願2014-160596  2014年08月 

  公開日： 特開2016-037456  2016年03月 

  特許権

• ジクチオピロン誘導体又はジヒドロジクチオピロン誘導体を有効成分とするオステオポンチン産生阻害剤

  出願日： JP2013006943  2013年11月 

  公開日： WO2014-136161  2014年09月 

  特許権

• ジクチオピロン誘導体又はジヒドロジクチオピロン誘導体を有効成分とするオステオポンチン産生阻害剤

  出願日： 特願2014-552995  2013年11月 

  発行日： 特許第5716140号  2015年03月

  特許権

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受賞 【 表示 ／ 非表示 】

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• 日本生薬学会学術貢献賞

  2022年, 日本生薬学会

• 第９回インテリジェント・コスモス奨励賞

  2010年

• 第46回天然有機化合物討論会奨励賞

  2004年

  受賞区分： 国内学会・会議・シンポジウム等の賞

担当授業科目 【 表示 ／ 非表示 】

担当授業科目 【 表示 ／ 非表示 】

• 課題研究（天然医薬資源学）

  2024年度

• 演習（天然医薬資源学）

  2024年度

• 卒業研究１（薬学科）

  2024年度

• 生薬学実習

  2024年度

• 生薬学２

  2024年度

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