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山本 英樹Hideki Yamamoto

教授：山本 英樹

研究内容・メッセージ

私はWnt（ウィント）と呼ばれる細胞外分泌蛋白質がいかにして細胞膜において受容され、シグナルを細胞内に伝達し、細胞応答を制御するかを生化学的解析によって研究してきました。これまでの経験を活かして、生物の複雑な生命現象を分子レベルで解明し、生体が恒常性を保つ仕組みを明らかにしたいと考えています。また、生化学の講義と基礎医学実習を通じて、医療従事者として必要な基礎知識の習得に貢献したいと考えています。

職位
教授
学位・資格
博士（医学）
専門領域・分野
生化学、細胞生物学、基礎医学
担当科目
基礎ゼミⅠ・Ⅱ、基礎化学、基礎医学実習、生化学、専門ゼミⅠ・Ⅱ・Ⅲ・Ⅳ、卒業研究

略歴

1995年神戸大学理学部生物学科卒、1997年同大学大学院自然科学研究科生物学専攻修了、2001年広島大学大学院医学系研究科修了（博士（医学））。2001年日本学術振興会特別研究員PD（広島大学大学院医歯薬学総合研究科）、2003年広島大学大学院医歯薬学総合研究科助手、2007年助教、同年准教授。2009年大阪大学大学院医学系研究科准教授。2021年より本学教授。

社会活動等

所属学会／日本分子生物学会、日本癌学会、日本生化学会

著書等

  • Kikuchi A, Yamamoto H, Sato A, Matsumoto S：Wnt5a: its signalling, functions, and implication in diseases. Acta physiol. 204：17-33, 2012
  • Kikuchi A, Yamamoto H, Sato A, Matsumoto S：New insights into the mechanism of Wnt signaling pathway activation. Int. Rev. Cell Mol. Biol. 291：21-71, 2011
  • Kikuchi A, Yamamoto H, Sato A：Selective activation of mechanisms of Wnt signaling pathways. Trends Cell Biol. 19：119-129, 2009
  • Kikuchi A, Yamamoto H：Tumor formation due to abnormalities in the β-catenin-independent pathway of Wnt signaling. Cancer Sci. 99：202-208, 2008
  • Kikuchi A, Yamamoto H：Regulation of Wnt signalling by receptor-mediated endocytosis. J. Biochem. (Tokyo) 141：443-451, 2007
  • Kikuchi A, Yamamoto H, Kishida S：Multiplicity of the interactions of Wnt proteins and their receptors. Cell. Signal. 19：659-671, 2007
  • Kikuchi A, Kishida S, Yamamoto H：Regulation of Wnt signaling by protein-protein interaction and post-translational modifications. Exp. Mol. Med. 38：1-10, 2006
  • 山本英樹、菊池章：GPCR研究の最前線2016「WntシグナルにおけるFrizzled受容体の活性化機構」医学のあゆみ 256：421-429, 2016
  • 山本英樹、菊池章：Wntの脂質修飾を標的にしたがん創薬 The Lipid 25：443-450, 2014
  • 山本英樹、菊池章：極性化上皮細胞におけるWntの分泌制御 細胞工学 32：388-395, 2013
  • 山本英樹、菊池章：Wntシグナル経路の多様性と選択的活性化 医学のあゆみ 233： 948-954, 2010
  • 山本英樹：Wntシグナル伝達経路の活性制御と発がんとの関連 生化学 80：1079-1093, 2008
  • 山本英樹、日野真一郎、菊池章：リン酸化修飾を介するWntシグナルネットワークによる細胞応答 実験医学 23：1993-1998, 2005
  • 山本英樹、菊池章：エンドサイトーシスによるWntシグナル伝達の制御 細胞工学23：637-641, 2004
  • 山本英樹、池田聡、菊池章：Wntシグナル伝達の制御機構と発癌との関連 Molecular medicine 39：1264-1272, 2002
  • 山本英樹、菊池章：Wntシグナル伝達経路と癌化とのかかわり BIO Clinica 17：459-463, 2002
  • 井原基公、山本英樹、菊池章：Wntシグナルとβ-カテニン 血液・腫瘍科 44：496-504, 2002
  • 丹治知恵、山本英樹、菊池章：Axinを介するWntシグナル伝達経路の制御機構 遺伝子医学 5：257-264, 2001
  • 山本英樹、岸田昭世、菊池章：Wntシグナル伝達抑制因子Axinによるβカテニン分解制御機構 G.I. Research 7：72-77, 1999

主な研究実績

  • Sada R, Kimura H, Fukata Y, Fukata M, Yamamoto H, Kikuchi A：Dynamic palmitoylation controls the microdomain localization of the DKK1 receptors CKAP4 and LRP6. Sci. Signal 19(608)：eaat9519, 2019
  • Kimura H, Yamamoto H, Harada T, Fumoto K, Osugi Y, Sada R, Maehara N, Hikita H, Mori S, Eguchi H, Ikawa M, Takehara T, Kikuchi A：Clin. CKAP4, a DKK1 receptor, is a biomarker in exosomes derived from pancreatic cancer and a molecular target for therapy. Cancer.Res 25：1936-1947, 2019
  • Kobayashi Y, Kadoya T, Amioka A, Hanaki H, Sasada S, Masumoto N, Yamamoto H, Arihiro K, Kikuchi A, Okada M：Wnt5a-induced cell migration is associated with the aggressiveness of estrogen receptor-positive breast cancer．Oncotarget 9：20979-20992, 2018
  • Yamamoto H, Sato A, Kikuchi A：Apical secretion of Wnt1 in polarized epithelial cells is regulated by exocyst-mediated trafficking. J. Biochem. (Tokyo) 162：317-326, 2017
  • #Yamamoto H, #Umeda D, Matsumoto S, Kikuchi A(# equal contribution)：LDL switches the LRP6 internalization route from flotillin-dependent to clathrin-dependent in hepatic cells. J. Cell Sci. 130：3542-3556, 2017
  • Harada T, Yamamoto H, Kishida S, Kishida M, Awada C, Takao T,　Kikuchi　A：Wnt5b-associated exosomes promote cancer cell migration and proliferation.　 Cancer Sci. 108：42-52, 2017
  • Lim BC, Matsumoto S, Yamamoto H, Mizuno H, Kikuta J, Ishii M, Kikuchi A：Prickle1 promotes focal adhesion disassembly in cooperation with the CLASP-LL5β complex in migrating cells．J. Cell Sci. 129：3115-3129, 2016
  • Mihara E, Hirai H, Yamamoto H, Tamura-Kawakami K, Matano M, Kikuchi A, Sato T, Takagi J：Active and water-soluble form of lipidated Wnt protein is maintained by a serum glycoprotein afamin/α-albumin. eLife 5：e11621, 2016
  • Yamamoto H, Awada C, Matsumoto S, Kaneiwa T, Sugimoto T, Takao T, Kikuchi A：Basolateral secretion of Wnt5a in polarized epithelial cells is required for apical lumen formation. J. Cell Sci. 128：1051-1063, 2015
  • Shojima K, Sato A, Hanaki H, Tsujimoto I, Nakamura M, Hattori K, Sato Y, Dohi K, Hirata M, Yamamoto H, Kikuchi A：Wnt5a promotes cancer cell invasion and proliferation by receptor-mediated endocytosis-dependent and -independent mechanisms, respectively. Sci. Rep. 5：8042, 2015
  • Yamamoto H, Awada C, Hanaki H, Sakane H, Tsujimoto I, Takahashi Y, Takao T, Kikuchi A：Apical and basolateral secretion of Wnt11 and Wnt3a in polarized epithelial cells. J. Cell Sci. 126：2931-2943, 2013
  • Hanaki H, Yamamoto H, Sakane H, Matsumoto S, Ohdan H, Sato A, Kikuchi A：An Anti-Wnt5a antibody suppresses metastasis of gastric cancer cells in vivo by inhibiting receptor-mediated endocytosis. Mol. Cancer Ther. 11：298-307, 2012
  • Sakane H, Yamamoto H, Matsumoto S, A, Kikuchi A：Localization of glypican-4 in different membrane microdomains is involved in the regulation of Wnt signaling. J. Cell Sci. 125：449-460, 2012
  • Kagermeier-Schenk B, Wehner D, Ozhan-Kizil G, Yamamoto H, Li J, et al.：The transmembrane protein Waif1/5T4 inhibits Wnt/β-catenin signaling and activates noncanonical Wnt pathways by modifying LRP6 subcellular localization. Dev. Cell 21：1129-1143, 2011
  • Sato A, Yamamoto H, Sakane H, Koyama H, Kikuchi A：Wnt5a regulates distinct signalling pathways by binding to Frizzled2. EMBO J. 29：41-54, 2010
  • Sakane, H., Yamamoto, H., Kikuchi, A：LRP6 is internalized by Dkk1 to suppress its phosphorylation in the lipid raft and is recycled for reuse. J. Cell Sci. 123 : 360-368, 2010
  • Yamamoto H, Oue N, Sato A, Hasegawa Y, Yamamoto H, Matsubara A, Yasui W, Kikuchi, A：Wnt5a signaling is involved in the aggressiveness of prostate cancer and expression of metalloproteinase. Oncogene 29：2036-2046, 2010
  • Yamamoto H, Kitadai Y, Yamamoto H, Oue N, Ohdan H, Yasui W, Kikuchi A：Laminin 2 mediates Wnt5a-induced invasion of gastric cancer cells. Gastroenterology 137：242-252, 2009
  • Yamamoto H, Sakane H, Yamamoto H, Michiue T, Kikuchi, A：Wnt3a and Dkk1 regulate distinct internalization pathways of LRP6 to tune the activation of β-catenin signaling. Dev. Cell 15：37-48, 2008
  • Kurayoshi M, Yamamoto H, Izumi S, Kikuchi A : Post-translational palmitoylation and glycosylation of Wnt-5a are necessary for its signaling. Biochem. J. 402：515-523, 2007
  • Komekado H, Yamamoto H, Chiba T, Kikuchi A：Glycosylation and palmitoylation of Wnt-3a are coupled to produce an active form of Wnt-3a. Genes Cells 4：521-534, 2007
  • Shibata N, Tomimoto Y, Hanamura T, Yamamoto R, Ueda M, Ueda Y, Mizuno N, Ogata H, Komori H, Shomura Y, Kataoka M, Shimizu S, Kondo J, Yamamoto H, Kikuchi A, Higuchi Y：Crystallization and preliminary X-ray crystallographic studies of the axin DIX domain. Acta. Crystallogr. Sect. F. Struct. Biol. Cryst. Commun. 63：529-531, 2007
  • Yamamoto H, Komekado H, Kikuchi A：Caveolin is necessary for Wnt-3a-dependent internalization of LRP6 and accumulation of β-catenin. Dev. Cell 11：213-223, 2006
  • Kurayoshi M, Oue N, Yamamoto H, Kishida M, Inoue A, Asahara T, Yasui W, Kikuchi A：Expression of Wnt-5a is correlated with aggressiveness of gastric cancer by stimulating cell migration and invasion. Cancer Res. 66：10439-10448, 2006
  • Yamashina K, Yamamoto H, Chayama K, Nakajima K, Kikuchi A：Suppression of STAT3 activity by Duplin, which is a negative negulator of the Wnt signal. J. Biochem. (Tokyo) 139：305-314, 2006
  • Ihara M, Yamamoto H, Kikuchi A：SUMO-1 modification of PIASy, an E3 ligase, is necessary for PIASy-dependent activation of Tcf-4. Mol. Cell. Biol. 25：3506-3518, 2005
  • Kishida S, Yamamoto H, Kikuchi, A：Wnt-3a and Dvl induce neurite retraction by activating Rho-associated kinase. Mol. Cell. Biol. 24：4487-4501, 2004
  • Komatsu T, Mizusaki H, Mukai T, Ogawa H, Baba D, Shirakawa M, Hatakeyama S, Nakayama KI, Yamamoto H, Kikuchi A, Morohashi K：Small ubiquitin-like modifier 1 (SUMO-1) modification of the synergy control motif of Ad4 binding protein/steroidogenic factor 1(Ad4BP/SF-1) regulates synergistic transcription between Ad4BP/SF-1 and Sox9. Mol. Endocrinol. 18：2451-2462, 2004
  • Yukita A, Michiue T, Fukui A, Sakurai K, Yamamoto H, Ihara M, Kikuchi A, Asashima M：XSENP1, a novel sumo-specific protease in Xenopus, inhibits normal head formation by down-regulation of Wnt/β-catenin signalling. Genes Cells 9：723-736, 2004
  • Yamamoto H, Ihara M, Matsuura Y, Kikuchi A：Sumoylation is involved in β-catenin-dependent activation of Tcf-4. EMBO J. 22：2047-2059, 2003
  • Kadoya T, Yamamoto H, Suzuki T, Yukita A, Fukui A, Michiue T, Asashima M, Tanaka K, Asashima M, Kikuchi A：Desumoylation activity of Axam, a novel Axin-binding protein, is involved in downregulation of β-catenin. Mol. Cell. Biol. 22：3803-3819, 2002
  • Tanji C, Yamamoto H, Yorioka N, Kohno N, Kikuchi K, Kikuchi A：A-kinase anchoring protein AKAP220 binds to glycogen synthase kinase-3β (GSK-3β) and mediates protein kinase A-dependent inhibition of GSK-3β. J. Biol. Chem. 277：36955-39561, 2002
  • Yamamoto H, Hinoi T, Fukui A, Michiue T, Usui H, Janssens V, Van Hoof C, Goris J, Asashima M, Kikuchi A：Inhibition of the Wnt signaling pathway by the PR61 subunit of protein phosphatase 2A. J. Biol. Chem. 276：26875-26882, 2001
  • Kishida M, Hino S-I, Michiue T, Yamamoto H, Kishida S, Fukui A, Asashima M, Kikuchi A：Synergistic activation of the Wnt signaling pathway by Dvl and casein kinase Iε. J. Biol. Chem. 276：33147-33155, 2001
  • Furuhashi M, Yagi K, Yamamoto H, Furusawa Y, Shimada S, Nakamura Y, Kikuchi A, Miyazono K, Kato M：Axin facilitates Smad3 activation in transforming growth factor-β　signaling. Mol. Cell. Biol. 21：5132-5141, 2001
  • Sakamoto I, Kishida S, Fukui A, Kishida M, Yamamoto H, Hino S-I, Michiue T, Takada S, Asashima M, Kikuchi, A：A novel β-catenin binding protein inhibits β-catenin-dependent Tcf activation and axis formation. J. Biol. Chem. 275：32871-32878, 2000
  • Yamamoto H, Hinoi T, Kishida M, Takada S, Kishida S, Kikuchi A：Complex formation of adenomatous polyposis coli gene product and Axin facilitates glycogen synthase kinase-3β-dependent phosphorylation of β-catenin and downregulates β-catenin. J. Biol. Chem. 275：34399-34406, 2000
  • Yamamoto H, Kishida S, Kishida M, Ikeda S, Takada S, Kikuchi A： Phosphorylation of Axin, a Wnt signal negative regulator, by glycogen synthase kinase-3β regulates its stability. J. Biol. Chem. 274：10681-10684, 1999
  • Kishida S, Yamamoto H, Hino S, Ikeda S, Kishida M, Kikuchi A：DIX domains of Dvl and Axin are necessary for protein interactions and their ability to regulate β-catenin stability. Mol. Cell. Biol. 19：4414-4422, 1999
  • Ikeda S, Kishida S, Yamamoto H, Murai H, Koyama S, Kikuchi A.：Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3β and β-catenin and promotes GSK-3β-dependent phosphorylation of β-catenin. EMBO J. 17：1371-1384, 1998
  • Yamamoto H, Kishida S, Uochi T, Ikeda S, Koyama S, Asashima M, Kikuchi A： Axil, a member of the Axin family, interacts with both glycogen synthase kinase 3β and β-catenin and inhibits axis formation of Xenopus embryos. Mol. Cell. Biol. 18：2867-2875, 1998
  • Kishida S, Yamamoto H, Ikeda S, Kishida M, Sakamoto I, Koyama S, Kikuchi, A：Axin, a negative regulator of the Wnt signaling pathway, directly interacts with adenomatous polyposis coli and regulates the stabilization of β-catenin. J. Biol. Chem. 273：10823-10826, 1998
  • Sato K, Yamamoto H, Otsuki, T, Aoto M, Tokmakov AA, Hayashi F, Fukami Y： Phosphatidylinositol 4,5-bisphosphate stimulates phosphorylation of the adaptor protein Shc by c-Src. FEBS Lett. 410：136-140, 1997

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