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University of Tsukuba, Laboratory of Fungal Interaction and Molecular Biology

メンバーMEMBERS

 萩原大祐(HAGIWARA, Daisuke)・准教授



主な研究テーマ

  • 糸状菌と他生物との相互作用応答とそのメカニズムの解明
  • 病原糸状菌の薬剤応答と薬剤耐性機構の解明
  • 糸状菌の二次代謝物、酵素ライブラリーの創成
  • 糸状菌由来トキシン(カビ毒)の抑制技術の開発

連絡先

E-mail : hagiwara.daisuke.gb(at)u.tsukuba.ac.jp
    ※(at)を@にかえてください。

学歴

2006年 名古屋大学大学院 生命農学研究科 生物機構・機能科学専攻卒業(博士後期課程)
2003年 名古屋大学大学院 生命農学研究科 生物機構・機能科学専攻卒業(博士前期課程)
2000年 早稲田大学 理工学部 応用化学科卒業

職歴

2017年〜 現職
2011年〜2017年 千葉大学 真菌医学研究センター 特任助教
2010年~2011年 デンソー株式会社/中央大学 理工学部 博士研究員/機構助教
2007年~2010年 日本学術振興会 特別研究員 (東北大学 未来科学技術共同研究センター)
2006年~2007年 名古屋大学 農学部 博士研究員
2000年 一般企業

受賞歴

1. 2016年 日本医真菌学会学術集会、優秀演題賞(発表者)
2. 2015年 日本医真菌学会学術集会、優秀演題賞(発表者)
3. 2015年 真菌症フォーラム、奨励賞(発表者)
4. 平成24年度 糸状菌遺伝子研究会 奨励賞
5. 2004年度 日本農芸化学会 BBB論文賞(筆頭筆者)



研究業績

論文  総説・解説  著書  特許  招待講演  


論文
  1. Hagiwara D, Arai T, Takahashi H, Kusuya Y, Watanabe A*, Kamei K: Non-cyp51A azole-resistant Aspergillus fumigatus isolates with mutation in HMG-CoA reductase. Emerg. Infect. Dis., in press

  2. Hagiwara D*, Takahashi H, Takagi H, Watanabe A, Kamei K: Heterogeneity in pathogenicity-related properties and stress tolerance in Aspergillus fumigatus clinical isolates. Med. Mycol. J., in press

  3. Takahashi-Nakaguchi A, Sakai K, Takahashi H, Hagiwara D, Toyotome T, Chibana H, Watanabe A, Yaguchi T, Yamaguchi M, Kamei K, Gonoi T*: Aspergillus fumigatus adhesion factors in dormant conidia revealed through comparative phenotypic and transcriptomic analyses. Cell. Microbiol., 3: e12802 (2018)

  4. Toyotome T*, Hagiwara D, Watanabe A, Kamei K: A simple method to detect the tandem repeat of the cyp51A promoter in azole-resistant strains of Aspergillus fumigatus. Med. Mycol., in press

  5. Takahashi H*, Kusuya Y, Hagiwara D, Takahashi-Nakaguchi A, Sakai K, Gonoi T: Global gene expression reveals stress-responsive genes in Aspergillus fumigatus mycelia. BMC Genomics, 18: 942 (2017)

  6. Hashimoto A, Hagiwara D, Watanabe A*, Yahiro M, Yikelamu A, Yaguchi T, Kamei K: Drug sensitivity and resistance mechanism in Aspergillus section Nigri strains from Japan. Antimicrob. Agents Chemother., 61: e02583-16 (2017)

  7. Kusuya Y, Hagiwara D, Sakai K, Yaguchi T, Gonoi T, Takahashi H*: Transcription factor Afmac1 controls copper import machinery in Aspergillus fumigatus. Curr. Gent., 63: 777-789 (2017)

  8. Toyotome T*, Hagiwara D, Kida H, Ogi T, Watanabe A, Wada T, Komatsu R, Kamei K: First clinical isolation report of azole-resistant Aspergillus fumigatus with TR34/L98H-type mutation in Japan. J. Infect. Chemother., 23: 579-581 (2017)

  9. Hagiwara D*, Sakai K, Suzuki S, Umemura M, Nogawa T, Kato N, Osada H, Watanabe A, Kawamoto S, Gonoi T, Kamei K: Temperature during conidiation affects stress tolerance, pigmentation, and trypacidin accumulation in the conidia of the airborne pathogen Aspergillus fumigatus. PLoS One, 12: e0177050 (2017)

  10. Onishi K, Sarumoh BM, Hagiwara D, Kamei K, Toyotome T*: Azole-resistant Aspergillus fumigatus containing a 34-bp tandem repeat in cyp51A promoter is isolated from the environment in Japan. Med. Mycol. J., 58E: E67-E70 (2017)

  11. Silva LP, de Castro PA, Dos Reis TF, Paziani MH, Kress MR, Riaño-Pachón DM, Hagiwara D, Ries LN, Brown NA, Goldman GH*: Genome-wide transcriptome analysis of Aspergillus fumigatus exposed to osmotic stress reveals regulators of osmotic and cell wall stresses that are SakAHOG1 and MpkC dependent. Cell. Microbiol., 19: e12681 (2017)

  12. Hagiwara D*, Miura D, Shimizu K, Paul S, Ohba A, Gonoi T, Watanabe A, Kamei K, Shintani T, Moye-Rowley WS, Kawamoto S, Gomi K*: A novel Zn2-Cys6 transcription factor AtrR plays a key role in an azole resistance mechanism of Aspergillus fumigatus by co-regulating cyp51A and cdr1B expressions. PLoS Pathogens, 13: e1006096 (2017)

  13. Hagiwara D*, Watanabe A, Kamei K: Sensitisation of an azole-resistant Aspergillus fumigatus strain containing the Cyp51A-related mutation by deleting the SrbA gene. Scientific Reports, 6: 38833 (2016) 千葉大学ニュースリリース>>こちら

  14. de Castro PA, Dos Reis TF, Dolan SK, Manfiolli AO, Brown NA, Jones GW, Doyle S, Riaño-Pachón DM, Squina FM, Caldana C, Singh A, Del Poeta M, Hagiwara D, Silva-Rocha R, Goldman GH*, The Aspergillus fumigatus SchASCH9 kinase modulates SakAHOG1 MAP kinase activity and it is essential for virulence. Mol. Microbiol., 102: 642-671 (2016)

  15. Hagiwara D*, Takahashi H, Kusuya Y, Kawamoto S, Kamei K, Gonoi T, Comparative transcriptome analysis revealing dormant conidia and germination associated genes in Aspergillus species: An essential role for AtfA in conidial dormancy. BMC Genomics, 17: 358 (2016)

  16. Kunitake E, Hagiwara D, Miyamoto K, Kanamaru K, Kimura M, Kobayashi T*, Regulation of genes encoding cellulolytic enzymes by Pal-PacC signaling in Aspergillus nidulans. Appl. Microbiol. Biotechnol., 100: 3621-3635 (2016)

  17. De Oliveira Bruder-Nascimento AC, Dos Reis TF, de Castro PA, Hori JI, Bom VL, de Assis LJ, Ramalho LN, Rocha MC, Malavazi I, Brown NA, Valiante V, Brakhage AA, Hagiwara D, Goldman GH*, Mitogen activated protein kinases SakAHOG1 and MpkC collaborate for Aspergillus fumigatus virulence. Mol. Microbiol., 100: 841-859 (2016)

  18. Hagiwara D, Takahashi H, Fujimoto M, Sugawara M, Misawa Y, Gonoi T, Itoyama S, Watanabe A*, Kamei K, Multi-azole resistant Aspergillus fumigatus harboring Cyp51A TR46/Y121F/T289A isolated in Japan. J. Infect. Chemother., 22: 577-579 (2016)

  19. Bühler N, Hagiwara D, Takeshita N*, Functional analysis of sterol transporter orthologues (OSHs) in filamentous fungus Aspergillus nidulans. Eukaryot. Cell, 14. 908-921 (2015)

  20. Winkelströter LK, Dolan SK, dos Reis TF, Bom VL, de Castro PA, Hagiwara D, Jones GW, Doyle S, Brown NA, Goldman GH*, Systematic global analysis of genes encoding protein phosphatases in Aspergillus fumigatus. G3, 5. 1525-1539 (2015)

  21. Bom VL, de Castro PA, Winkelströter LK, Marine M, Hori JI, Ramalho LN, dos Reis TF, Goldman MH, Brown NA, Rajendran R, Ramage G, Walker LA, Munro CA, Rocha MC, Malavazi I, Hagiwara D, Goldman GH*, Aspergillus fumigatus sitA phosphatase homologue is important for adhesion, cell wall integrity, biofilm formation and virulence. Eukaryot. Cell, 14. 728-744 (2015)

  22. Takahashi-Nakaguchi A, Muraosa Y, Hagiwara D, Sakai K, Toyotome T, Watanabe A, Kawamoto S, Kamei K, Gonoi T, Takahashi H*, Genome sequence comparison of Aspergillus fumigatus strains isolated from patients with pulmonary aspergilloma and chronic necrotizing pulmonary aspergillosis. Med. Mycol., 53. 353-360 (2015)

  23. Winkelströter LK, Bom VL, de Castro PA, Ramalho LN, Goldman MH, Brown NA, Rajendran R, Ramage G, Bovier E, dos Reis TF, Salvoldi M, Hagiwara D, Goldman GH*, High osmolarity glycerol response (HOG) PtcB phosphatase is important for Aspergillus fumigatus virulence. Mol. Microbiol., 96. 42-54 (2015)

  24. Yoshimi A, Fujioka T, Mizutani O, Marui J, Hagiwara D, Abe K*, Mitogen-activated protein kinases MpkA and MpkB independently affect micafungin sensitivity in Aspergillus nidulans. Biosci. Biotechnol. Biochem., 79. 836-844 (2015)

  25. Shimizu K*, Nakagawa H, Hashimoto R, Hagiwara D, Onji Y, Asano K, Kawamoto S, Takahashi H, Yokoyama K, The α–oxoamine synthase gene fum8 is involved in fumonisin B2 biosynthesis in Aspergillus niger. Mycoscience, 56. 301-308 (2015)

  26. Hagiwara D*, Suzuki S, Kamei K, Gonoi T, Kawamoto S, The role of AtfA and HOG MAPK pathway in stress tolerance in conidia of Aspergillus fumigatus. Fungal Genet. Biol., 73. 138-149 (2014)

  27. Hagiwara D*, Takahashi H, Watanabe A, Takahashi-Nakaguchi A, Kawamoto S, Kamei K, Gonoi T, Whole-genome comparison of Aspergillus fumigatus strains serially isolated from patients infected with aspergillosis. J. Clin. Microbiol., 52. 4202-4209 (2014)

  28. de Castro PA, Chen C, de Almeida RS, Freitas FZ, Bertoloni MC, Morais ER, Brown NA, Ramalho LN, Hagiwara D, Mitchell TK, Goldman GH*, ChIP-seq reveals a role for CrzA in the Aspergillus fumigatus High Osmolarity Glycerol Response (HOG) signaling pathway. Mol. Microbiol., 94. 655-674 (2014)

  29. Hagiwara D*, Takahashi-Nakaguchi A, Toyotome T, Yoshimi A, Abe K, Kamei K, Gonoi T, Kawamoto S, NikA/TcsC histidine kinase is involved in conidiation, hyphal morphology, and responses to osmotic stress and antifungal chemicals in Aspergillus fumigtus. PLoS One, 8. e80881 (2013)

  30. Yoshimi A, Sano M, Inaba A, Kokubun Y, Fujioka T, Mizutani O, Hagiwara D, Fujikawa T, Nishimura M, Yano S, Kasahara S, Shimizu K, Yamaguchi M, Kawakami K, Abe K*, Functional analysis of the α-1,3-glucan synthase genes agsA and agsB in Aspergillus nidulans: AgsB is the major α-1,3-glucan synthase in this fungus. PLoS One, 8. e54893 (2013)

  31. Imamura S*, Hagiwara D, Suzuki F, Kurano N, Harayama S, Genetic transformation of Pseudochoricystis ellipsoidea, an aliphatic hydrocarbon-producing green alga. J. Gen. Appl. Microbiol., 58. 1-10 (2012)

  32. Hagiwara D*, Mizuno T, Abe K*, Characterization of the conserved phosphorylation site in the Aspergillus nidulans response regulator SrrA. Curr. Genet., 57. 103-114 (2011)

  33. Marui J, Yoshimi A, Hagiwara D, Fujii-Watanabe Y, Oda K, Koike H, Tamano K, Ishii T, Sano M, Machida M, and Abe K*, Use of the Aspergillus oryzae actin gene promoter in a novel reporter system for exploring antifungal compounds and their target genes. Appl. Microbiol. Biotechnol., 87. 1829-1840 (2010)

  34. Hagiwara D*, Asano Y, Marui J, Yoshimi A, Mizuno T, Abe K*, Transcriptional profiling for Aspergillus nidulans HogA MAPK signaling pathway in response to fludioxonil and osmotic stress. Fungal Genet. Biol., 46. 868-878 (2009)

  35. Hagiwara D*, Mizuno T, and Abe K*, Characterization of NikA histidine kinase and two response regulators with special reference to osmotic adaptation and asexual development in Aspergillus nidulans. Biosci. Biotechnol. Biochem., 73. 1566-1571 (2009)

  36. Hagiwara D*, Kondo A, Fujioka T, and Abe K*, Functional analysis of C2H2 zinc finger transcription factor CrzA involved in calcium signaling in Aspergillus nidulans. Curr. Genet., 54. 325-338 (2008)

  37. Hagiwara D*, Asano Y, Yamashino T, and Mizuno T, Characterization of bZip-type transcription factor AtfA with reference to stress responses of conidia of Aspergillus nidulans. Biosci. Biotechnol. Biochem., 72. 2756-2760 (2008)

  38. Asano Y, Hagiwara D*, Yamashino T, and Mizuno T, Characterization of the bZip-type transcription factor NapA with reference to oxidative stress response in Aspergillus nidulans. Biosci. Biotechnol. Biochem., 71. 1800-1803 (2007)

  39. Furukawa K, Yoshimi A, Furukawa T, Hoshi Y, Hagiwara D, Sato N, Fujioka T, Mizutani O, Mizuno Y, Kobayashi T, and Abe K*, Novel reporter gene expression systems for monitoring activation of the Aspergillus nidulans HOG pathway. Biosci. Biotechnol. Biochem., 71. 1724-1730 (2007)

  40. Hagiwara D*, Asano Y, Marui J, Furukawa K, Kanamaru K, Kato M, Abe K, Kobayashi T, Yamashino T, and Mizuno T, The SskA and SrrA response regulators are implicated in oxidative stress responses of hyphae and asexual spores in the phosphorelay signaling network of Aspergillus nidulans. Biosci. Biotechnol. Biochem., 71. 1003-1014 (2007)

  41. Hagiwara D*, Matsubayashi Y, Marui J, Furukawa K, Yamashino T, Kanamaru K, Kato M, Abe K, Kobayashi T, and Mizuno T, Characterization of the NikA histidine kinase implicated in the phosphorelay signal transduction of Aspergillus nidulans with special reference to fungicide responses. Biosci. Biotechnol. Biochem., 71. 844-847 (2007)

  42. Hagiwara D, Yamashino T and Mizuno T*, Genome-wide comparison of the His-to-Asp phosphorelay signaling components of three symbiotic genera of Rhizobia. DNA Res., 11. 57-65 (2004)

  43. Hagiwara D, Yamashino T and Mizuno T*, A genome-wide view of Escherichia coli BasS-BasR two-component system implicated in iron-responses. Biosci. Biotechnol. Biochem., 68. 1758-1767 (2004) (2004年度日本農芸化学会 BBB論文賞)

  44. Hagiwara D, Sugiura M, Oshima T, Mori H, Aiba H, Yamashino T and Mizuno T*, Genome-wide analyses revealing a signaling network of the RcsC-YojN-RcsB phosphorelay system in Escherichia coli. J. Bacteriol., 185. 5735-5746 (2003)
    ( * 責任著者)

総説・解説
  1. Hagiwara D*: Current status of azole-resistant Aspergillus fumigatus isolates in East Asia: China, Japan, Korea, and Taiwan. Med. Mycol. J., in press

  2. Toyotome T*, Hagiwara D, Takahashi H, Watanabe A, Kamei K: Emerging antifungal drug resistance in Aspergillus fumigatus and among other species of Aspergillus. Curr. Fungal Infect. Rep., in press

  3. 高橋(中口)梓、萩原大祐、高橋弘喜、酒井香奈江、豊留孝仁、渡辺哲、亀井克彦、五ノ井透、「次世代シーケンサーを活用したオミクス解析によるAspergillus fumigatus病原因子探索」Med. Mycol. J., Review, 59J: J35-J40 (2018)

  4. 萩原大祐、「糸状菌ゲノムから紐解く二次代謝の多様性」JSM Mycotoxins, 68(2):89-92 (2018)

  5. 萩原大祐、「真菌の薬剤耐性機序」化学療法の領域 増刊号「深在性真菌症のすべて」,34(S-1):37-45 (2018)

  6. 高橋(中口)梓、萩原大祐、高橋弘喜、酒井香奈江、豊留孝仁、渡辺哲、亀井克彦、五ノ井透、「次世代シーケンサーを活用したオミクス解析によるAspergillus fumigatus病原因子探索」Med. Mycol. J., Review, 59J: J35-J40 (2018)

  7. 渡辺哲、萩原大祐、亀井克彦、「特集 血液疾患の真菌感染症 2. 薬剤耐性真菌」血液フロンティア 26(12):33-38 (2016)

  8. 萩原大祐、「糸状菌胞子生物学のすすめ〜麹菌から病原菌まで、細胞からゲノムまで〜」温古知新 53:35-42 (2016)

  9. Hagiwara D*, A Watanabe, K Kamei, GH Goldman, Epidemiological and genomic landscape of azole resistance mechanisms in Aspergillus fungi. Front. Microbiol., Review, 7: 1382 (2016)

  10. Hagiwara D, K Sakamoto, K Abe, K Gomi*, Signaling pathways for stress responses and adaptation in Aspergillus species: Stress biology in the post-genomic era. Biosci. Biotechnol. Biochem., Review, 80: 1667-1680 (2016)

  11. 萩原大祐、「真菌感染症分野が直面している薬剤耐性の現状」化学と生物 53(5):277-279 (2015)

  12. 萩原大祐、古川健太郎、阿部敬悦、「Aspergillus属の分生子におけるストレス耐性能と制御機構」日本醸造協会誌 106(10):638-644 (2011)

  13. 萩原大祐、「カビの胞子、長生きの秘訣」日本生物工学会誌 89(4):208 (2011)

  14. 坂本和俊、萩原大祐、阿部敬悦、五味勝也、「種もやしからひろがる糸状菌分生子のストレス耐性機構」化学と生物 47(10):684-689 (2009)


著書
  1. Hagiwara D, Yoshimi A, Sakamoto K, Gomi K, Abe K, “Response and adaptation to cell wall stress and osmotic stress in Aspergillus species” Stress Biology of Yeasts and Fungi. Eds. Takagi H and Kitagaki H, Springer, p199-218 (2015)

  2. 藏野憲秀、萩原大祐、今村壮輔、原山重明、「軽油生産能を有する単細胞緑藻の生産性向上」、 微細藻類によるエネルギー生産と事業展望、シーエムシー出版(2012)

  3. Abe K et al. (12人中4番目) “Novel industrial application of Aspergillus oryzae genomics” Aspergillus: Molecular Biology and Genomics. Eds. Machida M and Gomi K, Caister Academic Press, p199-227 (2010)


特許
  1. 西村麻里江、藤川貴史、森脇明弘、阿部敬悦、吉見啓、萩原大祐、藤岡智則、河合清、「新規レポーター遺伝子を用いたスクリーニング方法」特開 2010-220590、(平成21年3月25日出願、平成22年10月7日公開)


招待講演
  1. 「ゲノム、トランスクリプトーム解析で”視る”糸状菌細胞」2018年度日本農芸化学会大会,名古屋,名城大学,Mar. 2018

  2. 「アスペルギルス属菌のアゾール薬応答機構の解明:耐性菌治療法へのヒント」第91回日本細菌学会総会,福岡,福岡国際会議場,Mar. 2018

  3. 「糸状菌を取り巻くミクロコスモス」筑波大学糸状菌相互応答講座開設記念シンポジウム,つくば,筑波大学,Jan. 2018

  4. 「糸状菌ゲノムから紐解く二次代謝の多様性」日本マイコトキシン学会第81回学術講演会,東京,東京理科大学,Jan. 2018

  5. 「糸状菌に見出されたエルゴステロール合成経路を制御する新規転写因子〜Fungal infectionの制御にむけて」ConBio2017, 神戸, 神戸ポートアイランド, Dec. 2017

  6. 「薬剤耐性の最前線」第61回日本医真菌学会学術集会,金沢,ホテル金沢,Oct. 2017

  7. 「真菌のゲノム情報からChemotaxonomyを考える」第61回日本医真菌学会学術集会,金沢,ホテル金沢,Sep. 2017

  8. 「糸状菌の薬剤応答機構を統御する転写因子の発見」 第192回 酵母細胞研究会例会, 東京, 東大, Jul. 2017

  9. 「ポスト・ポストゲノム時代の糸状菌分子生物学を支えるAspergillus fumigatusの遺伝子・ゲノム研究」糸状菌分子生物学コンファレンス,第15回記念特別シンポジウム,東京都,ルミエール府中,Nov. 2015

  10. Aspergillus fumigatusのアゾール薬耐性に関与する新規転写制御因子AtrRの機能解析 —迫り来るアゾール薬耐性株に備えた研究」第五回千葉県真菌症研究会学術講演会, 千葉市, ホテルニューオータニ幕張, Jun. 2015

  11. 「カビ胞子のストレス耐性機構の解明をめざして」糸状菌分子生物研究会若手の会 第一回 ワークショップ, つくば, 文部科学省研究交流センター, Nov. 2013

  12. 「糸状菌の二成分情報伝達経路を構成する遺伝子群の機能解析」糸状菌遺伝子研究会例会, 東京都北区,北とぴあ,Jun. 2012

  13. ‘Signal transduction systems involved in responses to fungicide in Aspergillus nidulans,’ Asian Mycological Congress, Taichung, Taiwan, Nov. 2009


バナースペース

筑波大学 糸状菌相互応答講座

〒305-8577
茨城県つくば市天王台1-1-1
生物農林学系棟
B211, B212, F209

TEL:
029-853-2672(萩原 B212)
029-853-6636(浦山 B211)