Protease-mediated regulation of host immune system and application as therapeutic targets

• Project/Area Number: 19209058
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Kyushu University
• Principal Investigator: YAMAMOTO Kenji Kyushu University, 大学院・薬学研究院, 特任教授 (40091326)
• Co-Investigator(Kenkyū-buntansha): TSUKUBA Takayuki 長崎大学, 大学院・医歯薬学総合研究科, 教授 (30264055) ; TAKII Ryosuke 山口大学, 大学院・医学研究科, 助教 (00419558) ; KADOWAKI Tomoko 長崎大学, 大学院・医歯薬学総合研究科, 助教 (70336080) ; KAWAKUBO Tomoyo 九州大学, 大学院・薬学研究院, 特任助教 (70507813)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥50,050,000 (Direct Cost: ¥38,500,000、Indirect Cost: ¥11,550,000); Fiscal Year 2009: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000); Fiscal Year 2008: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2007: ¥24,050,000 (Direct Cost: ¥18,500,000、Indirect Cost: ¥5,550,000)
• Keywords: 歯学 / 蛋白質 / トランスレーショナルリサーチ / 発現制御 / 薬理学 / 癌 / 免疫学 / プロテアーゼ

Research Abstract

In this study, we investigated the nature and function of both host-and bacteria-derived proteases in host immune system. Cathepsin E (catE) and gingipains were treated as a host-derived endolysosomal protease and bacterial proteases, respectively. The obtained results are as follows : (i) CatE differentially regulated the nature and function of dendritic cells and macrophages, (ii) CatE deficiency caused impairment of autophagy in macrophages manifesting mitochondria dysfunction and enhanced oxidative stress, (iii) Endogenous Cat E expression levels were positively associated with the growth arrest and metastasis reduction of tumor cells in vivo and the concomitant increase of tumor-associated activated macrophages in tumor microenvironment, (iv) CatE specifically induced apoptosis in tumor cells without affecting normal cells in vitro by catalyzing the proteolytic release of soluble TRAIL from tumor cell surface, (v) Peptide-aptamer-based inhibitors and activators of CatE was generated by cDNA display techniques, (vi) Atherosclerosis progression in apolipoprotein E-knockout mice was accelerated by P. gingivalis infection, which was mediated by selective proteolysis of apolipoprotein B-100 by Arg-gingipain (Rgp), (vii) A risk for preterm birth and fetal death in pregnant mice was enhanced by P. gingivalis infection and inhibited by combination treatment of Rgp and Kgp inhibitors, (iii) A newly developed peptide analogue inhibiting both Rgp and Kgp suppressed most of the pethogenicity of P. gingivalis.

Research Products

• [Journal Article] Cathepsin E enhances anticancer activity of doxorubicin on human prostate cancer cells showing resistance to TRAIL-mediated apoptosis. (2010)
  • Author(s): Yasukochi A, Kawakubo T, Nakamura S, Yamamoto K.
  • Journal Title: Biol Chem (in press)
  • NAID: 120006900038
  • Peer Reviewed
• [Journal Article] Cathepsin E enhances anticancer activity of doxorubicin on human prostate cancer cells showing resistance to TRAIL-mediated apoptosis (2010)
  • Author(s): Yasukochi, A., et al.,
  • Journal Title: Biol Chem (In press)
  • NAID: 120006900038
  • Peer Reviewed
• [Journal Article] Impaired chemotaxis and cell adhesion due to decrease in wide range of cell surface receptors in cathepsin E-deficient macrophages. (2009)
  • Author(s): Tsukuba T, Yanagawa M, Okamoto K, Okamoto Y, Yasuda Y, Nakayama KI, Kadowaki T, Yamamoto K.
  • Journal Title: J. Biochem. 145(5) Pages: 565-573
  • Peer Reviewed
• [Journal Article] Development of systemin in vitro evolution and its application to generation of peptide aptamer-based inhibitors of cathepsin E. (2009)
  • Author(s): Kitamura K, Yoshida C, Kinoshita Y, Kadowaki T, Takahashi Y, Tayama T, Kawakubo T, Naimuddin M, Salimulla M, Nemoto N, Hanada K, Husimi Y, Yamamoto K, Nishigaki K.
  • Journal Title: J. Mol. Biol. 387 Pages: 1186-1198
  • Peer Reviewed
• [Journal Article] Impaired chemotaxis and cell adhesion due to decrease in wide range of cell surface receptors in cathepsin E-deficient macrophages. (2009)
  • Author(s): Tsukuba, T,, et al.
  • Journal Title: J. Biochem. 145 Pages: 565-573
  • Peer Reviewed
• [Journal Article] Development of systemin in vitro evolution and its application to generation of peptide aptamer-based inhibitors of cathepsin E. (2009)
  • Author(s): Kitamura, K,, et al.
  • Journal Title: J. Mol. Biol. 387 Pages: 1186-1198
  • Peer Reviewed
• [Journal Article] Development of systemin in vitro evolution and its application to generation of peptide aptamer-based inhibitors of cathepsin E (2009)
  • Author(s): Kitamura K, et al.
  • Journal Title: Journal of Molecular Biology 387 Pages: 1186-1198
  • Peer Reviewed
• [Journal Article] Impaired chemotaxis and cell adhesion due to decrease in wide range of cell surface receptors in cathepsin E-deficient macrophages (2009)
  • Author(s): Tsukuba T, et al.
  • Journal Title: Journal of Biochemistry 145(In press)
  • Peer Reviewed
• [Journal Article] Association of cathepsin E deficiency with the increased territorial aggressive response of mouse (2008)
  • Author(s): Shigematsu N., Fukuda T., Yamamoto T., Nishioku T., Yamaguchi T., Himeno M., Nakayama K.I., Tsukuba T., Kadowaki T., Okamoto K., Higuchi S., Yamamoto K.
  • Journal Title: J. Neurochem. 105 Pages: 1394-1404
  • Peer Reviewed
• [Journal Article] Determination of active site of Lysine-specific cysteine proteinase (Lys-gingipain) by use of a Porphyromonas gingivalis plasmid system. (2008)
  • Author(s): Ishida Y., Hu J.P., Sakai E., Kadowaki T., Yamamoto K., Tsukuba T., Nakayama K., Okamoto K.
  • Journal Title: Arch. Oral Biol. 53(6) Pages: 538-544
  • NAID: 120006984583
  • Peer Reviewed
• [Journal Article] An immunohistochemical study on a unique colocalization relationship between substance P and GABA in the central nucleus of amygdala. (2008)
  • Author(s): Shigematsu, N., Yamamoto, K., Higuchi, S., Fukuda, T.
  • Journal Title: Brain Res. 1198 Pages: 55-67
  • Peer Reviewed
• [Journal Article] Gene expression of profiling of mammary glands of cathepsin E-deficient mice compared with wild-type littermates. (2008)
  • Author(s): Kawakubo T., Yasukochi A., Tsukuba T., Kadowaki T., Yamamoto K.
  • Journal Title: Biochimie 90 Pages: 396-404
  • NAID: 120006900027
  • Peer Reviewed
• [Journal Article] Association of cathepsin E deficiency with the increased territorial aggressive response of mouse. (2008)
  • Author(s): Shigematsu N., et al.
  • Journal Title: Journal of Neurochemistry 105 Pages: 1394-1404
  • Peer Reviewed
• [Journal Article] Determination of active site of Lysine-specific cysteine proteinase (Lys-gigipain) by use of a Porphyromonas gingivalis plasmid system (2008)
  • Author(s): Ishida Y., et al.
  • Journal Title: Archives Oral Biology 53 Pages: 538-544
  • Peer Reviewed
• [Journal Article] An immunohistochemical study on a unique colocalization relationship between substance P and GABA in the central nucleus of amygdala (2008)
  • Author(s): Shigematsu, N, et al.
  • Journal Title: Brain Research 1198 Pages: 55-67
  • Peer Reviewed
• [Journal Article] Gene expression of profiling of mammary glands of cathepsin E-deficientmice compared with wild-type littermates (2008)
  • Author(s): Kawakubo T, et al.
  • Journal Title: Biochimie 90 Pages: 396-404
  • Peer Reviewed
• [Journal Article] Cathepsin E Prevents Tumor Growth and Metastasis by Catalyzing the Proteolytic Release of Soluble TRAIL from Tumor Cell (2007)
  • Author(s): Kawakubo T., Okamoto K., Iwata J., Shin M., Okamoto Y., Yasukochi A., Nakayama K.I., Kadowaki T., Tsukuba T., Yamamoto K.
  • Journal Title: Surface. Cancer Res. 67 Pages: 10869-10878
  • Peer Reviewed
• [Journal Article] Differential regulation of the nature and functions of dendritic cells and macrophages by cathepsin E. (2007)
  • Author(s): Kakehashi H., Nishioku T., Tsukuba T., Kadowaki T., Nakamura S., Yamamoto K.
  • Journal Title: J. Immunol. 179 Pages: 5728-5737
  • Peer Reviewed
• [Journal Article] Squamous cell carcinoma antigen 1 is an inhibitor of parasite-derived cysteine proteases. (2007)
  • Author(s): Kanaji, S., Tanaka, Y., Sakata, Y., Takeshita, K., Arima, K., Ohta, S., Hansell, E.J., Caffrey, C., Mottram, J.C., Lowther, J., Donnelly, S., Stack, C., Kadowaki, T., Yamamoto, K., McKerrow, J.H., Dalton, J.P., Coombs, G.H., Izuhara, K.
  • Journal Title: FEBS Lett. 581 Pages: 4260-4264
  • Peer Reviewed
• [Journal Article] Construction of recombinant hemagglutinin derived from the gingipain-encoding gene of Porphyromonas gingivalis, identification of its target protein on erthrocytes, and inhibition of hemaggelutination by an interdomain regional peptide. (2007)
  • Author(s): Sakai, E., Naito, M., Sato, K., Hotokezaka, H., Kadowaki, T., Kamaguch, A., Yamamoto, K., Okamoto, K., Nakayama, K.
  • Journal Title: J. Bacteriol. 189 Pages: 3977-3986
  • Peer Reviewed
• [Journal Article] Cathepsin E deficiency induces a novel form of lysosomal storage disorder 5 showing the accumulation of lysosomal membrane sialoglycoproteins and the elevation of lysosomal pH in macrophages. (2007)
  • Author(s): Yanagawa, M., Tsukuba, T., Nishioku, T., Okamoto, Y., Okamoto, K., Takii, R., Terada, Y., Nakayama, K.T., Kadowaki, T., Yamamoto, K
  • Journal Title: J. Biol. Chem. 282 Pages: 1851-1862
  • Peer Reviewed
• [Journal Article] Association of cathepsin E with tumor growth arrest through angiogenesis inhibition and enhanced immune responses. (2007)
  • Author(s): Shin, M., Kadowaki, T., Iwata, J., Kawakubo, T., Yamaguchi, N., Takii, R., Tsukuba, T., Yamamoto, K.
  • Journal Title: Biol. Chem. 388 Pages: 1173-1181
  • NAID: 120006900037
  • Peer Reviewed
• [Journal Article] A role for gingipains in cellular responses and bacterial survival in Porphyromonas gingicalis-infected cells. (2007)
  • Author(s): Kadowaki, T., Takii, R., Yamatake, K., Kawakubo, T., Tsukuba, T., Yamamoto, K.
  • Journal Title: Frontiers in Biosci. 12 Pages: 4800-4809
  • Peer Reviewed
• [Journal Article] Role for gingipains in Porphyromonas gingivalis traffic to phagolysosomes and survival in human aortic endothelilal cells. (2007)
  • Author(s): Yamatake, K., Maeda, M., Kadowaki, T., Takii, R., Tsukuba, T., Ueno, T., Kominami, E., Yokota, S., Yamamoto, K.
  • Journal Title: Infect. Immun. 75 Pages: 2090-2100
  • Peer Reviewed
• [Journal Article] Selection-by-function: effifient enrichment of cathepsin E inhibitors from a DNA library. (2007)
  • Author(s): Naimuddin, M., Kitamura, K., Kinoshita, Y., Honda-Takehashi, Y., Murakami, M., Ito, M., Yamamoto, K., Hanada, K., Husimi, Y., Nishigaki, K.
  • Journal Title: J. Mol. Recognit. 20 Pages: 58-68
  • Peer Reviewed
• [Journal Article] Differential Regulation of the Narure and Functions of Dendritic Cells and Macrophages by Cathepshin E. (2007)
  • Author(s): Kakehashi, H., et. al.
  • Journal Title: The Journal of Immunology 179 Pages: 5728-5737
  • Peer Reviewed
• [Journal Article] Cathepsin E Prevents Tumor Growth and Metastasis by Catalyzing the Proteohnic Release of Soluble TRAIL from Tumor Cell Surface. (2007)
  • Author(s): Kawakubo, T., et. al.
  • Journal Title: Cancer Research 67 Pages: 10869-10878
  • Peer Reviewed
• [Journal Article] Squamous cell carcinoma anligen 1 is an inhibitor of parasite-derived cysteine proteases. (2007)
  • Author(s): Kanaji, S., et. al.
  • Journal Title: FEBS Letter 581 Pages: 4260-4264
  • Peer Reviewed
• [Journal Article] Constnlction of recombinant hemagglutinin derived from the gingipain-encoding gene of Porphyromonas gingivalis, identification of its target protein on erthrocytes, and inhibition of hemaggelutination by an interdomain regional peptide. (2007)
  • Author(s): Sakai, E., et. al.
  • Journal Title: Journal Bacteriology 189 Pages: 3977-3986
  • Peer Reviewed
• [Journal Article] Association of cathepsin E with tumor growth arrest through angiogenesis inhibition and enhanced innune responses. (2007)
  • Author(s): Shin, M., et. al.
  • Journal Title: Biological Chemistry 388 Pages: 1173-1181
  • Peer Reviewed
• [Journal Article] A role for gingipains in cellular responses and bacterial survival in Porphyromon as gingicalis-infected cells. (2007)
  • Author(s): Kadowaki, T., et. al.
  • Journal Title: Frontiers in Bioscience 12 Pages: 4800-4809
  • Peer Reviewed
• [Journal Article] Role for gingipains in Porphyromonas gingivalis traffic to phagolysosomes and survival in human aortic endothelilal cells. (2007)
  • Author(s): Yamatake, K., et. al.
  • Journal Title: Infection and Immunity 75 Pages: 2090-2100
  • Peer Reviewed
• [Journal Article] Selection-by-function:effifient enrichment of cathepsin E inhibitors from a DNA library. (2007)
  • Author(s): Naimuddin, M., et. al.
  • Journal Title: Journal Molecular Recognition 20 Pages: 58-68
  • Peer Reviewed
• [Journal Article] Cathepsin E deficiency induces a novel form of lysosomal storage disorder showing the accumulation of lysosomal membrane sialoglycoproteins and the elevation of lysosomal pH in macrophages. (2007)
  • Author(s): Yanagawa, M., et. al.
  • Journal Title: Journal of Biological Chemistry 282 Pages: 1851-1862
  • Peer Reviewed
• [Presentation] Transcription factor Spl regulates the expression of the murine cathepsin E gene in gastric adenosarcoma cells (2010)
  • Author(s): 岡元邦彰, 他
  • Organizer: 第63回日本薬理学会年会
  • Place of Presentation: 大阪
• [Presentation] カテブシンE欠損によるオートファジー低下とそれに伴うミトコンドリア機能低下と酸化ストレスの増大 (2009)
  • Author(s): 筑波隆幸, 他
  • Organizer: 第14回日本病態プロテアーゼ学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-08-21
• [Presentation] ペプチドペア法によるカテプシンE活性調節ペプチドの高機能化 (2009)
  • Author(s): 北村幸一郎, 他
  • Organizer: 第14回日本病態プロテアーゼ学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-08-21
• [Presentation] 反復流産患者の妊娠初期におけるCathepsin Eの存在と意義 (2009)
  • Author(s): 尾崎康彦, 他
  • Organizer: 第14回日本病態プロテアーゼ学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-08-21
• [Presentation] Impairment of autophagy accompanied by increased aberrant mitochondria and oxidative stress in cathepsin E-deficient macrophages (2009)
  • Author(s): Tsukuba T., et al.
  • Organizer: 第5回オートファジーに関する国際会議
  • Place of Presentation: 滋賀
• [Presentation] Combination of cathepsin E and the anticancer drug doxorubicin for enhanced cytotoxicity of human prostate carcinoma cells (2009)
  • Author(s): Yasukochi, A., et al.
  • Organizer: 6^<Th> General Meeting of the International Proteolysis Society
  • Place of Presentation: Australia
• [Presentation] Association of cathepsin E deficiency with transition from normal development to neoplastic lesions in mammary glands (2009)
  • Author(s): Kawakubo, T., et al.
  • Organizer: 6^<Th> General Meeting of the International Proteolysis Society
  • Place of Presentation: Australia
• [Presentation] カテプシンE欠損はオートファジーの低下とそれに伴うミトコンドリア機能異常と酸化ストレスを引き起こす (2008)
  • Author(s): 筑波隆幸, 他
  • Organizer: 日本分子生物学会・日本生化学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] マウスカテプシンE遺伝子発現に関与する転写因子Sp1 (2008)
  • Author(s): 岡本美子, 他
  • Organizer: 日本分子生物学会・日本生化学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] 高速分子進化技術eRAPANSY : 未来型創薬ツール (2008)
  • Author(s): 西垣功一, 他
  • Organizer: 日本分子生物学会・日本生化学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] Identification of cathepsin E target genes in mouse mammary gland (2008)
  • Author(s): Kawakubo T, et al.
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-30
• [Presentation] Sensitization for anti-cancer drug-induced apoptosis by cathepsin E (2008)
  • Author(s): Yasukochi A, et al.
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-30
• [Presentation] カテプシンE欠損マウスにおける高脂血症および脂肪肝の誘導 (2008)
  • Author(s): 門脇知子, 他
  • Organizer: 歯科基礎医学会
  • Place of Presentation: 東京
  • Year and Date: 2008-09-23
• [Presentation] カテプシンE遺伝子発現に関与する転写因子Sp1 (2008)
  • Author(s): 岡元邦彰, 他
  • Organizer: 歯科基礎医学会
  • Place of Presentation: 東京
  • Year and Date: 2008-09-23
• [Presentation] カテプシンEによるTRAIL誘導性アポトーシスと感受性調節機構 (2008)
  • Author(s): 川久保友世, 他
  • Organizer: 歯科基礎医学会
  • Place of Presentation: 東京
  • Year and Date: 2008-09-23
• [Presentation] カテプシンE欠損による遊走能および細胞接着能の低下 (2008)
  • Author(s): 筑波隆幸, 他
  • Organizer: 歯科基礎医学会
  • Place of Presentation: 東京
  • Year and Date: 2008-09-23
• [Presentation] Cathepsin E in tumor progression and bacterial infection (2008)
  • Author(s): Yamamoto K, et al.
  • Organizer: 11^<th> International Symposium on Proteinase Inhibitors and Biological Control
  • Place of Presentation: Slovenia
  • Year and Date: 2008-08-31
• [Presentation] Comparative genomic profiling of mouse mammary glands using DNA Microarrays : Identification of cathepsin E-target genes (2008)
  • Author(s): Kawakubo T, et al.
  • Organizer: 11^<th> International Symposium on Proteinase Inhibitors and Biological Control
  • Place of Presentation: Slovenia
  • Year and Date: 2008-08-31
• [Presentation] Sensitization for anti-tumor drug-induced apoptosis in tumor cells by cathepsin E (2008)
  • Author(s): Yasukochi A, et al.
  • Organizer: 11^<th> International Symposium on Proteinase Inhibitors and Biological Control
  • Place of Presentation: Slovenia
  • Year and Date: 2008-08-31
• [Presentation] カテプシンEの機能と疾患および治療を目指して (2008)
  • Author(s): 山本健二
  • Organizer: 日本病態プロテアーゼ学会
  • Place of Presentation: 大阪
  • Year and Date: 2008-08-23
• [Presentation] カテプシンEと抗腫瘍剤の併用による抗腫瘍効果の増強作用 (2008)
  • Author(s): 安河内篤, 他
  • Organizer: 日本病態プロテアーゼ学会
  • Place of Presentation: 大阪
  • Year and Date: 2008-08-23
• [Presentation] Identification of differentially expressed markers in cathepsin E-deficient mouse mammary gland (2008)
  • Author(s): Kawakubo T, et al.
  • Organizer: 日本細胞生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2008-06-29
• [Presentation] Effect of doxorubicin on cathepsin E-mediated tumor cell apoptosis (2008)
  • Author(s): Yasukochi A, et al.
  • Organizer: 日本細胞生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2008-06-29
• [Presentation] カテプシンE欠損はマクロファージの膜蛋白質輸送異常とミトコンドリア機能異常を起こす (2007)
  • Author(s): 筑波 隆幸, 他
  • Organizer: 第30回日本分子生物学会・第80回日本生化学会合同大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-12-13
• [Presentation] 血管新生抑制と生体防御増強によるカテプシンEの腫瘍抑制 (2007)
  • Author(s): 進 正史, 他
  • Organizer: 第60回日本薬理学会西南部会
  • Place of Presentation: 宮崎
  • Year and Date: 2007-11-22
• [Presentation] Roles for gingipains in atherosclerosis progression accelerated by bacterial exposure (2007)
  • Author(s): 門脇 知子, 他
  • Organizer: 5^<th> General Meeting of the Intemational Proteolysis Society
  • Place of Presentation: ギリシア
  • Year and Date: 2007-10-23
• [Presentation] Control of the endosome/lysosome system of macrophages by cathepsin E (2007)
  • Author(s): 筑波 隆幸, 他
  • Organizer: 5^<th> General Meeting of the International Proteolysis Society
  • Place of Presentation: ギリシア
  • Year and Date: 2007-10-22
• [Presentation] Association of cathepsin E with host defense against tumor cells (2007)
  • Author(s): 川久保 友世, 他
  • Organizer: 5^<th> General Meeting of the International Proteolysis Society
  • Place of Presentation: ギリシア
  • Year and Date: 2007-10-21
• [Presentation] A possible link between Porpphyromonas gingivalis infection and preterm delivery and low birth weight (2007)
  • Author(s): 瀧井 良祐, 他
  • Organizer: 5^<th> General Meeting of the International Proteolysis Society
  • Place of Presentation: ギリシア
  • Year and Date: 2007-10-21
• [Presentation] A new strategy for combinational cancer therapy using cathepsin E (2007)
  • Author(s): 安河内 篤, 他
  • Organizer: 5^<th> General Meeting of the International Proteolvsis Society
  • Place of Presentation: ギリシア
  • Year and Date: 2007-10-21
• [Presentation] Cathepsin E-mediated immunological surveillance on tumor (2007)
  • Author(s): 川久保 友世, 他
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-03
• [Presentation] Increased susceptibility of tumor cells to anti-tumor drugs by cathepsin E (2007)
  • Author(s): 安河 内篤, 他
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: バシフィコ横浜
  • Year and Date: 2007-10-03
• [Presentation] カテプシンE欠損によるミトコンドリア機能異常と酸化ストレス亢進 (2007)
  • Author(s): 筑波 隆幸, 他
  • Organizer: 第49回歯科基礎医学会
  • Place of Presentation: 北海道大学
  • Year and Date: 2007-08-30
• [Presentation] P.gingivalis感染とインスリン抵抗性に関する実験的解析 (2007)
  • Author(s): 門脇 知子, 他
  • Organizer: 第49回歯科基礎医学会
  • Place of Presentation: 北海道大学
  • Year and Date: 2007-08-30
• [Presentation] 赤血球におけるカテプシンEの役割 (2007)
  • Author(s): 岡元 邦彰, 他
  • Organizer: 第49回歯科基礎医学会
  • Place of Presentation: 北海道大学
  • Year and Date: 2007-08-30
• [Presentation] 腫瘍免疫におけるカテプシンEの役割 (2007)
  • Author(s): 川久保 友世, 他
  • Organizer: 第49回歯科基礎医学会
  • Place of Presentation: 北海道大学
  • Year and Date: 2007-08-29
• [Presentation] 歯周病原菌P. orphyromonas gingivalisが引き起こす早産・低体重児出産の解析 (2007)
  • Author(s): 瀧井 良祐, 他
  • Organizer: 第49回歯科基礎医学会
  • Place of Presentation: 北海道大学
  • Year and Date: 2007-08-29
• [Presentation] 歯周病原因菌Porphyromonas gingivalisと早産・低体重児出産に関する基礎的研究 (2007)
  • Author(s): 瀧井 良祐
  • Organizer: 第12回病態と治療に関するプロテアーゼとインヒビター学会
  • Place of Presentation: 大阪千里ライフサイエンスセンター
  • Year and Date: 2007-08-03
• [Presentation] Cathepsin E differentially regulates the nature and functions of macrop hages and dendritic cells (2007)
  • Author(s): 山本 健二, 他
  • Organizer: Xthe International Symposium on Protsinase Inhibitors and Biological Control
  • Place of Presentation: スロベニア
  • Year and Date: 2007-07-23
• [Presentation] Cathepsin E exerts tumoricidal activity through generation of TRAIL From the tumor cell surface (2007)
  • Author(s): 川久保 友世, 他
  • Organizer: 第59回日本細胞生物学会大会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2007-05-28
• [Presentation] 皮膚バリア機能および免疫応答におけるカテプシンEの役割 (2007)
  • Author(s): 大日 輝記, 他
  • Organizer: 日本皮膚科学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-04-20
• [Patent(Industrial Property Rights)] 新規ペプチド及びその使用 (2010)
  • Inventor(s): 西垣功一、北村幸一郎、Madhu Biyani、二上雅恵、山本健二、川久保友世、安河内篤
  • Industrial Property Rights Holder: 西垣功一、北村幸一郎、Madhu Biyani、二上雅恵、山本健二、川久保友世、安河内篤
  • Industrial Property Number: 2009-245763
  • Filing Date: 2010-03-17
  • Acquisition Date: 2010-03-17
• [Patent(Industrial Property Rights)] カテプシンEの腫瘍マーカーとしての用途及びカテプシンEならびにカテプシンDの腫瘍血管新生阻害療法のターゲットとしての用途 (2010)
  • Inventor(s): 山本健二、岩田淳一
  • Industrial Property Rights Holder: 山本健二、岩田淳一
  • Filing Date: 2010-02-12
  • Acquisition Date: 2010-02-12
• [Patent(Industrial Property Rights)] アンチエイジング剤 (2009)
  • Inventor(s): 山本健二、川久保友世、安河内篤
  • Industrial Property Rights Holder: 山本健二、川久保友世、安河内篤
  • Industrial Property Number: 2009-264894
  • Filing Date: 2009-11-20
  • Acquisition Date: 2009-11-20
• [Patent(Industrial Property Rights)] 新規な抗癌カテプシン製剤およびそれを用いた癌併用療法抗癌剤 (2007)
  • Inventor(s): 山本健二、川久保友世、安河内篤
  • Industrial Property Rights Holder: 山本健二、川久保友世、安河内篤
  • Industrial Property Number: 2008-500586
  • Filing Date: 2007-02-19
  • Acquisition Date: 2007-02-19