坂本 直哉

坂本 直哉

教授

略歴

昭和56年3月
栃木県立宇都宮高等学校卒業
昭和62年3月
東京医科歯科大学医学部医学科卒業
昭和62年4月
東京医科歯科大学第二内科
昭和63年6月
横須賀共済病院内科
平成1年6月
土浦協同病院内科
平成6年2月
米国コネチカット州立大学医学部リサーチフェロー
平成13年4月
東京医科歯科大学消化器内科助手
平成18年4月
同、分子肝炎制御学講座准教授
平成24年3月
北海道大学医学研究科内科学講座消化器内科学分野教授

専門領域

消化器肝臓病学、臨床ウイルス学

所属学会等

  • 日本内科学会認定医・総合内科専門医・指導医
  • 日本肝臓病学会指導医・学会評議員
  • 日本消化器病学会認定専門医・学会評議員
  • 日本消化器内視鏡学会指導医
  • 日本肝癌研究会
  • 日本肝がん分子標的治療研究会
  • Member of the American Association for the Study of Liver Diseases
  • Member of the American Association of Microbiology
  • 東京医科歯科大学医学部非常勤講師
  • 山梨大学医学部非常勤講師

雑誌編集委員

  • Journal of Gastroenterology associate editor
  • Journal of Gastroenterology and Hepatology editorial board
  • 「肝胆膵」編集委員

省庁関係

  • 厚生労働省 肝炎等克服緊急対策研究事業「肝炎ウイルス感染複製増殖過程の解明と新規治療法開発に関する研究(脇田班)」
  • 厚生労働省 肝炎等克服緊急対策研究事業「C型肝炎難治症例の病態解明と抗ウイルス治療に関する研究(竹原班)」
  • 厚生労働省 肝炎等克服緊急対策研究事業「ウイルス性肝炎に対する応答性を規定する宿主因子も含めた情報のデータベース構築・治療応用に関する研究(田中班)」
  • 厚生労働省 肝炎等克服緊急対策研究事業「薬剤耐性肝炎ウイルス感染の病態解明と対策に関する研究(榎本班)」
  • 日本学術振興会特別研究員審査会専門委員

受賞歴

昭和56年3月
栃木県立宇都宮高等学校卒業
平成14年
第9回国際科学振興財団フォーラム研究奨励賞
平成15年
第5回肝病態・治療研究会研究奨励賞
平成16年
ウイルス肝炎研究財団研究奨励賞
平成16年
日本肝臓学会・冠アワード
平成17年
日本消化器病学会研究助成
平成17年
第12回国際科学振興財団フォーラム研究奨励賞
平成17年
Liver Forum Kyoto研究奨励賞
平成18年
宮川庚子研究財団研究助成
平成23年
日本肝臓学会研究奨励賞

業績

  1. Sakurai F, Furukawa N, Higuchi M, Okamoto S, Ono K, Yoshida T, Kondoh M, Yagi K, Sakamoto N, Katayama K, Mizuguchi H: Suppression of hepatitis C virus replicon by adenovirus vector-mediated expression of tough decoy RNA against miR-122a. Virus Research 2012; in press.
  2. Nakagawa M, Sakamoto N, Watanabe T, Nishimura-Sakurai Y, Onozuka Y, Azuma S, Kakinuma S, Nitta S, Kiyohashi K, Kusano-Kitazume A, Murakawa M, Yoshino K, Itsui Y, Tanaka Y, Mizokami M, Watanabe M, Ochanomizu Liver Conference Study Group: Association of ITPA gene variant and serum ribavirin concentration with blood cells decline in pegylated interferon-alfa plus ribavirin therapy for chronic hepatitis C. Hepatol Int 2012; in press.
  3. Cheng J-C, Yeh YJ, Tseng CP, Hsu SD, Chang YL, Sakamoto N, Huang HD: Let-7b is a novel regulator of hepatitis C virus replication. Cell Mol Life Sci 2012; EPub ahead of Print.
  4. Nichols DB, Fournet G, Gurukumar KR, Basu A, Lee JC, Sakamoto N, Kozielski F, Musmuca I, Joseph B, Ragno R, Kaushik-Basu N: Inhibition of hepatitis C virus NS5B polymerase by S-trityl-L-cysteine derivatives. Eur J Med Chem 2012; EPub ahead of Print.
  5. Kurosaki M, Hiramatsu N, Sakamoto M, Suzuki Y, iwasaki M, Tamori A, Matsuura K, Kakinuma S, Sugauchi F, Sakamoto N, Nakagawa M, Izumi N: Data Mining Analysis of Hepatocellular Carcinoma Risk Predictors in Chronic Hepatitis C. J Hepatol 2011; EPub ahead of Print
  6. Kusano-Kitazume A, Sakamoto N, Okuno Y, Sekine-Osajima Y, Nakagawa M, Kakinuma S, Kiyonashi K, Nitta S, Murakawa M, Azuma S, Nishimura-Sakurai Y, Hagiwara M, Watanabe M: Identification of novel N-(morpholine-4-carbonyloxy) amidine compounds as potent inhibitors against hepatitis C virus replication. Antimicrob Agent Chemother; 2012; 56(3):1315-1323.
  7. Kurosaki M, Hiramatsu N, Sakamoto M, Suzuki Y, Iwasaki M, Tamori A, Matsuura K, Kakinuma S, Sugauchi F, Sakamoto N, Nakagawa M, Yatsuhashi H, Izumi N: Age and total ribavirin dose is an independent predictor of relapse among early virological responders to peg-interferon plus ribavirin therapy in chronic hepatitis C revealed by data mining analysis. Antivir Ther 2011; 17:35-43.
  8. Asahina Y, Tsuchiya K, Muraoka M, Tanaka K, Suzuki Y, Tamaki N, Hoshioka Y, Yasui Y, Katoh T, Hosokawa T, Ueda K, Nakanishi H, Itakura J, Takahashi Y, Kurosaki M, Enomoto N, Nitta S, Sakamoto N, Izumi N: Association of gene expression involving innate immunity and genetic variation in IL28B with antiviral response. Hepatology 2011; 55(1):20-29.
  9. Kadokura M, Maekawa S, Sueki R, Miura M, Komase K, Shindo H, Amemiya F, Uetake T, Inoue T, Sakamoto M, Nakagawa M, Sakamoto N, Watanabe M, Enomoto N. Analysis of the complete open reading frame of hepatitis C virus in genotype 2a infection reveals critical sites influencing the response to peginterferon and ribavirin therapy. Hepatol Int 2011; 5(3):789-799.
  10. Yoshida T, Takayama K, Kondoh M, Sakurai F, Tani H, Sakamoto N, Matsuura Y, Mizuguchi H, Yagi K: Use of human hepatocyte-like cells derived from induced pluripotent stem cells as a model for hepatocytes in hepatitis C virus infection. Biochem Biophys Res Commun 2011; 416(1-2):119-124.
  11. Takaya D, Yamashita A, Kamijo K, Gomi J, Ito M, Maekawa S, Enomoto N, Sakamoto N, Watanabe Y, Arai R, Umeyama H, Honma T, Matsumoto T, Yokoyama S: A new method for induced fit docking (GENIUS) and its application to virtual screening of novel HCV NS3-4A protease inhibitors, Bioorganic Medicinal Chemistry 2011; 19(22):6892-6905.
  12. Zheng X, Tsuchiya K, Okamoto R, Iwasaki M, Kano Y, Sakamoto N, Nakamura T, Watanabe M. Suppression of hath1 gene expression directly regulated by hes1 via notch signaling is associated with goblet cell depletion in ulcerative colitis. Inflamm Bowel Dis 2011;17(11):2251-2260.
  13. Ueyama M, Nakagawa M, Sakamoto N, Onozuka I, Funaoka Y, Watanabe T, Nitta S, et al. Serum interleukin-6 levels correlate with resistance to treatment of chronic hepatitis C infection with pegylated-interferon-alpha2b plus ribavirin. Antivir Ther 2011;16:1081-1091.
  14. Tanaka Y, Kurosaki M, Nishida N, Sugiyama M, Matsuura K, Sakamoto N, Enomoto N, Yatsuhashi H, Nishiguchi S, Hino K, Hige S, Itoh Y, Tanaka E, Mochida S, Honda M, Hiasa Y, Koike A, Sugauchi F, Kaneko S, Izumi N, Tokunaga K, Mizokami M: Genome-wide association study identified ITPA/DDRGK1 variants reflecting thrombocytopenia in pegylated interferon and ribavirin therapy for chronic hepatitis C. Human Molecular Genetics 2011; 20 (17):3507-3516.
  15. Hiramatsu N, Kurosaki M, Sakamoto N, Iwasaki M, Sakamoto M, Suzuki Y, Sugauchi F, Tamori A, Kakinnuma S, Matsuura K, and Izumi N: Pretreatment Prediction of Anemia Progression by Peginterferon Plus Ribavirin Therapy in Chronic Hepatitis C: Decision-Tree Analysis. J Gastroenterol 2011; 46 (9): 1111-1119.
  16. Kadokura M, Maekawa S, Sueki R, Miura M, Komase K, Shindo H, Amemiya F, Uetake T, Inoue T, Sakamoto M, Nakagawa M, Sakamoto N, Watanabe M, Enomoto N: Analysis of the complete open reading frame of genotype 2b hepatitis C virus in association with the response to peginterferon and ribavirin therapy. PLoS One 2011;6 (9):e24514.
  17. Kurosaki M, Sakamoto N, Iwasaki M, Sakamoto M, Suzuki Y, Hiramatsu N, Sugauchi F, Yatsuhashi H, Izumi N. Pretreatment prediction of response to peginterferon plus ribavirin therapy in genotype 1 chronic hepatitis C using data mining analysis. J Gastroenterol 2011; 46(3):401-409.
  18. Yoshida T, Kondoh M, Ojima M, Mizuguchi H, Yamagishi Y, Sakamoto N, Yagi K. Adenovirus vector-mediated assay system for hepatitis C virus replication. Nucleic Acids Res 2011; 39(10):e64.
  19. Funaoka Y, Sakamoto N, Nakagawa M, Kakinuma S, Suda S, Watanabe T, Nitta S, Kitazume A, Kiyohashi K, Murakawa M, Azuma S, Tsuchiya K, and Watanabe M: Analysis of interferon signaling by infectious hepatitis C virus clones with substitutions of core amino acids 70 and 91. J Virol 2011; 85(12):5986-5994.
  20. Watanabe T, Sakamoto N, Nakagawa M, Kakinuma S, Itsui Y, Nishimura-Sakurai Y, Ueyama M, Funaoka Y, Kitazume A, Nitta S, Kiyohashi K, Murakawa M, Azuma S, Tsuchiya K, Oooka S, Watanabe M. The inhibitory effect on hepatitis C virus infection of a triterpenoid compound, with or without interferon-alpha. Antimicrob Agents Chemother 2011; 55(6):2537-2545.
  21. Yamamoto M, Sakamoto N, Nakamura T, Itsui Y, Nakagawa M, Nishimura-Sakurai Y, Kakinuma S, Azuma S, Tsuchiya K, Kato T, Wakita T, Watanabe M. Studies on virus kinetics using infectious fluorescence-tagged hepatitis C virus cell culture. Hepatol Res 2011;41:258-269.
  22. Toyoda M, Kitaoka A, Machida K, Nishinakagawa T, Yada R, Kohjima M, Kato M, Kotoh K, Sakamoto N, Shiota G, Nakamuta M, Nakashima M, Enjoji M. Association between lipid accumulation and the cannabinoid system in Huh7 cells expressing HCV genes. Int J Mol Med 2011;27:619-624.
  23. Sakamoto N, Nakagawa M, Tanaka Y, Sekine-Osajima Y, Ueyama M, Kurosaki M, Nishida N, Tamori A, Yuki NS, Itsui Y, Azuma S, Kakinuma S, Hige S, Itoh Y, Tanaka E, Hiasa Y, Izumi N, Tokunaga K, Mizokami M, Watanabe M. Association of IL28B variants with response to pegylated-interferon alpha plus ribavirin combination therapy reveals intersubgenotypic differences between genotypes 2a and 2b. J Med Virol 2011;83:871-878.
  24. Onozuka I, Kakinuma S, Kamiya A, Miyoshi M, Sakamoto N, Kiyohashi K, Watanabe T, Funaoka Y, Ueyama M, Nakagawa M, Koshikawa N, Seiki M, Nakauchi H, Watanabe M. Cholestatic liver fibrosis and toxin-induced fibrosis are exacerbated in matrix metalloproteinase-2 deficient mice. Biochem Biophys Res Commun 2011;406:134-140.
  25. Kurosaki M, Tanaka Y, Nishida N, Sakamoto N, Enomoto N, Honda M, Sugiyama M, Matsuura K, Sugauchi F, Asahina Y, Nakagawa M, Watanabe M, Sakamoto M, Maekawa S, Sakai A, Kaneko S, Ito K, Masaki N, Tokunaga K, Izumi N, Mizokami M. Pre-treatment prediction of response to pegylated-interferon plus ribavirin for chronic hepatitis C using genetic polymorphism in IL28B and viral factors. J Hepatol 2011;54:439-448.
  26. Kurosaki M, Sakamoto N, Iwasaki M, Sakamoto M, Suzuki Y, Hiramatsu N, Sugauchi F, Tamori A, Nakagawa M, Izumi N. Sequences in the interferon sensitivity-determining region and core region of hepatitis C virus impact pretreatment prediction of response to PEG-interferon plus ribavirin: data mining analysis. J Med Virol 2011;83:445-452.
  27. Iwasaki M, Tsuchiya K, Okamoto R, Zheng X, Kano Y, Okamoto E, Okada E, Araki A, Suzuki S, Sakamoto N, Kitagaki K, Akashi T, Eishi Y, Nakamura T, Watanabe M. Longitudinal cell formation in the entire human small intestine is correlated with the localization of Hath1 and Klf4. J Gastroenterol 2011;46:191-202.
  28. Suda G, Sakamoto N, Itsui Y, Nakagawa M, Tasaka-Fujita M, Funaoka Y, Watanabe T, Nitta S, Kiyohashi K, Azuma S, Kakinuma S, Tsuchiya K, Imamura M, Hiraga N, Chayama K, Watanabe M. IL-6-mediated intersubgenotypic variation of interferon sensitivity in hepatitis C virus genotype 2a/2b chimeric clones. Virology 2010;407:80-90.
  29. Sakamoto N, Tanaka Y, Nakagawa M, Yatsuhashi H, Nishiguchi S, Enomoto N, Azuma S, Nishimura-Sakurai Y, Kakinuma S, Nishida N, Tokunaga K, Honda M, Ito K, Mizokami M, Watanabe M. ITPA gene variant protects against anemia induced by pegylated interferon-alpha and ribavirin therapy for Japanese patients with chronic hepatitis C. Hepatol Res 2010;40:1063-1071.
  30. Nishimura-Sakurai Y, Sakamoto N, Mogushi K, Nagaie S, Nakagawa M, Itsui Y, Tasaka-Fujita M, Onuki-Karakama Y, Suda G, Mishima K, Yamamoto M, Ueyama M, Funaoka Y, Watanabe T, Azuma S, Sekine-Osajima Y, Kakinuma S, Tsuchiya K, Enomoto N, Tanaka H, Watanabe M. Comparison of HCV-associated gene expression and cell signaling pathways in cells with or without HCV replicon and in replicon-cured cells. J Gastroenterol 2010;45:523-536.
  31. Nakagawa M, Sakamoto N, Ueyama M, Mogushi K, Nagaie S, Itsui Y, Azuma S, Kakinuma S, Tanaka H, Enomoto N, Watanabe M. Mutations in the interferon sensitivity determining region and virological response to combination therapy with pegylated-interferon alpha 2b plus ribavirin in patients with chronic hepatitis C-1b infection. J Gastroenterol 2010;45:656-665.
  32. Mizui T, Yamashina S, Tanida I, Takei Y, Ueno T, Sakamoto N, Ikejima K, Kitamura T, Enomoto N, Sakai T, Kominami E, Watanabe S. Inhibition of hepatitis C virus replication by chloroquine targeting virus-associated autophagy. J Gastroenterol 2010;45:195-203.
  33. Mishima K, Sakamoto N, Sekine-Osajima Y, Nakagawa M, Itsui Y, Azuma S, Kakinuma S, Kiyohashi K, Kitazume A, Tsuchiya K, Imamura M, Hiraga N, Chayama K, Wakita T, Watanabe M. Cell culture and in vivo analyses of cytopathic hepatitis C virus mutants. Virology 2010;405:361-369.
  34. Kim K, Kim KH, Kim HY, Cho HK, Sakamoto N, Cheong J. Curcumin inhibits hepatitis C virus replication via suppressing the Akt-SREBP-1 pathway. FEBS Lett 2010;584:707-712.
  35. Karakama Y, Sakamoto N, Itsui Y, Nakagawa M, Tasaka-Fujita M, Nishimura-Sakurai Y, Kakinuma S, Oooka M, Azuma S, Tsuchiya K, Onogi H, Hagiwara M, Watanabe M. Inhibition of hepatitis C virus replication by a specific inhibitor of serine-arginine-rich protein kinase. Antimicrob Agents Chemother 2010;54:3179-3186.
  36. Kameyama K, Nemoto Y, Kanai T, Shinohara T, Okamoto R, Tsuchiya K, Nakamura T, Sakamoto N, Totsuka T, Hibi T, Watanabe M. IL-2 is positively involved in the development of colitogenic CD4+ IL-7R alpha high memory T cells in chronic colitis. Eur J Immunol 2010;40:2423-2436.
  37. Wang SY, Tseng CP, Tsai KC, Lin CF, Wen CY, Tsay HS, Sakamoto N, Tseng CH, Cheng JC. Bioactivity-guided screening identifies pheophytin a as a potent anti-hepatitis C virus compound from Lonicera hypoglauca Miq. Biochem Biophys Res Commun 2009;385:230-235.
  38. Totsuka T, Kanai T, Nemoto Y, Tomita T, Okamoto R, Tsuchiya K, Nakamura T, Sakamoto N, Akiba H, Okumura K, Yagita H, Watanabe M. RANK-RANKL signaling pathway is critically involved in the function of CD4+CD25+ regulatory T cells in chronic colitis. J Immunol 2009;182:6079-6087.
  39. Tomita T, Kanai T, Totsuka T, Nemoto Y, Okamoto R, Tsuchiya K, Sakamoto N, Ohteki T, Hibi T, Watanabe M. IL-7 is essential for lymphopenia-driven turnover of colitogenic CD4(+) memory T cells in chronic colitis. Eur J Immunol 2009;39:2737-2747.
  40. Toma S, Yamashiro T, Arakaki S, Shiroma J, Maeshiro T, Hibiya K, Sakamoto N, Kinjo F, Tateyama M, Fujita J. Inhibition of intracellular hepatitis C virus replication by nelfinavir and synergistic effect with interferon-alpha. J Viral Hepat 2009;16:506-512.
  41. Tanaka Y, Nishida N, Sugiyama M, Kurosaki M, Matsuura K, Sakamoto N, Nakagawa M, Korenaga M, Hino K, Hige S, Ito Y, Mita E, Tanaka E, Mochida S, Murawaki Y, Honda M, Sakai A, Hiasa Y, Nishiguchi S, Koike A, Sakaida I, Imamura M, Ito K, Yano K, Masaki N, Sugauchi F, Izumi N, Tokunaga K, Mizokami M. Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet 2009;41:1105-1109.
  42. Tai AW, Benita Y, Peng LF, Kim SS, Sakamoto N, Xavier RJ, Chung RT. A functional genomic screen identifies cellular cofactors of hepatitis C virus replication. Cell Host Microbe 2009;5:298-307.
  43. Sekine-Osajima Y, Sakamoto N, Nakagawa M, Itsui Y, Tasaka M, Nishimura-Sakurai Y, Chen CH, Suda G, Mishima K, Onuki Y, Yamamoto M, Maekawa S, Enomoto N, Kanai T, Tsuchiya K, Watanabe M. Two flavonoids extracts from Glycyrrhizae radix inhibit in vitro hepatitis C virus replication. Hepatol Res 2009;39:60-69.
  44. Sakamoto N, Wu GY. Prospects for future therapy of hepatitis C virus infection. Future Virology 2009;4:453-462.
  45. Sakamoto N, Watanabe M. New therapeutic approaches to hepatitis C virus. J Gastroenterol 2009;44:643-649.
  46. Onizawa M, Nagaishi T, Kanai T, Nagano K, Oshima S, Nemoto Y, Yoshioka A, Totsuka T, Okamoto R, Nakamura T, Sakamoto N, Tsuchiya K, Aoki K, Ohya K, Yagita H, Watanabe M. Signaling pathway via TNF-alpha/NF-kappaB in intestinal epithelial cells may be directly involved in colitis-associated carcinogenesis. Am J Physiol Gastrointest Liver Physiol 2009;296:G850-859.
  47. Ohira M, Ishiyama K, Tanaka Y, Doskali M, Igarashi Y, Tashiro H, Hiraga N, Imamura M, Sakamoto N, Asahara T, Chayama K, Ohdan H. Adoptive immunotherapy with liver allograft-derived lymphocytes induces anti-HCV activity after liver transplantation in humans and humanized mice. J Clin Invest 2009;119:3226-3235.
  48. Nemoto Y, Kanai T, Kameyama K, Shinohara T, Sakamoto N, Totsuka T, Okamoto R, Tsuchiya K, Nakamura T, Sudo T, Matsumoto S, Watanabe M. Long-lived colitogenic CD4+ memory T cells residing outside the intestine participate in the perpetuation of chronic colitis. J Immunol 2009;183:5059-5068.
  49. Murayama M, Okamoto R, Tsuchiya K, Akiyama J, Nakamura T, Sakamoto N, Kanai T, Watanabe M. Musashi-1 suppresses expression of Paneth cell-specific genes in human intestinal epithelial cells. J Gastroenterol 2009;44:173-182.
  50. Kim K, Kim KH, Ha E, Park JY, Sakamoto N, Cheong J. Hepatitis C virus NS5A protein increases hepatic lipid accumulation via induction of activation and expression of PPARgamma. FEBS Lett 2009;583:2720-2726.
  51. Itsui Y, Sakamoto N, Kakinuma S, Nakagawa M, Sekine-Osajima Y, Tasaka-Fujita M, Nishimura-Sakurai Y, Suda G, Karakama Y, Mishima K, Yamamoto M, Watanabe T, Ueyama M, Funaoka Y, Azuma S, Watanabe M. Antiviral effects of the interferon-induced protein guanylate binding protein 1 and its interaction with the hepatitis C virus NS5B protein. Hepatology 2009;50:1727-1737.
  52. Chatterji U, Bobardt M, Selvarajah S, Yang F, Tang H, Sakamoto N, Vuagniaux G, Parkinson T, Gallay P. The isomerase active site of cyclophilin A is critical for hepatitis C virus replication. J Biol Chem 2009;284:16998-17005.
  53. Totsuka T, Kanai T, Nemoto Y, Tomita T, Tsuchiya K, Sakamoto N, Okamoto R, Watanabe M. Immunosenescent colitogenic CD4(+) T cells convert to regulatory cells and suppress colitis. Eur J Immunol 2008;38:1275-1286.
  54. Tomita T, Kanai T, Nemoto Y, Totsuka T, Okamoto R, Tsuchiya K, Sakamoto N, Watanabe M. Systemic, but not intestinal, IL-7 is essential for the persistence of chronic colitis. J Immunol 2008;180:383-390.
  55. Tomita T, Kanai T, Nemoto Y, Fujii T, Nozaki K, Okamoto R, Tsuchiya K, Nakamura T, Sakamoto N, Totsuka T, Watanabe M. Colitogenic CD4+ effector-memory T cells actively recirculate in chronic colitic mice. Inflamm Bowel Dis 2008;14:1630-1640.
  56. Tomita T, Kanai T, Fujii T, Nemoto Y, Okamoto R, Tsuchiya K, Totsuka T, Sakamoto N, Watanabe M. Continuous generation of colitogenic CD4(+) T cells in persistent colitis. Eur J Immunol 2008;39:1264-1274.
  57. Tomita T, Kanai T, Fujii T, Nemoto Y, Okamoto R, Tsuchiya K, Totsuka T, Sakamoto N, Akira S, Watanabe M. MyD88-dependent pathway in T cells directly modulates the expansion of colitogenic CD4+ T cells in chronic colitis. J Immunol 2008;180:5291-5299.
  58. Sekine-Osajima Y, Sakamoto N, Mishima K, Nakagawa M, Itsui Y, Tasaka M, Nishimura-Sakurai Y, Chen CH, Kanai T, Tsuchiya K, Wakita T, Enomoto N, Watanabe M. Development of plaque assays for hepatitis C virus-JFH1 strain and isolation of mutants with enhanced cytopathogenicity and replication capacity. Virology 2008;371:71-85.
  59. Sakamoto N, Tanabe Y, Yokota T, Satoh K, Sekine-Osajima Y, Nakagawa M, Itsui Y, Tasaka M, Sakurai Y, Cheng-Hsin C, Yano M, Ohkoshi S, Aoyagi Y, Maekawa S, Enomoto N, Kohara M, Watanabe M. Inhibition of hepatitis C virus infection and expression in vitro and in vivo by recombinant adenovirus expressing short hairpin RNA. J Gastroenterol Hepatol 2008;23:1437-1447.
  60. Ohashi K, Sakamoto N, Watanabe M, Mizushima H, Tanaka H. Development of a telediagnosis endoscopy system over secure internet. Methods Inf Med 2008;47:157-166.
  61. Nemoto Y, Kanai T, Tohda S, Totsuka T, Okamoto R, Tsuchiya K, Nakamura T, Sakamoto N, Fukuda T, Miura O, Yagita H, Watanabe M. Negative feedback regulation of colitogenic CD4+ T cells by increased granulopoiesis. Inflamm Bowel Dis 2008;14:1491-1503.
  62. Nanmoku K, Imaizumi R, Tojimbara T, Nakajima I, Fuchinoue S, Sakamoto N, Watanabe M, Teraoka S. Effects of immunosuppressants on the progression of hepatitis C in hepatitis C virus-positive renal transplantation and the usefulness of interferon therapy. Transplant Proc 2008;40:2382-2385.
  63. Jin H, Yamashita A, Maekawa S, Yang P, He L, Takayanagi S, Wakita T, Sakamoto N, Enomoto N, Ito M. Griseofulvin, an oral antifungal agent, suppresses hepatitis C virus replication in vitro. Hepatol Res 2008;38:909-918.
  64. Ito Y, Kanai T, Totsuka T, Okamoto R, Tsuchiya K, Nemoto Y, Yoshioka A, Tomita T, Nagaishi T, Sakamoto N, Sakanishi T, Okumura K, Yagita H, Watanabe M. Blockade of NKG2D signaling prevents the development of murine CD4+ T cell-mediated colitis. Am J Physiol Gastrointest Liver Physiol 2008;294:G199-207.
  65. Fujii T, Tomita T, Kanai T, Nemoto Y, Totsuka T, Sakamoto N, Nakamura T, Tsuchiya K, Okamoto R, Watanabe M. FTY720 suppresses the development of colitis in lymphoid-null mice by modulating the trafficking of colitogenic CD4+ T cells in bone marrow. Eur J Immunol 2008;38:3290-3303.
  66. Asahina Y, Izumi N, Hirayama I, Tanaka T, Sato M, Yasui Y, Komatsu N, Umeda N, Hosokawa T, Ueda K, Tsuchiya K, Nakanishi H, Itakura J, Kurosaki M, Enomoto N, Tasaka M, Sakamoto N, Miyake S. Potential relevance of cytoplasmic viral sensors and related regulators involving innate immunity in antiviral response. Gastroenterology 2008;134:1396-1405.
  67. Aragaki M, Tsuchiya K, Okamoto R, Yoshioka S, Nakamura T, Sakamoto N, Kanai T, Watanabe M. Proteasomal degradation of Atoh1 by aberrant Wnt signaling maintains the undifferentiated state of colon cancer. Biochem Biophys Res Commun 2008;368:923-929.
  68. Amemiya F, Maekawa S, Itakura Y, Kanayama A, Matsui A, Takano S, Yamaguchi T, Itakura J, Kitamura T, Inoue T, Sakamoto M, Yamauchi K, Okada S, Yamashita A, Sakamoto N, Itoh M, Enomoto N. Targeting lipid metabolism in the treatment of hepatitis C virus infection. J Infect Dis 2008;197:361-370.
  69. Tasaka M, Sakamoto N, Itakura Y, Nakagawa M, Itsui Y, Sekine-Osajima Y, Nishimura-Sakurai Y, Chen CH, Yoneyama M, Fujita T, Wakita T, Maekawa S, Enomoto N, Watanabe M. Hepatitis C virus non-structural proteins responsible for suppression of the RIG-I/Cardif-induced interferon response. J Gen Virol 2007;88:3323-3333.
  70. Sakamoto N, Yoshimura M, Kimura T, Toyama K, Sekine-Osajima Y, Watanabe M, Muramatsu M. Bone morphogenetic protein-7 and interferon-alpha synergistically suppress hepatitis C virus replicon. Biochem Biophys Res Commun 2007;357:467-473.
  71. Peng LF, Kim SS, Matchacheep S, Lei X, Su S, Lin W, Runguphan W, Choe WH, Sakamoto N, Ikeda M, Kato N, Beeler AB, Porco JA, Jr., Schreiber SL, Chung RT. Identification of novel epoxide inhibitors of hepatitis C virus replication using a high-throughput screen. Antimicrob Agents Chemother 2007;51:3756-3759.
  72. Kim SS, Peng LF, Lin W, Choe WH, Sakamoto N, Kato N, Ikeda M, Schreiber SL, Chung RT. A cell-based, high-throughput screen for small molecule regulators of hepatitis C virus replication. Gastroenterology 2007;132:311-320.
  73. Kakinuma S, Asahina K, Okamura K, Teramoto K, Tateno C, Yoshizato K, Tanaka Y, Yasumizu T, Sakamoto N, Watanabe M, Teraoka H. Human cord blood cells transplanted into chronically damaged liver exhibit similar characteristics to functional hepatocytes. Transplant Proc 2007;39:240-243.
  74. Yamashiro T, Sakamoto N, Kurosaki M, Kanazawa N, Tanabe Y, Nakagawa M, Chen CH, Itsui Y, Koyama T, Takeda Y, Maekawa S, Enomoto N, Sakugawa H, Watanabe M. Negative regulation of intracellular hepatitis C virus replication by interferon regulatory factor 3. J Gastroenterol 2006;41:750-757.
  75. Koyama T, Sakamoto N, Tanabe Y, Nakagawa M, Itsui Y, Takeda Y, Kakinuma S, Sekine Y, Maekawa S, Yanai Y, Kurimoto M, Watanabe M. Divergent activities of interferon-alpha subtypes against intracellular hepatitis C virus replication. Hepatol Res 2006;34:41-49.
  76. Kohashi T, Maekawa S, Sakamoto N, Kurosaki M, Watanabe H, Tanabe Y, Chen CH, Kanazawa N, Nakagawa M, Kakinuma S, Yamashiro T, Itsui Y, Koyama T, Enomoto N, Watanabe M. Site-specific mutation of the interferon sensitivity-determining region (ISDR) modulates hepatitis C virus replication. J Viral Hepat 2006;13:582-590.
  77. Itsui Y, Sakamoto N, Kurosaki M, Kanazawa N, Tanabe Y, Koyama T, Takeda Y, Nakagawa M, Kakinuma S, Sekine Y, Maekawa S, Enomoto N, Watanabe M. Expressional screening of interferon-stimulated genes for antiviral activity against hepatitis C virus replication. J Viral Hepat 2006;13:690-700.
  78. Tanabe Y, Nagayama K, Enomoto N, Izumi N, Tazawa J, Kurosaki M, Sakamoto N, Sato C, Watanabe M. Characteristic sequence changes of hepatitis C virus genotype 2b associated with sustained biochemical response to IFN therapy. J Viral Hepat 2005;12:251-261.
  79. Nakagawa M, Sakamoto N, Tanabe Y, Koyama T, Itsui Y, Takeda Y, Chen CH, Kakinuma S, Oooka S, Maekawa S, Enomoto N, Watanabe M. Suppression of hepatitis C virus replication by cyclosporin a is mediated by blockade of cyclophilins. Gastroenterology 2005;129:1031-1041.
  80. Itakura J, Nagayama K, Enomoto N, Hamano K, Sakamoto N, Fanning LJ, Kenny-Walsh E, Shanahan F, Watanabe M. Viral load change and sequential evolution of entire hepatitis C virus genome in Irish recipients of single source-contaminated anti-D immunoglobulin*. J Viral Hepat 2005;12:594-603.
  81. Hamano K, Sakamoto N, Enomoto N, Izumi N, Asahina Y, Kurosaki M, Ueda E, Tanabe Y, Maekawa S, Itakura J, Watanabe H, Kakinuma S, Watanabe M. Mutations in the NS5B region of the hepatitis C virus genome correlate with clinical outcomes of interferon-alpha plus ribavirin combination therapy. J Gastroenterol Hepatol 2005;20:1401-1409.
  82. Chen CH, Nagayama K, Enomoto N, Miyasaka Y, Kurosaki M, Sakamoto N, Maekawa S, Kakinuma S, Ikeda T, Izumi N, Sato C, Watanabe M. Enhancement of mitochondrial gene expression in the liver of primary biliary cirrhosis. Hepatol Res 2005;31:24-30.
  83. Ueda E, Enomoto N, Sakamoto N, Hamano K, Sato C, Izumi N, Watanabe M. Changes of HCV quasispecies during combination therapy with interferon and ribavirin. Hepatol Res 2004;29:89-96.
  84. Tanabe Y, Sakamoto N, Enomoto N, Kurosaki M, Ueda E, Maekawa S, Yamashiro T, Nakagawa M, Chen CH, Kanazawa N, Kakinuma S, Watanabe M. Synergistic inhibition of intracellular hepatitis C virus replication by combination of ribavirin and interferon- alpha. J Infect Dis 2004;189:1129-1139.
  85. Tamamori-Adachi M, Hayashida K, Nobori K, Omizu C, Yamada K, Sakamoto N, Kamura T, Fukuda K, Ogawa S, Nakayama KI, Kitajima S. Down-regulation of p27Kip1 promotes cell proliferation of rat neonatal cardiomyocytes induced by nuclear expression of cyclin D1 and CDK4. Evidence for impaired Skp2-dependent degradation of p27 in terminal differentiation. J Biol Chem 2004;279:50429-50436.
  86. Takenawa H, Kurosaki M, Enomoto N, Miyasaka Y, Kanazawa N, Sakamoto N, Ikeda T, Izumi N, Sato C, Watanabe M. Differential gene-expression profiles associated with gastric adenoma. Br J Cancer 2004;90:216-223.
  87. Nakagawa M, Sakamoto N, Enomoto N, Tanabe Y, Kanazawa N, Koyama T, Kurosaki M, Maekawa S, Yamashiro T, Chen CH, Itsui Y, Kakinuma S, Watanabe M. Specific inhibition of hepatitis C virus replication by cyclosporin A. Biochem Biophys Res Commun 2004;313:42-47.
  88. Maekawa S, Enomoto N, Sakamoto N, Kurosaki M, Ueda E, Kohashi T, Watanabe H, Chen CH, Yamashiro T, Tanabe Y, Kanazawa N, Nakagawa M, Sato C, Watanabe M. Introduction of NS5A mutations enables subgenomic HCV replicon derived from chimpanzee-infectious HC-J4 isolate to replicate efficiently in Huh-7 cells. J Viral Hepat 2004;11:394-403.
  89. Kanazawa N, Kurosaki M, Sakamoto N, Enomoto N, Itsui Y, Yamashiro T, Tanabe Y, Maekawa S, Nakagawa M, Chen CH, Kakinuma S, Oshima S, Nakamura T, Kato T, Wakita T, Watanabe M. Regulation of hepatitis C virus replication by interferon regulatory factor 1. J Virol 2004;78:9713-9720.
  90. Yokota T, Sakamoto N, Enomoto N, Tanabe Y, Miyagishi M, Maekawa S, Yi L, Kurosaki M, Taira K, Watanabe M, Mizusawa H. Inhibition of intracellular hepatitis C virus replication by synthetic and vector-derived small interfering RNAs. EMBO Rep 2003;5:602-608.
  91. Miyasaka Y, Enomoto N, Kurosaki M, Sakamoto N, Kanazawa N, Kohashi T, Ueda E, Maekawa S, Watanabe H, Izumi N, Sato C, Watanabe M. Hepatitis C virus nonstructural protein 5A inhibits tumor necrosis factor-alpha-mediated apoptosis in Huh7 cells. J Infect Dis 2003;188:1537-1544.
  92. Nagayama K, Enomoto N, Miyasaka Y, Kurosaki M, Chen CH, Sakamoto N, Nakagawa M, Sato C, Tazawa J, Ikeda T, Izumi N, Watanabe M. Overexpression of interferon gamma-inducible protein 10 in the liver of patients with type I autoimmune hepatitis identified by suppression subtractive hybridization. Am J Gastroenterol 2001;96:2211-2217.
  93. Itakura J, Nagayama K, Enomoto N, Sakamoto N, Tazawa J, Izumi N, Marumo F, Sato C. CD81 nucleotide mutation in hepatocellular carcinoma and lack of CD81 polymorphism in patients at stages of hepatitis C virus infection. J Med Virol 2001;63:22-28.
  94. Sakamoto N, Koizumi K, Asahina Y, Tazawa J, Maeda M, Marumo F, Sato C. Primary Budd-Chiari syndrome due to complex venous anomalies. Abdom Imaging 1997;22:499-501.
  95. Sakamoto N, Wu CH, Wu GY. Intracellular cleavage of hepatitis C virus RNA and inhibition of viral protein translation by hammerhead ribozymes. J Clin Invest 1996;98:2720-2728.
  96. Sakamoto N, Enomoto N, Kurosaki M, Asahina Y, Maekawa S, Koizumi K, Sakuma I, Murakami T, Marumo F, Sato C. Comparison of the hypervariable region of hepatitis C virus genomes in plasma and liver. J Med Virol 1995;46:7-11.
  97. Kurosaki M, Enomoto N, Sakamoto N, Tanaka Y, Tang L, Hoshino Y, Izumi N, Marumo F, Sato C. Detection and analysis of replicating hepatitis C virus RNA in hepatocellular carcinoma tissues. J Hepatol 1995;22:527-535.
  98. Kobayashi F, Ikeda T, Sakamoto N, Kurosaki M, Tozuka S, Sakamoto S, Fukuma T, Marumo F, Sato C. Severe chronic active hepatitis induced by UFTR containing tegafur and uracil. Dig Dis Sci 1995;40:2434-2437.
  99. Sakamoto N, Enomoto N, Kurosaki M, Marumo F, Sato C. Sequential change of the hypervariable region of the hepatitis C virus genome in acute infection. J Med Virol 1994;42:103-108.
  100. Sakamoto N, Enomoto N, Kurosaki M, Marumo F, Sato C. Detection and quantification of hepatitis C virus RNA replication in the liver. J Hepatol 1994;20:593-597.
  101. Sakamoto N, Sato C, Haritani H, Maekawa S, Kurosaki M, Enomoto N, Hoshino Y, Tazawa J, Nishimura M, Marumo F. Detection of hepatitis C viral RNA in sporadic acute non-A, non-B hepatitis by polymerase chain reaction. Its usefulness for the early diagnosis of seronegative infection. J Hepatol 1993;17:28-33.
  102. Sakamoto N, Enomoto N, Marumo F, Sato C. Prevalence of hepatitis C virus infection among long-term hemodialysis patients: detection of hepatitis C virus RNA in plasma. J Med Virol 1993;39:11-15.
  103. Kurosaki M, Enomoto N, Sato C, Sakamoto N, Hoshino Y, Haritani H, Marumo F. Correlation of plasma hepatitis C virus RNA levels with serum alanine aminotransferase in non-A, non-B chronic liver disease. J Med Virol 1993;39:246-250.
  104. Hoshino Y, Enomoto N, Sakamoto N, Kurosaki M, Ikeda T, Marumo F, Sato C. Expression of the hepatocyte growth factor receptor in the regenerating rat liver. Cancer Lett 1993;71:119-123.
  105. Enomoto N, Sakamoto N, Kurosaki M, Marumo F, Sato C. The hypervariable region of the HCV genome changes sequentially during the progression of acute HCV infection to chronic hepatitis. J Hepatol 1993;17:415-416.