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HOME > 組織・メンバー > 笹月健彦
笹月健彦
氏  名
笹月 健彦
生年月日
昭和15年4月21日
現  職
九州大学高等研究院特別主幹教授

文部科学省新学術領域研究「HLA進化と疾病」

現在の研究
  • HLAを中心に据えたヒト免疫応答の制御および免疫関連疾患の制御の解明
業績(著書等)
  • 監訳 免疫生物学(南江堂)、エッセンシャル免疫学(メディカル・サイエンス・インターナショナル)
研究課題と主な論文
学歴と職歴はこちらから学歴と職歴はこちらから
Ⅰ. ヒトゲノムの中で最も多型性に富むHLA遺伝子群に支配されたHLA−A、B、C、DR、DQ、DP分子による免疫応答の制御機構の解明
  • Tanimura K, Jin H, Suenaga T, Morikami S, Arase N, Kishida K, Hirayasu K, Kohyama M, Ebina Y, Yasuda S, Horita T, Takasugi K, Ohmura K, Yamamoto K, Katayama I, Sasazuki T, Lanier LL, Atsumi T, Yamada H, Arase H. β2-Glycoprotein I/HLA class II complexes are novel autoantigens in antiphospholipid syndrome. Blood. 125(18):2835-44, 2015
  • Gotoh K, Tanaka Y, Nishikimi A, Inayoshi A, Enjoji M, Takayanagi R, Sasazuki T, Fukui Y. Differential requirement for DOCK2 in migration of plasmacytoid DCs versus myeloid DCs. Blood, 111(6):2973-2976, 2008.
  • Tanaka Y, Hamano S, Gotoh K, Murata Y, Kunisaki Y, Nishikimi A, Takii R, Kawaguchi M, Inayoshi A, Sasazuki T, Fukui Y. T helper type 2 differentiation and intracellular trafficking of the interleukin 4 receptor-α subunit controlled by the Rac activator Dock2. Nat. Immunol., 8(10):1067-75, 2007.
  • Sanui T, Inayoshi A, Noda M, Iwata E, Oike M, Sasazuki T, Fukui Y. DOCK2 is essential for antigen-induced translocation of TCR and lipid rafts, but not PKC-θ and LFA-1, in T cells. Immunity,, 19: 119-129, 2003
  • Fukui Y, Hashimoto O, Sanui T, Oono T, Koga H, Abe M, Inayoshi A, Noda M, Oike M, Shirai T, Sasazuki T. Hematopoietic cell-specific CDM family protein DOCK2 is essential for lymphocyte migration. Nature, 412: 826-831, 2001.
  • Oono T, Fukui Y, Masuko S, Hashimoto O, Ueno T, Sanui T, Inayoshi A, Noda M, Sata M, Sasazuki T. T-cell repertoire shaped by a single peptide-ligand causes organ-specific autoimmune disease depending on its thymic expression level. J. Clin. Invest., 108:1589-96, 2001
  • Fukui Y, Oono T, Cabaniols JP, Nakao K, Hirokawa K, Inayoshi A, Sanui T, Kanellopoulos J, Iwata E, Noda M, Katsuki M, Kourilsky P, Sasazuki T. Diversity of T cell repertoire shaped by a single peptide ligand is critically affected by its amino acid residue at a T cell receptor-contact. Proc. Natl. Acad. Sci. USA., 97:13760-13765, 2000
  • Fukui Y, Hashimoto O, Inayoshi A, Gyotoku T, Sano T, Koga T, Gushima T, Sasazuki T. Highly restricted T cell repertoire shaped by a single major histocompatibility complex-peptide ligand in the presence of a single rearranged T cell receptor βchain. J. Exp. Med., 188:897-907, 1998
  • Gapin L, Fukui Y, Kanellopoulos J, Sano T, Casrouge A, Malier V, Beaudoing E, Gautheret D, Claverie JM, Sasazuki T, Kourilsky P. Quantitative analysis of the T-cell repertoire by a single peptide/MHC complex. J. Exp. Med., 187: 1871-1883,1998
  • Fukui Y, Ishimoto T, Utsuyama M, Gyotoku T, Koga T, Nakao K, Hirokawa K, Katsuki M, Sasazuki T. Positive and negative CD4+ thymocyte selection by a single MHC class Ⅱ/peptide ligand affected by its expression level in the thymus. Immunity, 6: 401-410, 1997
  • Yamamoto K, Fukui Y, Esaki Y, Inamitsu T, Sudo T, Yamane K, Kamikawaji N, Kimura A, Sasazuki T. Functional interaction between human histocompatibility leukocyte antigen (HLA)class Ⅱ and mouse CD4 molecule in antigen recognition by T cells in HLA-DR and DQ transgenic mice. J. Exp. Med. 180: 165-171, 1994
  • Nishimura Y, Iwanaga T, Inamitsu T, Yanagawa Y, Yasunami M, Kimura A, Hirokawa K, Sasazuki T: Expression of human major histocompatibility complex, HLA-DQw6 genes alters the immune response in C57BL/6 mice. J. Immunol., 145:353-360, 1990
  • Sasazuki T, Iwanaga T, Inamitsu T, Yanagawa Y, Yasunami M, Kimura A, Hirokawa K, Nishimura Y. Expression and function of human major histocompatibility complex HLA-DQw6 genes in the C57BL/6 mouse. Cold Spring Harbor Symposium on Quantitative Biology, vol 54, 513-520, 1989
  • Sasazuki T, Kamikawaji N, Fujisawa K, Yoshizumi H, Yasunami M, Kimura A, Nishimura Y. Differential roles of HLA-DR and DQ in immune regulation. Progress in Immunology Ⅶ, Springer verlag, Berlin,. p853-860, 1989.
  • Hirayama K, Matsushita S, Kikuchi I, Iuchi M, Ohta N, Sasazuki T. HLA-DQ is epistatic to HLA-DR in controlling the immune response to schistosomal antigen in humans. Nature, 327: 426-430, 1987.
  • Hirayama K, Nishimura Y, Tsukamoto K, Sasazuki T. Functional and molecular analysis of three distinct HLA-DR4・- chains responsible for the MLR between HLA-Dw4, Dw15 and DKT2. J. Immunol., 137: 924-933, 1986.
  • Sone T, Tsukamoto K, Hirayama K, Nishimura Y, Takenouchi T, Aizawa M, Sasazuki T. Two distinct class II molecules encoded by the genes within HLA-DR subregion of HLA-Dw2 and Dw12 can act as stimulating and restriction molecules. J. Immunol., 135: 1288-1298, 1985.
  • Nishimura Y, Sasazuki T. Suppressor T cells control the HLA-linked low responsiveness to streprococcal antigen in man. Nature,, 301: 67-69, 1983.
  • Ohta N, Minai M, Sasazuki T. Antigen-specific suppressor T lymphocytes (Leu-2a+3a-)in human schistosomiasis japonica. J. Immunol., 131: 2524-2528, 1983.
  • Sasazuki T, Kaneoka H, Nishimura Y, Kaneoka T, Hayama M, Ohkuni H. An HLA-linked immune suppression gene in man. J. Exp. Med.,152: 297s-313s, 1980.
  • Sasazuki T, Kohno Y, Iwamoto I, Tanimura M, Naito S. Association between an HLA haplotype and low responsiveness to tetanus toxoid in man. Nature, 272: 359-361, 1978.
  • Fuks S, Strober S, Bobrove AM, Sasazuki T, McMichael A, Kaplan H. Long term effects of radiation on T and B lymphocytes in peripheral bolld of patients with Hodgkin's Disease. J. Clin. Invest., 58: 803-814, 1974.
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Ⅱ. HLAによる自己免疫疾患、アレルギーなど免疫関連疾患発症機構の解明
  • Sasazuki T, Inoko H, Morishima S, Morishima Y. Gene Map of the HLA Region, Graves' Disease and Hashimoto Thyroiditis, and Hematopoietic Stem Cell Transplantation. Adv Immunol. 129:175-249, 2016
  • Nishida N, Ohashi J, Sugiyama M, Tsuchiura T, Yamamoto K, Hino K, Honda M, Kaneko S, Yatsuhashi H, Koike K, Yokosuka O, Tanaka E, Taketomi A, Kurosaki M, Izumi N, Sakamoto N, Eguchi Y, Sasazuki T, Tokunaga K, Mizokami M. Effects of HLA-DPB1 genotypes on chronic hepatitis B infection in Japanese individuals. Tissue Antigens. 86(6):406-12, 2015
  • Tochio N, Umehara T, Nakabayashi K, Yoneyama M, Tsuda K, Shirouzu M, Koshiba S, Watanabe S, Kigawa T, Sasazuki T, Shirasawa S, Yokoyama S. Solution structures of the DNA-binding domains of immune-related zinc-finger protein ZFAT. J Struct Funct Genomics.16(2):55-65, 2015
  • Oryoji D, Ueda S, Yamamoto K, Yoshimura Noh J, Okamura K, Noda M, Watanabe N, Yoshihara A, Ito K, Sasazuki T.Identification of a Hashimoto thyroiditis susceptibility locus via a genome-wide comparison with Graves' disease. J Clin Endocrinol Metab. 100(2):E319-24, 2015
  • Oryoji D, Hisamatsu T, Tsuchiya K, Umeno J, Ueda S, Yamamoto K, Matsumoto T, Watanabe M, Hibi T, Sasazuki T. Associations of HLA class I alleles in Japanese patients with Crohn's disease. Genes Immun. 16(1):54-6, 2015
  • Jin H, Arase N, Hirayasu K, Kohyama M, Suenaga T, Saito F, Tanimura K, Matsuoka S, Ebina K, Shi K, Toyama-Sorimachi N, Yasuda S, Horita T, Hiwa R, Takasugi K, Ohmura K, Yoshikawa H, Saito T, Atsumi T, Sasazuki T, Katayama I, Lanier LL, Arase H. Autoantibodies to IgG/HLA class Ⅱ complexes are associated with rheumatoid arthritis susceptibility. Proc Natl Acad Sci U S A. 111(10):3787-92, 2014
  • Kawano M, Nakayama M, Aoshima Y, Nakamura K, Ono M, Nishiya T, Nakamura S, Takeda Y, Dobashi A, Takahashi A, Endo M, Ito A, Ueda K, Sato N, Higuchi S, Kondo T, Hashimoto S, Watanabe M, Watanabe M, Takahashi T, Sasaki K, Nakamura M, Sasazuki T, Narushima T, Suzuki R, Ogasawara K. NKG2D⁺ IFN-γ⁺ CD8⁺ T cells are responsible for palladium allergy. PLoS One. 9(2):e86810, 2014
  • Ueda S, Oryoji D, Yamamoto K, Noh JY, Okamura K, Noda M, Kashiwase K, Kosuga Y, Sekiya K, Inoue K, Yamada H, Oyamada A, Nishimura Y, Yoshikai Y, Ito K, Sasazuki T.
    Identification of independent susceptible and protective HLA alleles in Japanese autoimmune thyroid disease and their epistasis.
    J Clin Endocrinol Metab. 99(2):E379-83, 2014
  • Ogawa M, Okamura T, Ishikura S, Doi K, Matsuzaki H, Tanaka Y, Ota T, Hayakawa K, Suzuki H, Tsunoda T, Sasazuki T, Shirasawa S. Zfat-Deficiency Results in a Loss of CD3ζ Phosphorylation with Dysregulation of ERK and Egr Activities Leading to Impaired Positive Selection. PLoS One. 8(10):e76254, 2013
  • Doi K, Fujimoto T, Okamura T, Ogawa M, Tanaka Y, Mototani Y, Goto M, Ota T, Matsuzaki H, Kuroki M, Tsunoda T, Sasazuki T, Shirasawa S. ZFAT plays critical roles in peripheral T cell homeostasis and its T cell receptor-mediated response. Biochem Biophys Res Commun. 425(1):107-12, 2012
  • Kochi Y, Yamada R, Suzuki A, Harley JB, Shirasawa S, Sawada T, Bae S-C, Tokuhiro S, Chang X, Sekine A, Takahashi A, Tsunoda T, Ohnishi Y, Kaufman KM, Kang CP, Kang C, Otsubo S, Yumura W, Mimori A, Koike T, Nakamura Y, Sasazuki T, Yamamoto K. A functional variant in FcRH3, encoding Fc Receptor Homolog 3, is associated with rheumatoid arthritis and several autoimmunities. Nature Genet., 37:478-485, 2005
  • Kawamura K, Yamamura T, Yokoyama K, Chui DH, Fukui Y, Sasazuki T, Inoko H, David CD, Tabira T. HLA-DR2-restricted responses to proteolipid protein 95-116 peptide cause autoimmune encephalitis in transgenic mice. J. Clin. Invest., 105:977-984, 2000
  • Tamai H, Sudo T, Kimura A, Mukuta T, Matsubayashi S, Kuma K, Nagataki S, Sasazuki T. Association between the DRB1*08032 histocompatibility antigen and methimazole-induced agranulocytosis in Japanese patients with Graves Disease. Annals of Internal Medicine, 124: 490-494, 1996
  • Nishimura Y, Kamikawaji N, Fujisawa K, Yoshizumu H, Yasunami M, Kimura A, Sasazuki T. Genetic control of immune response and disease susceptibility by the HLA-DQ gene. Immunol. Rev., 142:459-466, 1991
  • Todd JA, Fukui Y, Kitagawa T, Sasazuki T. The A3 allele of the HLA-DQA1 locus in associated with susceptibility to type 1 diabetes in Japanese. Proc. Natl. Acad. Sci., 87:1094-1098, 1990
  • Honda K, Hirayama K, Kikuchi I, Nagato H, Tamai H, Sasazuki T. HLA and silicosis in Japan. New Engl. J. Med., 319: 1610, 1988
  • Kikuchi I, Ozawa T, Hirayama K, Sasazuki T. An HLA-linked gene controls susceptibility to lepromatous leprosy through T cell regulation.: Leprocy Review 57, suppl. 2.: 139-142, 1986.
  • Sasazuki T, Nishimura Y, Muto M, Ohta N. HLA-linked genes controlling the immune response and disease susceptibility. Immunological Reviews, 70: 51-75, 1983.
  • Uno H, Sasazuki T, Tamai H, Matsumoto H. Two major genes, linked to HLA and Gm, control susceptibility to Graves' disease. Nature, 292: 768-770, 1981.
  • Sasazuki T, Ohta M, Kaneoka R, Kojima S. Association between and HLA haplotype and low responsiveness to schistosomal worm antigen in man. J. Exp. Med., 152: 314s-318s, 1980.
  • Sasazuki T, Hayase R, Iwamoto I, Tsuchida H. HLA and acute postreptococcal glomerulonephritis. New Engl. J. Med., 22: 1184-1185, 1979.
  • Sasazuki T, Kohno Y, Iwamoto I, Kosaka K, Akimoto K, Maruyama H, Ishiba A, Konishi J, Takeba Y, Naito S. HLA and Graves' disease or diabetes mellitus in Japan. New Engl. J. Med., 298: 630-631, 1978.
  • Sasazuki T, McDevitt HO, Grumet FC. The association between genes in the major histocompatibility complex and disease susceptibility. Ann. Rev. Med., 28: 425-452, 1977.
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Ⅲ. HLAによる骨髄移植に於けるGVH病発現機構の解明
  • Morishima S, Kashiwase K, Matsuo K, Azuma F, Yabe T, Sato-Otsubo A, Ogawa S, Shiina T, Satake M, Saji H, Kato S, Kodera Y, Sasazuki T, Morishima Y. High risk HLA alleles for severe acute graft-versus-host disease and mortality in unrelated donor bone marrow transplantation. Haematologica. pii: haematol.2015.136903, 2016
  • Sato-Otsubo A, Nannya Y, Kashiwase K, Onizuka M, Azuma F, Akatsuka Y, Ogino Y, Satake M, Sanada M, Chiba S, Saji H, Inoko H, Kennedy GC, Yamamoto K, Morishima S, Morishima Y, Kodera Y, Sasazuki T, Ogawa S. Genome-wide surveillance of mismatched alleles for graft versus host disease in stem cell transplantation. Blood.. 126(25):2752-63, 2015
  • Morishima Y, Kashiwase K, Matsuo K, Azuma F, Morishima S, Onizuka M, Yabe T, Murata M, Doki N, Eto T, Mori T, Miyamura K, Sao H, Ichinohe T, Saji H, Kato S, Atsuta Y, Kawa K, Kodera Y, Sasazuki T. Biological significance of HLA locus matching in unrelated donor bone marrow transplantation. Blood. 125(7):1189-97, 2015
  • Morishima S, Ogawa S, Matsubara A, Kawase T, Nannya Y, Kashiwase K, Satake M, Saji H, Inoko H, Kato S, Kodera Y, Sasazuki T, Morishima Y; Japan Marrow Donor Program. Impact of highly conserved HLA haplotype on acute graft-versus-host disease. Blood. 115(23):4664-4670. 2010
  • Kawase T, Matsuo K, Kashiwase K, Inoko H, Saji H, Ogawa S, Kato S, Sasazuki T, Kodera Y, Morishima Y. HLA mismatch combinations associated with decreased risk of relapse: Implications for molecular mechanism. Blood., 113(12):2851-8, 2008
  • Kawase T, Morishima Y, Matsuo K, Kashiwase K, Inoko H, Saji H, Kato S, Juji T, Kodera Y, Sasazuki T. High-risk HLA allele mismatch combinations responsible for severe acute graft versus host disease and implication for its molecular mechanism. Blood., 110(7):2235-41, 2007
  • Morishima Y, Sasazuki T, Inoko H, Juji T, Akaza T, Yamamoto K, Ishikawa Y, Kato S, Sao H, Sakamaki H, Kawa K, Hamajima N, Asano S, Kodera Y, for the Japan Marrow Donor Program. The clinical significance of HLA allele compatibility in patients transplanted with marrow from a serologically HLA-A, B and DR matched unrelated donor. Blood., 99: 4200-4206, 2002
  • Sasazuki T, Juji T, Morishima Y, Kinukawa N, Kashiwabara H, Inoko H, Yoshida T, Kimura A, Akaza T, Kamikawaji N, Kodera Y, Takaku F. Effect of matching of class I HLA alleles on clinical outcome after transplantation of hematopoietic stem cells from an unrelated donor. New Engl. J. Med., 339:1177-1185, 1998
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Ⅳ. HLAとペプチドに関する研究
  • Kusano S, Kukimoto-Niino M, Satta Y, Ohsawa N, Uchikubo-Kamo T, Wakiyama M, Ikeda M, Terada T, Yamamoto K, Nishimura Y, Shirouzu M, Sasazuki T, Yokoyama S. Structural basis for the specific recognition of the major antigenic peptide from the Japanese cedar pollen allergen Cry j 1 by HLA-DP5. J Mol Biol. 426(17):3016-27, 2014
  • Sano T, Yamamoto K, Fukui Y, Sasazuki T. Spontaneous clustering of Thy-1 antigens on CD4+ CD8+ thymocytes lacking TCR engagement by MHC/peptide complexes. Eur. J. Immunol 29:403-412, 1999
  • Gyotoku T, Fukui Y, Sasazuki T. An endogenously processed self peptide and the corresponding exogenous peptide bound to the same MHC class II molecule could be distinct ligands for TCR with different kinetic stability. Eur. J. Immunol.,28:4050-4061, 1998
  • Tana T., Kamikawaji,N., Savoie,C.J., Sudo,T., Kinoshita,Y., Sasazuki T. A HLA binding motif-aided peptide epitope library: A novel library design for the screening of HLA-DR4-restricted antigenic peptides recognized by CD4+ T cells. J. Human Genet., 43:14-21,1998
  • Sudo T, Kamikawaji N, Kimura A, Date Y, Savoie CJ, Nakashima H, Furuichi E, Kuhara S, Sasazuki T. Differences in MHC-class I self peptide repertoires among HLA-A2 subtypes. J. Immunol., 155: 4749-4756 1995.
  • Dong RP, Kamikawaji N, Toida N, Fujita Y, Kimura A, Sasazuki T. Characterization of T cell epitopes restricted by HLA-DP9 in streptococcal M12 protein. J. Immunol., 154: 4536-4545, 1995
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Ⅴ. SARSに関する研究
  • Fukushi M, Yoshinaka Y, Matsuoka Y, Hatakeyama S, Ishizaka Y, Kirikae T, Sasazuki T, Miyoshi-Akiyama T. Monitoring of S protein maturation in the endoplasmic reticulum by calnexin is important for the infectivity of severe acute respiratory syndrome coronavirus. J Virol. 86(21):11745-53, 2012
  • Miyoshi-Akiyama T, Ishida I, Fukushi M, Yamaguchi K, Matsuoka Y, Ishihara T, Tsukahara M, Hatakeyama S, Itoh N, Morisawa A, Yoshinaka Y, Yamamoto N, Lianfeng Z, Chuan Q, Kirikae T, Sasazuki T. Fully human monoclonal antibody directed to proteolytic cleavage site in severe acute respiratory syndrome (SARS)coronavirus S protein neutralizes the virus in a rhesus macaque SARS model. J Infect Dis. 203(11):1574-1581, 2011
  • Haga S, Nagata N, Okamura T, Yamamoto N, Sata T, Yamamoto N, Sasazuki T, Ishizaka Y. TACE antagonists blocking ACE2 shedding caused by the spike protein of SARS-CoV are candidate antiviral compounds. Antiviral Res. 85(3):551-555, 2010
  • Keicho N, Itoyama S, Kashiwase K, Phi NC, Long HT, Ha le D, Van Ban V, Hoa BK, Hang NT, Hijikata M, Sakurada S, Satake M, Tokunaga K, Sasazuki T, Quy T. Association of human leukocyte antigen class Ⅱ alleles with severe acute respiratory syndrome in the Vietnamese population. Hum Immunol. 70(7):527-531, 2009
  • Haga S, Yamamoto N, Nakai-Murakami C, Osawa Y, Tokunaga K, Sata T, Yamamoto N, Sasazuki T, Ishizaka Y. Modulation of TNF-α-converting enzyme by the spike protein of SARS-CoV and ACE2 induces TNF-α production and facilitates viral entry. Proc Natl Acad Sci USA,, 105(22):7809-7814, 2008
  • Nishiyama A, Wakasugi N, Kirikae T, Quy T, Ha le D, Ban VV, Long HT, Keicho N, Sasazuki T, Kuratsuji T. Risk factors for SARS infection within hospitals in Hanoi, Vietnam. Jpn J Infect Dis. 61(5):388-90, 2008
  • Hatakeyama S, Matsuoka Y, Ueshiba H, Komatsu N, Itoh K, Shichijo S, Kanai T, Fukushi M, Ishida I, Kirikae T, Sasazuki T, Miyoshi-Akiyama T. Dissection and identification of regions required to form pseudoparticles by the interaction between the nucleocapsid (N)and membrane (M)proteins of SARS coronavirus. Virology, 380(1):99-108, 2008
  • Itoyama S, Keicho N, Hijikata M, Quy T, Phi NC, Long HT, Ha le D, Ban VV, Matsushita I, Yanai H, Kirikae F, Kirikae T, Kuratsuji T, Sasazuki T. Identification of an alternative 5'-untranslated exon and new polymorphisms of angiotensin-converting enzyme 2 gene: lack of association with SARS in the Vietnamese population. Am. J. Med. Genet., 136(1):52-57, 2005
  • Nishiura H, Kuratsuji T, Quy T, Phi NC, Van Ban V, Ha LE, Long HT, Yanai H, Keicho N, Kirikae T, Sasazuki T, Anderson RM. Rapid awareness and transmission of severe acute respiratory syndrome in Hanoi French Hospital, Vietnam. Am. J. Trop. Med. Hyg., 73(1):17-25. 2005
  • Hamano E, Hijikata M, Itoyama S, Quy T, Phi NC, Long HT, Ha le D, Ban VV, Matsushita I, Yanai H, Kirikae F, Kirikae T, Kuratsuji T, Sasazuki T, Keicho N. Polymorphisms of interferon-inducible genes OAS-1 and MxA associated with SARS in the Vietnamese population. Biochem Biophys Res Commun. 329(4):1234-1239, 2005
  • Shichijo S, Keicho N, Long HT, Quy T, Phi NC, Ha LD, Ban VV, Itoyama S, Hu CJ, Komatsu N, Kirikae T, Kirikae F, Shirasawa S, Kaji M, Fukuda T, Sata M, Kuratsuji T, Itoh K, Sasazuki T. sAssessment of synthetic peptides of severe acute respiratory syndrome coronavirus recognized by long-lasting immunity. Tissue Antigens,, 64(5):600-7, 2004
  • Itoyama S, Keicho N, Quy T, Phi NC, Long HT, Ha le D, Ban VV, Ohashi J, Hijikata M, Matsushita I, Kawana A, Yanai H, Kirikae T, Kuratsuji T, Sasazuki T. ACE1 polymorphism and progression of SARS. Biochem Biophys Res Commun., 323(3):1124-9, 2004
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Ⅵ. 非免疫関連疾病の遺伝解析
  • Ishii E, Ueda I, Shirakawa R, Yamamoto K, Horiuchi H, Ohga S, Furuno K, Morimoto A, Imayoshi M, Ogata Y, Zaitzu M, Sako M, Koike K, Sakata A, Takada H, Hara T, Imashuku S, Sasazuki T, Yasukawa M. Genetic subtypes of familial hemophagocytic lymphohistiocytosis: correlations with clinical features and cytotoxic T lymphocyte/natural killer cell functions. Blood, 105(9):3442-8, 2005
  • Shirasawa S, Sugiyama S, Baba I, Inokuchi J, Sekine S, Ogino K, Kawamura Y, Dohi T, Fujimoto M, Sasazuki T. Dermatitis due to epiregulin deficiency and a critical role of epiregulin in immune-related responses of keratinocyte and macrophage. Proc Natl Acad Sci U S A.,, 101(38):13921-6, 2004
  • Yamamoto K, Ishii E, Sako M, Ohga S, Furuno K, Suzuki N, Ueda I, Imayoshi M, Yamamoto S, Morimoto A, Takada H, Hara T, Imashuku S, Sasazuki T, Yasukawa M. Identification of novel MUNC13-4 mutations in familial haemophagocytic lymphohistiocytosis and functional analysis of MUNC13-4-deficient cytotoxic T lymphocytes. J Med Genet., 41(10):763-7, 2004
  • Shirasawa S, Arata A, Onimaru H, Roth K, Brown G, Horning S, Arata S, Okumura K, Sasazuki T and Korsmeyer S. Rnx-deficiency results in congenital central hypoventilation. Nature Genetics, 24:287-290, 2000
  • Kimura A, Harada H, Park JE, Nishi H, Satoh M, Takahashi M, Hiroi S, Sasaoka T, Ohbuchi N, Nakamura T, Koyanagi T, Hwang TH, Choo JA, Chung KS, Hasegawa A., Nagai R, Okazaki O, Nakamura H, Matsuzaki M, Sakamoto T, Toshima H., Koga Y, Imaizumi T, Sasazuki T. Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy. Nature Genet., 16: 379-382, 1997.
  • Urabe K, Kimura A, Harada F, Iwanaga T, Sasazuki T. Gene conversion in steroid 21-hydroxylase genes. Am. J. Human Genet., 46:1178-1186, 1990
  • Harada F, Kimura A, Iwanaga T, Shimozawa K, Yata J, Sasazuki T. Gene conversion-like events cause steroid 21-hydroxylase deficiency in congenital adrenal hyperplasia. Proc. Natl. Acad. Sci. USA., 84: 8091-8094, 1987
  • Harada F, Sada M, Kamiya T, Yanase Y, Kawasaki T, Sasazuki T. Genetic analysis of Kawasaki syndrome. Am. J. Human Genet., 4: 537-538, 1986
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Ⅶ. 糖尿病に関する研究
  • Noto H, Tsujimoto T, Sasazuki T, Noda M. Significantly increased risk of cancer in patients with diabetes mellitus: a systematic review and meta-analysis. Endocr Pract. 17(4):616-628. 2011.
  • Noto H, Osame K, Sasazuki T, Noda M. Substantially increased risk of cancer in patients with diabetes mellitus: a systematic review and meta-analysis of epidemiologic evidence in Japan. J Diabetes Complications. 24(5):345-353, 2010
  • Fujimoto T, Miyasaka K, Koyanagi M, Tsunoda T, Baba I, Doi K, Ohta M, Kato N, Sasazuki T, Shirasawa S. Altered energy homeostasis and resistance to diet-induced obesity in KRAP-deficient mice. PLoS ONE. 4(1):e4240, 2009
  • Takeuchi F, Ochiai Y, Serizawa M, Yanai K, Kuzuya N, Kajio H, Honjo S, Takeda N, Kaburagi Y, Yasuda K, Shirasawa S, Sasazuki T, Kato N. Search for type 2 diabetes susceptibility genes on chromosomes 1q, 3q and 12q. J. Hum. Genet., 53(4):314-24, 2008
  • Takeuchi F, Yanai K, Inomata H, Kuzuya N, Kajio H, Honjo S, Takeda N, Kaburagi Y, Yasuda K, Shirasawa S, Sasazuki T, Kato N. Search of type 2 diabetes susceptibility gene on chromosome 20q. Biochem Biophys Res Commun. 357(4):1100-6, 2007
  • Nawata H, Shirasawa S, Nakashima N, Araki E, Hashiguchi J, Miyake S, Yamauchi T, Hamaguchi K, Yoshimatsu H, Takeda H, Fukushima H, Sasahara T, Yamaguchi K, Sonoda N, Sonoda T, Matsumoto M, Tanaka Y, Sugimoto H, Tsubouchi H, Inoguchi T, Yanase T, Wake N, Narazaki K, Eto T, Umeda F, Nakazaki M, Ono J, Asano T, Ito Y, Akazawa S, Hazegawa I, Takasu N, Shinohara M, Nishikawa T, Nagafuchi S, Okeda T, Eguchi K, Iwase M, Ishikawa M, Aoki M, Keicho N, Kato N, Yasuda K, Yamamoto K, Sasazuki T. Genome-wide linkage analysis of type 2 diabetes mellitus reconfirms the susceptibility locus on 11p13-p12 in Japanese. J Hum Genet., 49(11):629-34, 2004
  • Kaburagi Y, Yamashita R, Ito Y, Okochi H, Yamamoto-Honda R, Yasuda K, Sekihara H, Sasazuki T, Kadowaki T, Yazaki Y. Insulin-induced cell cycle progression is impaired in chinese hamster ovary cells overexpressing insulin receptor substrate-3. Endocrinology, 145(12):5862-74, 2004
  • Kaburagi Y, Satoh S, Yamamoto-Honda R, Ito Y, Akanuma Y, Sekihara H, Yasuda K, Sasazuki T, Kadowaki T, Yazaki Y. Protection of insulin receptor substrate-3 from staurosporine-induced apoptosis. Biochemical & Biophysical Research Communications,300(2):371-7, 2003
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Ⅷ. 発がんの遺伝子解析
  • Goulielmaki M, Koustas E, Moysidou E, Vlassi M, Sasazuki T, Shirasawa S, Zografos G, Oikonomou E, Pintzas A. BRAF associated autophagy exploitation: BRAF and autophagy inhibitors synergise to efficiently overcome resistance of BRAF mutant colorectal cancer cells. Oncotarget. doi: 10.18632/oncotarget.6942, 2016
  • Dunne PD, Dasgupta S, Blayney J, McArt DG, Redmond KL, Weir JA, Bradley CA, Sasazuki T, Shirasawa S, Wang T, Srivastava S, Ong CW, Arthur K, Salto-Tellez M, Wilson RH, Johnston PG, Van Schaeybroeck S. EphA2 expression is a key driver of migration and invasion and a poor prognostic marker in colorectal cancer. Clin Cancer Res. 22(1):230-42, 2016
  • Yoo BH, Zagryazhskaya A, Li Y, Koomson A, Khan IA, Sasazuki T, Shirasawa S, V Rosen K. Upregulation of ATG3 contributes to autophagy induced by the detachment of intestinal epithelial cells from the extracellular matrix, but promotes autophagy-independent apoptosis of the attached cells. Autophagy.11(8):1230-46, 2015
  • Iwamoto M, Kawada K, Nakamoto Y, Itatani Y, Inamoto S, Toda K, Kimura H, Sasazuki T, Shirasawa S, Okuyama H, Inoue M, Hasegawa S, Togashi K, Sakai Y. Regulation of 18F-FDG accumulation in colorectal cancer cells with mutated KRAS. J Nucl Med. 55(12):2038-44, 2014
  • Sun Q, Luo T, Ren Y, Florey O, Shirasawa S, Sasazuki T, Robinson DN, Overholtzer M. Competition between human cells by entosis. Cell Res. 24(11):1299-310, 2014
  • Van Schaeybroeck S, Kalimutho M, Dunne PD, Carson R, Allen W, Jithesh PV, Redmond KL, Sasazuki T, Shirasawa S, Blayney J, Michieli P, Fenning C, Lenz HJ, Lawler M, Longley DB, Johnston PG.ADAM17-dependent c-MET-STAT3 signaling mediates resistance to MEK inhibitors in KRAS mutant colorectal cancer. Cell Res. 7(6):1940-55, 2014
  • Organ SL, Hai J, Radulovich N, Marshall CB, Leung L, Sasazuki T, Shirasawa S, Zhu CQ, Navab R, Ikura M, Tsao MS.p120RasGAP is a mediator of rho pathway activation and tumorigenicity in the DLD1 colorectal cancer cell line. PLoS One. 9(1):e86103, 2014
  • Vartanian S, Bentley C, Brauer MJ, Li L, Shirasawa S, Sasazuki T, Kim JS, Haverty P, Stawiski E, Modrusan Z, Waldman T, Stokoe D. Identification of mutant K-Ras-dependent phenotypes using a panel of isogenic cell lines. J Biol Chem. 288(4):2403-13, 2013
  • Ikonomou G, Kostourou V, Shirasawa S, Sasazuki T, Samiotaki M, Panayotou G. Interplay between oncogenic K-Ras and wild-type H-Ras in Caco2 cell transformation. J Proteomics. 75(17):5356-69, 2012
  • Gulhati P, Zaytseva YY, Valentino JD, Stevens PD, Kim JT, Sasazuki T, Shirasawa S, Lee EY, Weiss HL, Dong J, Gao T, Evers BM. Sorafenib enhances the therapeutic efficacy of rapamycin in colorectal cancers harboring oncogenic KRAS and PIK3CA. Carcinogenesis. 33(9):1782-90, 2012
  • Yuen HF, Abramczyk O, Montgomery G, Chan KK, Huang YH, Sasazuki T, Shirasawa S, Gopesh S, Chan KW, Fennell D, Janne P, El-Tanani M, Murray JT. Impact of oncogenic driver mutations on feedback between the PI3K and MEK pathways in cancer cells. Biosci Rep. 32(4):413-22, 2012
  • Di Nicolantonio F, Arena S, Tabernero J, Grosso S, Molinari F, Macarulla T, Russo M, Cancelliere C, Zecchin D, Mazzucchelli L, Sasazuki T, Shirasawa S, Geuna M, Frattini M, Baselga J, Gallicchio M, Biffo S, Bardelli A. Deregulation of the PI3K and KRAS signaling pathways in human cancer cells determines their response to everolimus. J Clin Invest. 120(8):2858-2866, 2010
  • Shahrzad S, Shirasawa S, Sasazuki T, Rak JW, Coomber BL. Low-dose metronomic cyclophosphamide treatment mediates ischemia-dependent K-ras mutation in colorectal carcinoma xenografts. Oncogene, 27(26):3729-38, 2008
  • Fujimoto T, Koyanagi M, Baba I, Nakabayashi K, Kato N, Sasazuki T, Shirasawa S. Analysis of KRAP expression and localization, and genes regulated by KRAP in a human colon cancer cell line. J Hum Genet., 52(12):978-84, 2007
  • Ries S, Biederer C, Woods D, Shifman O, Shirasawa S, Sasazuki T, McMahon M, Oren M, McCormick F. Opposing effects of Ras on p53: Transcriptional Activation of mdm2 and induction of p19ARF. Cell, 103: 321-330, 2000
  • Baba I, Shirasawa S, Iwamoto R, Okumura K, Tsunoda T, Nishioka M, Fukuyama K, Yamamoto K, Mekada E, Sasazuki T. Involvement of deregulated epiregulin expression in tumorigenesis in vivo through activated Ki-ras signaling pathway in human colon cancer cells. Cancer Res., 60:6886-6889, 2000
  • Shirasawa S, Furuse M, Yokoyama N, Sasazuki T. Altered growth of human colon cancer cell lines disrupted at activated Ki-ras. Science, 260: 85-88, 1993
  • Nagase H, Miyoshi Y, Horii A, Aoki T, Ogawa M, Utsunomiya J, Baba S, Sasazuki T, Nakamura Y. Correlation between the location of germ-line mutations in the APC gene and the number of colorectal polyps in familial adenomatous polyposis patients. Cancer Research, 52:4055-4057, 1992
  • Sugio K, Ishida T, Yokoyama H, Inoue T, Sugimachi K, Sasazuki T. ras gene mutations as a prognostic marker in adenocarcinoma of the human lung without lymph node metastasis. Cancer Research, 52:2903-2906, 1992
  • Shirasawa S, Urabe K, Yanagawa Y, Toshitani K, Iwama T, Sasazuki T. p53 gene mutations in colorectal tumors from patients with familial polyposis coli. Cancer Res., 51:2874-2878, 1991
  • Sasaki M, Okamoto M, Sato C, Sugio K, Soejima J, Iwama T, Ikeuchi T, Tonomura A, Miyaki M, Sasazuki T. Loss of constitutional heterozygosity in colorectal tumors from patients with familial polyposis coli and those with non-polyposis colorectal carcinoma. Cancer Res.,49:4402-4406, 1989
  • Okamoto N, Sasaki M, Sugio K, Sato C, Iwama T, Ikeuchi T, Tonomura A, Sasazuki T, Miyaki M. Loss of constitutional heterozygosity in colon carcinoma from patients with familial polyposis coli. Nature (Lond.)331:273-277: 1988
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Ⅸ. ハプトグロビンとヘモグロビンに関する研究
  • Tsunoo H, Sasazuki T, Sato H, Nakajima H. Effect of haptoglobin on immunological activity of hemoglobin. Immunochemistry, 11:673,1974.
  • Sasazuki T, Tsunoo H, Nakajima H. Interaction of human hemoblobin with haptoglobin or antihemoglobin antibody. J. Biol. Chem., 249(8): 2441, 1974.
  • Sasazuki T, Isomoto A, Nakajima H. Circular dichroism and absorption spectra of hemoglobin bart's. J. Mol. Biol., 65:365, 1972
  • Sasazuki T. Immunochemical and physicochemical properties of haptoglobin, antihemoglobin antibody, and their complexes with hemoglobin. Immunochemistry, 8(8), 695, 1971.
  • Sasazuki T. Studies on haptoglobin Ⅰ. Immunochemical properties of haptoglobin and antihemoglobin antibody Ⅰ. Proc. Jap. Acad., 46: 820-825, 1970.
  • Hamaguchi H, Sasazuki T. Control of haptoglobin metabolism Ⅲ. Purification of the hemoglobin-haptoglobin subunit and the hemoglobin-haptoglobin complex of human haptoglobin 1-1 type. Proc. Jap. Acad., 43: 332-337, 1967.
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