トップページ研究室紹介(基礎医学領域)生物化学 分子細胞化学(生化学第二)

生物化学

分子細胞化学(生化学第二)

分野の概要

癌細胞、神経細胞を対象に、糖タンパク質、糖脂質による細胞の増殖、分化、死などの細胞運命の調節機構を解明し、その知見をふまえた難治疾患の新規治療法の開発を目指している。


研究プロジェクト
 1.糖鎖合成酵素遺伝子のクローニング
 2.糖脂質、糖タンパク質糖鎖による癌と増殖と転移のシグナル調節
 3.神経系細胞の増殖、分化、アポトーシスのシグナル解析
 4.糖鎖変異マウスの作成と異常表現型の及びその分子機構の解析
 5.神経変性機構の解析と神経再生遺伝子のクローニング
 6.癌の悪性形質と転移に関わる遺伝子の同定とメカニズムの解明
 7.癌の抗体・遺伝子治療の開発

研究室ホームページへ

教員

構成員名/英名表記 役職 所属
古川 鋼一/FURUKAWA Koichi
詳しくはこちら→
教授分子細胞化学/機能分子制御学
岡島 徹也/OKAJIMA Tetsuya
詳しくはこちら→
准教授分子細胞化学/機能分子制御学
山内 祥生/YAMAUCHI Yoshio
詳しくはこちら→
講師分子細胞化学/機能分子制御学

研究分野紹介

専攻 分子総合医学専攻
大講座 生物化学講座
分野 分子細胞化学/機能分子制御学分野
ユニット名 生化学第2

研究キーワード

癌、細胞増殖、分化、糖鎖、糖脂質、O型糖鎖、糖転移酵素、糖鎖シグナル、リン酸化,神経変性、脂質ラフト、抗体治療、癌幹細胞

最近の研究業績

[2008年]
Matsuura, A., Ito, M., Sakaidani, Y., Kondo, T., Murakami, K., Furukawa, K., Nadano, D., Matsuda, T. and Okajima, T.: A novel O-GlcNAc modification on Notch receptors. O-linked GlcNAc is present on the extracellular domain of Notch receptors. J. Biol. Chem. in press
Tajima, O., Egashira, N., Ohmi, Y., Fukue, Y., Mishima, K., Iwasaki, K., Fujiwara, M., Sugiura, Y., Furukawa, K., Furukawa, K.: Reduced motor and sensory functions and emotional response in GM3-only mice: emergence from early stage of life and exacerbation with aging. Behavioural Brain Research. in press
Kondo, Y., Tokuda, N., Fan, X., Yamashita, T., Honke, K., Takematsu, H., Togayachi, A., Ohta, M., Kotzusumi, Y., Suzuki, A., Narimatsu, H., Tajima, O., Furukawa, K., Furukawa, K.: Glycosphingolipids are not pivotal receptors for Subtilase cytotoxin in vivo: Sensitivity analysis with glycosylation-defective mutant mice. Biochem. Biophys. Res. Commun. in press
Furukawa, K., Tsuchida, A., Okajima, T., Furukawa, K.: Glycoconjugate glycosyltransferases. Glycoconj. J. in press
Ohkawa, Y., Miyazaki, S., Miyata, M., Hamamura, K., Furukawa, K., Furukawa, K.: Essential roles of integrin-mediated signaling for the enhancement of malignant properties of melanomas based on the expression of GD3. Biochem. Biophys. Res. Commun. in press
Furukawa, K., Hamamura, K., Nakashima, H., Furukawa, K.: Molecules in the signaling pathway activated by gangliosides can be targets of therapeutics for malignant melanomas. Proteomics. in press
Furukawa, K., Aixinjueluo, W., Kasama, T., Ohkawa, Y., Yoshihara, M., Ohmi, Y., Tajima, O., Suzumura, A., Kittaka, D., and Furukawa, K.: Disruption of GM2/GD2 synthase gene resulted in neo-expression of 9-O-acetyl GD3 irrespective of Tis21. J. Neurochem. 105, 1057-1066, 2008
Kittaka, D., Itoh, M., Ohmi, Y., Kondo, Y., Fukumoto, S., Urano, T., Tajima, O., Furukawa, K., and Furukawa, K.: Impaired hypoglossal nerve regeneration in complex ganglioside-lacking mutant mice: down-regulation of neurotrophic factors and receptors as possible mechanisms. Glycobiology 18, 509-516, 2008
Hamamura, K., Tsuji, M., Nakashima, H., Miyazaki, S., Urano, T., Yamamoto, N., Ueda, M., Furukawa, K., and Furukawa, K.: Focal adhesion kinase as well as p130Cas and paxillin is crucially involved in the enhanced malignant properties under expression of ganglioside GD3 in melanoma cells. Biochim. Biophys. Acta 1780, 513-519, 2008
Kondo, Y., Shen, L., Cheng, A., Ahmed, S., Boumber, Y., Charo, C., Yamochi, T., Urano, T., Furukawa, K., Kwabi-Addo, B., Gold, D.L., Sekido, Y., Huang, H.-M.,T., Issa, J.-P.J.: Gene silencing in cancer by histone H3 lysine 27 tri-methylation independent of promoter DNA methylation. Nat. Genet. 40: 741-750, 2008
Matsumoto, Y., Yuki, N., Van Kaer, L., Furukawa, K., Hirata, K., and Sugita, M.: Guillain-Barre syndrome-associated IgG responses to gangliosides are generated independently of CD1 function in mice. J. Immunol. 180(1):39-43, 2008


[2007年]
Nakashima, H., Hamamura, K., Mitsudo, K., Tohnai, I., Ueda, M., Urano, T., Furukawa, K., and Furukawa, K.: Overexpression of caveolin-1 in a human melanoma cell line resulted in the dispersion of ganglioside GD3 from lipid rafts and the alteration of leading edge formation, leading to the attenuation of malignant properties. Cancer Sci 98, 512-520, 2007
Uetani, T., Yamashita, D., Shimizu, J., Misawa, H., Tatematsu, Y., Hamaguchi, Y., Miyasaka, T., Katanosaka, Y., Kato, T., Matsubara, T., Furukawa, K., Murohara, T., Takaki, M., and Nakayama, S.: Heart Slice NMR. Heart and Circulatory Physiology 292(2):H1181-1186, 2007
Senda, M., Ito, A., Tsuchida, A., Nakamura, Y., Kasama, K., Kiso, M., Katagiri, Y., Yoshikawa, K., Ono, Y., Ogiso, M., Urano, T., Furukawa, K., Oshima, S., and Furukawa, K.: Identification and expression of a sialyltransferase responsible for the synthesis of disialylgalactosylgloboside in normal and malignant kidney cells: Down-regulation of ST6GalNAc VI in renal cancers. Biochem. J. 402, 459-470, 2007
Susuki, K., Baba, H., Tohyama, K., Kanai, K., Kuwabara, S., Hirata, K, Furukawa, K., Furukawa, K., Rasband, M.N., Yuki, N.: Gangliosides contribute to stability of paranodal junctions and ion channel clusters in myelinated nerve fibers. Glia 55, 746-757, 2007
Yamauchi Y, Reid PC, Sperry JB, Furukawa K, Takeya M, Chang CC, Chang TY.: Plasma membrane rafts complete cholesterol synthesis by participating in retrograde movement of precursor sterols. J. Biol. Chem. 282, 34994-35004, 2007
Takemoto, A., Murayama, A., Katano, M., Urano, T., Furukawa, K., Yokoyama, S., Yanagisawa, J., Hanaoka, F., Kimura, K.: Analysis of the role of Aurora B on the chromosomal targeting of condensin I. Nucleic Acids Res. 35, 2403-2412, 2007
Fujita A, Cheng J, Hirakawa M, Furukawa K, Kusunoki S, Fujimoto T.: Gangliosides GM1 and GM3 in the living cell membrane form clusters susceptible to cholesterol depletion and chilling. Mol. Biol. Cell, 18, 2112-2122, 2007


[ 2006年 ]
Okuda, T., Tokuda, N., Numata, S., Ito, M., Ohta, M., Kawamura, K., Wiels, J., Urano, T., Tajima, O., Furukawa, K., and Furukawa, K.: Targeted disruption of Gb3/CD77 synthase gene resulted in the complete deletion of globo-series glycosphingolipids and loss of sensitivity to verotoxins. J. Biol. Chem. 281:10230-10235, 2006
Ohashi, S., Sakashita, G., Ban, R., Nagasawa, M., Matsuzaki, H., Murata, Y., Taniguchi, H., Shima, H., Furukawa, K. and Urano, T.: Phospho-regulation of human Protein Kinase Aurora-A: Analysis using anti-phospho-Thr288 monoclonal antibodies. Oncogene, in press.
Zhang, Q., Furukawa, K., Chen, Ho-H., Fujinawa, R., Kozutsumi, Y., Suzuki, A., Urano, T., and Furukawa, K.: Down-regulation of caveolin-1 in mouse Lewis lung cancer P29 is a causal factor for the malignant properties in a high-metastatic subline. Oncol. Rep. in press
Ko, K., Furukawa, K., Takahashi, T., Urano, T., Sanai, Y., Nagino, M., Nimura, Y. and Furukawa, K.: Fundamental study of small interfering RNAs for ganglioside GD3 synthase gene as a therapeutic target of lung cancers. Oncogene in press
Zhang, Q., Furukawa, K., Chen, H.-H., Sakakibara, T., Urano, T., and Furukawa, K.: Metastatic potential of mouse Lewis lung cancer cells is regulated via ganglioside GM1 by modulating the matrix metalloprotease-9 localization in lipid rafts. J. Biol. Chem. in press
Goto, H., 1, Kiyono, T., Tomono, Y., Kawajiri, A., Urano, T., Furukawa, K., Nigg, E.A., and Inagaki, M.: Complex Formation of Plk1 and INCENP Required for Metaphase-Anaphase Transition. Nature Cell Biology 8, 180-187, 2006


[ 2005年 ]
Kamimura Y, Furukawa1, K., Kittaka, D., Nishio, M., Hamamura, K., Fukumoto, S., and Furukawa, K.: Differential enhancing effects of α2,8-sialyltransferase on the cell proliferation and mobility. Int. J. Oncol. 26, 337-344, 2005
Nishio, M., Tajima, O., Furukawa1, K., Urano, T. and Furukawa, K.: Over-expression of GM1 enhances the cell proliferation with epidermal growth factor without affecting the receptor localization in the microdomain in PC12 cells. Int. J. Oncol. 26, 191-9, 2005
Hamamura, K., Tanahashi, K., Furukawa, K., Hattori, T., Mizutani, H., Ueda, M., Urano, T., and Furukawa, K.: GM1 expression in H-ras-transformed NIH3T3 results in the suppression of cell proliferation inducing the partial transfer of activated H-ras from non-raft to raft fraction. Int. J. Oncol. 26, 897-904, 2005
Goodfellow, J., Bowes, Tyrone, S., Kazim, Odaka, M., Halstead, S.K., Humphreys, P.D., Wagner, E., Yuki, N., Furukawa, K., Furukawa, K., Plomp, J.J., Willison, H.J.:Over-expression of GD1a ganglioside sensitizes motor nerve terminals to anti-GD1a antibody mediated injury in a model of acute motor axonal neuropathy. J. Neurosci. 25, 1620-1628、2005
Kitamura, M., Igimi, S., Furukawa, K., Furukawa, K.: Different response of the knockout mice lacking b-series gangliosides against botulinum and tetanus toxins. Biochim. Biophys. Acta 1741, 1-3, 2005
Aixinjueluo, W., Furukawa, K., Zhang, Q., Hamamura, K., Tokuda, N., Yoshida, S., Ueda, R., and Furukawa, K.: Mechanisms for the apoptosis of small cell lung cancer cells induced by anti-GD2 monoclonal antibodies: Roles of anoikis. J. Biol. Chem. 280, 29828-29836, 2005
Hamamura, K., Furukawa, K., Hayashi. T., Hattori, T., Nakano, J., Nakashima, H., Okuda, T., Mizutani, H., Hattori, H., Ueda, M., Urano, T., Lloyd, K.O., and Furukawa, K.: Ganglioside GD3 promotes cell growth and invasion through p130Cas and paxillin in malignant melanoma cells. Proc. Natl. Acad. Sci. USA 102, 11041-11046, 2005
Sugiura, Y., Furukawa, K., Tajima, O., Mii, T. Honda, T., and Furukawa, K.: Sensory nerve-dominant nerve degeneration and remodeling in the mutant mice lacking complex gangliosides. Neuroscience 135, 1167-1178, 2005
Boffey, J., Odaka, M., Nicoll, D., Wagner, E.R., Townson, K., Bowes, T., Conner, J., Furukawa, K., Willison, H.J.: Characterisa-tion of the immunoglobulin variable region gene usage encoding the murine anti-ganglioside antibody repertoire. J. Neuroimmunol. 165, 92-103, 2005
Tsuchida, A., Ogiso, M., Nakamura, Y., Furukawa, K., Furukawa, K: Molecular cloning and expression of human ST6GalNAc III: Restricted tissue distribution and substrate specificity. J. Biochem.(Tokyo) 138, 237-243, 2005
Fujii, Y., Numata, S., Nakamura, Y., Honda, T., Furukawa, K., Urano, T., Wiels, J., Uchikawa, M., Ozaki, N., Matsuo, S., Sugiura, Y., and Furukawa, K.: Murine glycosyltransferases responsible for the expression of globo-series glycolipids: cDNA structures, mRNA expression, and distribution of their products. Glycobiology 15, 1257-67, 2005
Koga, M., Gilbert, M., Li, J., Koike, S., Takahashi, M., Furukawa, K., Hirata, K., Yuki, N.: Antecedent infections in Fisher syndrome: a common pathogenesis of molecular mimicry. Neurology 64, 1605-1611, 2005
Kato, H., Goto, D.B., Martienssen, R.A., Urano, T., Furukawa. K., and Murakami, Y.: RNA polymerase II is required for siRNA generation and peri-centromeric heterochromatin formation in fission yeast. Science 309, 467-469, 2005
Handa, Y., Ozaki, N., Honda, T., Furukawa, K., Tomita, Y., Inoue, M., Okada, M., Furukawa, K., and Sugiura, Y.: GD3 synthase gene knockout mice exhibit thermal hyperalgesia and mechanical allodynia but decreased response to formalin induced prolonged noxious stimulation. Pain 117, 271-279, 2005
Zhao, W., Soejima, H., Higashimoto, K., Nakagawachi, T., Urano, T., Kudo, S., Matsukura, S., Matsuo, S., Joh, K. and Mukai, T.: The essential role of histone H3 Lys9 di-methylation and MeCP2 binding in MGMT silencing with poor DNA methylation of the promoter CpG island. J. Biochem. (Tokyo). 137, 431-440, 2005
Hayashida, Y., Goi, T., Hirono, Y., Katayama, K., Urano, T. and Yamaguchi, A.: PPP1R3 gene (protein phosphatase 1) alterations in colorectal cancer and its relationship to metastasis. Oncol. Rep. 13, 1223-1227, 2005
Matsuura, T., Shimono, Y., Kawai, K., Murakami, H., Urano, T., Niwa, Y., Goto, H. and Takahashi, M.: PIAS proteins are involved in the SUMO-1 modification, intracellular translocation and transcriptional repressive activity of RET finger protein. Exp. Cell Res. 308, 65-77, 2005
Kanoh, J., Sadaie, M., Urano, T. and Ishikawa, F.: Telomere-binding protein Taz1 establishes Swi6 heterochromatin independently of RNAi at telomeres. Curr. Biol., 15, 1808-1819, 2005
Nguyen, H.G., Chinnappan, D., Urano, T. and Ravid, K.: Mechanism of Aurora-B degradation and its dependency on intact KEN and A-boxes: identification of an aneuploidy-promoting property. Mol. Cell Biol. 25, 4977-4992, 2005
Katagiri, C., Masuda, K., Urano, T., Yamashita, K., Araki, Y., Kikuchi, K. and Shima, H.: Phosphorylation of Ser-446 determines stability of MKP-7. J Biol Chem. 280, 14716-14722, 2005

大学院入学案内

ポストゲノム研究の重要な柱の一つとして、タンパク質や脂質に結合する糖鎖の意義の解明が生物学の重要課題となっています。また、癌や神経変性症などの難病の克服の上でも、複合糖質の糖鎖の役割を明らかにすることが必須の課題となっています。
このような時期に、文部科学省の特定領域研究「糖鎖によるタンパク質と分子複合体の機能解析」(略称:グライコミクス)(領域代表:古川鋼一)が14年度~18年度の5年間のプロジェクトとして展開されました。当研究室はその先頭に立って、糖鎖生物学研究を推進してきました。また、細胞増殖・分裂の制御機構の研究は、個々の遺伝子機能の解析から、染色体全体の分裂機構の解明に多くの研究者の関心が向いている中で、当研究室はその牽引者として研究をリードしようとしています。
飛躍的に進展しつつある分子生物学とゲノム医学の成果を生かしながら、糖鎖の分子機能の解明とその臨床応用の研究に積極的に参加せんとする、若々しい学生の入学を期待しています。医科学修士課程、博士課程(医学系研究科)があり、前者は4年生大学の卒業者、後者は、医学部、歯学部、獣医学部の卒業者、または修士課程の卒業者を対象にしています。

指導方針と体制
修士および博士課程の1~2年目においては、生化学、分子生物学の基本手技と原理を徹底的に修得すると共に、論文を読みこなし批判できるための基礎訓練を行います。その間に各々のポテンシャルに合致した課題に取り組み、高学年ではよりレベルの高い研究を成し遂げられるようサポートします。また、国内外の学会、シンポジウム等に積極的に参加して発表能力の向上をはかると共に、全体のレベルアップに反映させます。さらに国内外のグループとの協同研究を推進し、中途の留学、卒業後の留学などを積極的に支援していきます。