Education

Honors & Awards

• 1978: Young Investigator Award, the Japanese Biomedical Society
• 1981: Noguchi Hideyo-Memorial Award for Medicine
• 1981: Asahi Prize
• 1984: Osaka Science Prize 
• 1984: Kihara Prize (Japanese Genetics Society)
• 1985: Erwin von Baelz Prize
• 1988: American Association of Immunologists (Honorary Member)
• 1988: Takeda Medical Prize
• 1991-1996: Fogarty Scholar-in-residence at NIH
• 1992: Boehring-Kitasato Prize
• 1994: Uehara Prize
• 1996: The Imperial Prize and the Japan Academy Prize
• 2000: Award “Person of Cultural Merit” by the Japanese Government
• 2001: Foreign Associate of U.S. National Academy of Sciences
• 2003: Member of Leopoldina (The German Academy of Natural Scientists)
• 2005: Member of the Japan Academy
• 2012: Robert Koch Prize
• 2013: Order of Culture
• 2014: Tang Prize, Biopharmaceutical Science Award
• 2014: William B. Coley Award, Cancer Research Institute
• 2014: 4th JCA-CHAOO Award, Japanese Cancer Association
• 2015: Richard V. Smalley, MD Memorial Award, Society for Immunotherapy of Cancer
• 2016: Kyoto Prize
• 2016: The Keio Medical Science Prize
• 2016: Thomson Reuters Citation Laureate, Physiology or Medicine
• 2016: Fudan-Zhongzhi Science Award in Biomedicine
• 2017: Warren Alpert Foundation Prize
• 2018: JMA Supreme Award of Merit
• 2018: The Nobel Prize in Physiology or Medicine
• 2018: Special Honor Award (Kyoto Prefecture)
• 2018: Honorary Citizen (Toyama City)
• 2018: Honor Award (Ube City)
• 2018: Honorary Citizen (Kyoto City)
• 2018: Special Honor Award (Toyama Prefecture)
• 2019: Fellow of the AACR Academy in 2019
• 2019: Honorary Citizen (Kobe City)
• 2019: Prefectural Honor Award (Yamaguchi Prefecture)
• 2019: Prefectural Honor Award (Shizuoka Prefecture) 
• 2019: Academician of Honor of the Spanish Royal Academy of Medicine
• 2019: Honorary Member of The Physiological Society
• 2022: Honorary Academician of Academia Sinica, 2022

Memberships (selection)

• Honorary Member, Japanese Society for Immunology (President 1999-2000)
• Congress of Biochemistry and Molecular Biology (President in 2006)
• Honorary Member, Japanese Society of Interferon & Cytokine Research
• The Japanese Association of Medical Sciences (Vice-President of the 29th General Assembly of the Japanese Association of Medical Sciences)
• Japanese Honorary Member, Japanese Cancer Association
• Honorary Member, The Pharmaceutical Society of Japan

Selected Publications

List of all publications

Studies on immunoglobulin genes and antibody class switching

Honjo, T. and Kataoka, T. Organization of immunoglobulin heavy chain genes and allelic deletion model. Proc. Natl. Acad. Sci. USA 75 2140-2144 (1978)

Honjo, T., Obata, M., Yamawaki-Kataoka, Y., Kataoka, T., Kawakami, T., Takahashi, N. and Mano, Y. Cloning and complete nucleotide sequence of mouse imunoglobulin g1 chain gene. Cell 18 559-568 (1979)

Kataoka, T., Kawakami, T., Takahashi, N. and Honjo, T. Rearrangement of immunoglobulin g1-chain gene and mechanism for heavy-chain class switch. Proc. Natl. Acad. Sci. USA 77 919-923 (1980)

Yaoita, Y. and Honjo, T. Deletion of immunoglobulin heavy chain genes from expressed allelic chromosome. Nature 286 850-853 (1980)

Kataoka, T., Miyata, T. and Honjo, T. Repetitive sequences in class-switch recombination regions of immunoglobulin heavy chain genes. Cell 23 357-368 (1981)

Nikaido, T., Nakai, S. and Honjo, T. Switch region of the immunoglobulin Cg gene is composed of simple tandem repetitive sequences. Nature 292 845-848 (1981)

Shimizu, A., Takahashi, N., Yamawaki-Kataoka, Y., Nishida, Y., Kataoka, T. and Honjo, T. Ordering of mouse immunoglobulin heavy chain genes by molecular cloning. Nature 289 149-153 (1981)

Shimizu, A., Takahashi, N., Yaoita, Y. and Honjo, T. Organization of the constant-region gene family of the mouse immunoglobulin heavy chain. Cell 28 499-506 (1982)

Noma, Y., Sideras, P., Naito, T., Bergstedt-Lindquist, S., Azuma, C., Severinson, E., Tanabe, T., Kinashi, T., Matsuda, F., Yaoita, Y. and Honjo, T. Cloning of cDNA encoding the murine IgG1 induction factor by a novel strategy using SP6 promoter. Nature 319 640-646 (1986)

Kinashi, T., Harada, N., Severinson, E., Tanabe, T., Sideras, P., Konishi, M., Azuma, C., Tominaga, A., Bergstedt-Lindquist, S., Takahashi, M., Matsuda, F., Yaoita, Y., Takatsu, K. and Honjo. T. Cloning of complementary DNA encoding T-cell replacing factor and identity with B-cell growth factor II. Nature 324 70-73 (1986)

Iwasato, T., Shimizu, A., Honjo, T. and Yamagishi, H. Circular DNA is excised by immunoglobulin class switch recombination. Cell 62 143-149 (1990)

Tashiro, K., Tada, H., Heilker, R., Shirozu, M., Nakano, T. and Honjo, T. Signal sequence trap: cloning strategy for secreted proteins and type I membrane proteins. Science 261 600-603 (1993)

Matsuda, F., Ishii, K., Bourvagnet, P., Kuma, K., Hayashida, H., Miyata, T. and Honjo, T. The complete nucleotide sequence of the human immunoglobulin heavy chain variable region locus. J. Exp. Med. 188 2151-2162 (1998)

Kinoshita, K., Tashiro, J., Tomita, S., Lee, C-G. and Honjo, T. Target specificity of immunoglobulin class switch recombination is not determined by nucleotide sequences of S regions. Immunity 9 849-858 (1998)

Muramatsu, M., Sankaranand, V. S., Anant, S., Sugai, M., Kinoshita, K., Davidson, N. O. and Honjo, T. Specific expression of activation-induced cytidine deaminase (AID), a novel member of the RNA editing deaminase family in germinal center B cells. J. Biol. Chem. 274 18470-18476 (1999)

Muramatsu, M., Kinoshita, K., Fagarasan, S., Yamada, S., Shinkai, Y. and Honjo, T. Class switch recombination and hypermutation require activation- induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 102 553-563 (2000)

Revy, P., Muto, T., Levy, Y., Geissmann, F., Plebani, A., Sanal, O., Catalan, N., Forveille, M., D.-Lagelouse, R., Gennery, A., Tezcan, I., Ersoy, F., Kayserili, H., Ugazio, A.G., Brousse, N., Muramatsu, M., Notarangelo, L.D., Kinoshita, K., Honjo, T., Fischer, A. and Durandy, A. Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the hyper-IgM syndrome (HIGM2). Cell 102 565-575 (2000)

Petersen, S., Casellas, R., Reina-S-M, B., Chen, H., Difilippantonio, M., Wilson, P., Hanitsch, L., Celeste, A., Muramatsu, M., Pilch, D., Redon, C., Ried, T., Bonner, W., Honjo, T., Nussenzweig, M. and Nussenzweig, A. AID is required to initiate Nbs 1/??H2AX focus formation and mutations at sites of class switching. Nature 414 660-665 (2001)

Fagarasan, S., Kinoshita, K., Muramatsu, M., Ikuta, K. and Honjo, T. In situ class switching and differentiation to IgA-producing cells in the gut lamina propria. Nature 413 639-643 (2001)

Chen, X., Kinoshita, K. and Honjo, T. Variable deletion and duplication at recombination junction ends: implication for staggered double-strand cleavage in class switch recombination. Proc. Natl. Acad. Sci. USA 98 13860-13865 (2001)

Okazaki, I., Kinoshita, K., Muramatsu, M., Yoshikawa, K. and Honjo, T. The AID enzyme induces class switch recombination in fibroblasts. Nature 416 340-345 (2002)

Yoshikawa, K., Okazaki, I., Eto, T., Kinoshita, K., Muramatsu, M., Nagaoka, H. and Honjo, T. The AID enzyme induces hypermutation in an actively transcribed gene in fibroblasts. Science 296 2033-2036 (2002)

Okazaki, I., Hiai, H., Kakazu, N., Yamada, S., Muramatsu, M., Kinoshita, K. and Honjo, T. Constitutive expression of AID leads to tumorigenesis. J. Exp. Med. 197 1173-1181 (2003)

Ta, V-T., Nagaoka, H., Catalan, N., Durandy, A., Fischer, A., Imai, K., Nonoyama, S., Tashiro, J., Ikegawa, M., Ito, S., Kinoshita, K., Muramatsu, M. and Honjo, T. AID mutant analyses indicate requirement for class-switch-specific cofactors. Nature Immunol. 4 843-848 (2003)

Begum, N. A., Kinoshita, K., Kakazu, N., Muramatsu, M., Nagaoka, H., Shinkura, R., Biniszkiewicz, D., Boyer, L. A., Jaenisch, R. and Honjo, T. Uracil DNA glycosylase activity is dispensable for immunoglobulin class switch. Science 305 1160-1163 (2004)

Kobayashi M, Aida M, Nagaoka H, Begum NA, Kitawaki Y, Nakata M, Stanlie A, Doi T, Kato L, Okazaki IM, Shinkura R, Muramatsu M, Kinoshita K, Honjo T. AID-induced decrease in topoisomerase 1 induces DNA structural alteration and DNA cleavage for class switch recombination. Proc Natl Acad Sci U S A. 106:22375-80 (2009)

Stanlie A, Aida M, Muramatsu M, Honjo T, Begum NA. Histone3 lysine4 trimethylation regulated by the facilitates chromatin transcription complex is critical for DNA cleavage in class switch recombination. Proc Natl Acad Sci U S A. 107:22190-5 (2010)

Wei M, Shinkura R, Doi Y, Maruya M, Fagarasan S, Honjo T. Mice carrying a knock-in mutation of Aicda resulting in a defect in somatic hypermutation have impaired gut homeostasis and compromised mucosal defense. Nat Immunol. 12:264-70 (2011)

Honjo T, Kobayashi M, Begum N, Kotani A, Sabouri S, Nagaoka H. The AID dilemma: infection, or cancer? Adv Cancer Res. 113:1-44 (2012)

Kato L, Begum NA, Burroughs AM, Doi T, Kawai J, Daub CO, Kawaguchi T, Matsuda F, Hayashizaki Y, Honjo T. Nonimmunoglobulin target loci of activation-induced cytidine deaminase (AID) share unique features with immunoglobulin genes. Proc Natl Acad Sci U S A. 109 :2479-84 (2012)

Stanlie A, Yousif AS, Akiyama H, Honjo T, Begum NA. Chromatin reader Brd4 functions in Ig class switching as a repair complex adaptor of nonhomologous end-joining. Mol Cell 55:97-110 (2014)

Hu W, Begum NA, Mondal S, Stanlie A, Honjo T. Identification of DNA cleavage- and recombination-specific hnRNP cofactors for activation-induced cytidine deaminase. Proc Natl Acad Sci U S A. 112:5791-6 (2015)

Husain,A., Begum, NA., Taniguchi, T., Taniguchi, H., Kobayashi, M. and Honjo, T. Chromatin remodeller SMARCA4 recruits topoisomerase 1 and suppresses transcription-associated genomic instability. Nature Communications 7, Article number:10549. doi:10.1038/ncomms10549

Studies on immune-inhibitory receptor PD-1

Ishida, Y., Agata, Y., Shibahara, K. and Honjo, T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 11 3887-3895 (1992)

Nishimura, H., Nose, M., Hiai, H., Minato, N. and Honjo, T. Development of lupus-like autoimmune disease by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 11 141-151 (1999)

Freeman, G. J., Long, A. J., Iwai, Y., Bourque, K., Chernova, T., Nishimura, H., Fitsz, L. J., Malenkovich, N., Okazaki, T., Byrne, M. C., Horton, H. F., Fouser, L., Carter, L., Ling, V., Bowman, M. R., Carreno, B. M., Collins, M., Wood, C. R. and Honjo, T. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J. Exp. Med. 192 1027-1034 (2000)

Latchman, Y., Wood, C., Chernova, T., Borde, M., Chernova, I., Iwai, Y., Malenkovich, N., Long, A., Bourque, K., Boussiotis, V., Nishimura, H., Honjo, T., Sharpe, A. and Freeman, G. PD-L2, a novel B7 homologue, is a second ligand for PD-1 and inhibits T cell activation. Nature Immunol. 2 261-268 (2001)

Nishimura, H., Tanaka, Y., Okazaki, T., Nakatani, K., Hara, M., Matsumori, A., Sasayama, S., Hiai, H., Minato, N. and Honjo, T. Autoimmune dilated cardiomyopathy in PD-1 receptor deficient mice. Science 291 319-322 (2001)

Iwai, Y., Shida, M., Tanaka, Y., Okazaki, T., Honjo, T. and Minato, N. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc. Natl. Acad. Sci. USA 99 12293-12297 (2002)

Okazaki, T., Tanaka, Y., Nishio, R., Mitsuie, T., Mizoguchi, A., Jian, W., Ishida, M., Matsumori, A., Minato,. N. and Honjo, T. Autoantibodies against cardiac troponin I are responsible for the dilated cardiomyopathy in PD-1 deficient mice. Nature Medicine 9 1477-1483 (2003)

Okazaki, T. and Honjo, T. Rejuvenating exhausted T cells during chronic viral infection. Cell. 124(3):459-61 (2006)

Hamanishi, J., Mandai, M., Iwasaki, M., Okazaki, T., Tanaka, Y., Yamaguchi, K., Higuchi, T., Yagi, H., Takakura, K., Minato, N., Honjo, T. and Fujii, S. Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. PNAS. 104(9):3360-5 (2007)

Chikuma, S., Suita, N., Okazaki, IM., Shibayama, S. and Honjo, T. TRIM28 prevents autoinflammatory T cell development in vivo. Nat Immunol. 13(6):596-603 (2012)

Okazaki, T., Chikuma, S., Iwai, Y., Fagarasan, S. and Honjo, T. A rheostat for immune responses: the unique properties of PD-1 and their advantages for clinical application. Nat Immunol. 14(12):1212-8 Review (2013)

Studies on cell differentiation by Notch target genes RBP-J

Matsunami, N., Hamaguchi, Y., Yamamoto, Y., Kuze, K., Kangawa, K., Matsuo, H., Kawaichi M. and Honjo, T. A protein binding to the Jk recombination sequence of immunoglobulin genes contains a sequence related to the integrase motif. Nature 342 934-937 (1989)

Furukawa, T., Maruyama, S., Kawaichi, M. and Honjo, T. The Drosophila homolog of the immunoglobulin recombination signal-binding protein regulates peripheral nervous system development. Cell 69 1191-1197 (1992)

Zimber-Strobl, U., Strol, L. J., Meitinger, C., Hinrichs, R.,Sakai, T., Furukawa, T., Honjo, T. and Bornkamm. G. W. Epstein-Barr virus nuclear antigen 2 exerts its transactivating function through interaction with recombination signal binding protein RBP-Jk, the homologue of Drosophila Suppressor of Hairless. EMBO. J. 13 4973-4982 (1994)

Tamura, K., Taniguchi, Y., Minoguchi, S., Sakai, T., Tin Tun, Furukawa, T. and Honjo, T. Physical interaction between a novel domain of the receptor notch and the transcription factor RBP-Jk/Su(H). Curr. Biol. 5 1416-1423 (1995)

Oka, C., Nakano, T., Wakeham, A., Mori, C., Sakai, T., Okazaki, S., Kawaichi, M., Shiota, K., Mak, T. and Honjo, T. Disruption of the mouse RBP-Jk gene results in early embryonic death. Development 121 3291-3301 (1995)

Kato, H., Taniguchi, Y., Kurooka, H., Minoguchi, S., Sakai, T., Nomura-Okazaki, S., Tamura, K. and Honjo, T. Involvement of RBP-J in biological functions of mouse Notch 1 and its derivatives. Development 124 4133-4141 (1997)

Apelqviist, A., Li, H., Sommer, L., Beatus, P., Anderson, D. J., Honjo, T., de Hrabe, M. H., Lendahl, U. and Edlund, H. Notch-signalling controls pancreatic cell differentiation. Nature 400 877-881 (1999)

Tanigaki, K., Han, H., Yamamoto, N., Tashiro, K., Ikegawa, M., Kuroda, K. and Honjo, T. Notch / RBP-J signaling is involved in cell fate determination of marginal zone B cells. Nature Immunol. 3 443-450 (2002)

Kuroda, K., Han, H., Tani, S., Tanigaki, K., Tin Tun, Furukawa, T., Taniguchi, Y., Kurooka, H., Hamada, Y., Toyokuni, S. and Honjo, T. Regulation of marginal zone B cell development by MINT, a suppressor of Notch/RBP-J signaling pathway. Immunity 18 1-20 (2003)

Tanigaki, K., Tsuji, M., Yamamoto, N., Han, H., Tsukada, J., Inoue, H., Kubo, M and Honjo, T. Regulation of ab gd T cell lineage commitment and peripheral T cell response by Notch/RBP-J signaling. Immunity 20 611-622 (2004)

Amsen, D., Blander, J. M., Lee, G. R., Tanigaki, K., Honjo, T. and Flavell, R. A. Instruction of distinct CD4 T helper cell fates by different Notch ligands on antigen-presenting cells. Cell 117 515-526 (2004)

Studies on isolation of IL-2 receptor alpha chain

Nikaido, T., Shimizu, A., Ishida, N., Sabe, H., Teshigawara, K., Maeda, M., Uchiyama, T., Yodoi, J. and Honjo, T. Molecular cloning of cDNA encoding human interleukin-2 receptor. Nature 311 631-635 (1984)

Kondo, S., Shimizu, A., Maeda, M., Tagaya, Y., Yodoi, J. and Honjo, T. Expression of functional human interleukin 2 receptor in mouse T cells by cDNA transfection. Nature 320 75-77 (1986)

Kondo, S., Kinoshita, M., Shimizu, A., Saito, Y., Konishi, M., Sabe, H. and Honjo, T. Expression and functional characterization of artificial mutants of interleukin-2 receptor. Nature 327 64-67 (1987)

Nishi, M., Ishida, Y. and Honjo, T. Expression of functional interleukin-2 receptors in human light chain/Tac transgenic mice. Nature 331 267-269 (1988)