MembersMembers and Laboratories

My Research

I am known for my discovery of activation-induced cytidine deaminase (AID), an enzyme that is essential for class switch recombination and somatic hypermutation of the immunoglobulin genes. The research into the B cell biology began with identification of excised DNA pieces on DNA in IgG or IgA expressing B cells, which helped establishing the basic conceptual framework for the class switch recombination. We identified a series of key molecules involved in immune regulation, including IL-4, IL-5, SDF-1, and IL-2R α chain.

We made significant contribution also to the developmental biology by identification of RBP-J as the Notch signaling target.

I discovered PD-1 (program cell death 1), a negative coreceptor expressed on activated T cells and controlling the effector phase of immune responses. Our research demonstrated that PD-1 inhibition enhanced anti-tumor responses, leading me to propose its application for the treatment of cancers.

Curriculum Vitae

Name: Tasuku Honjo
Place and Date of Birth: Kyoto, Japan on January 27, 1942

Academic Background

1975
Acquired Ph.D. at Kyoto University
1967-1971
Graduate School of Medicine, Kyoto University
1966-1967
Internship, Kyoto University Hospital
1962-1966
Medical Course, Faculty of Medicine, Kyoto University (Acquired M.D. in 1966)
1960-1962
Premedical Course, Faculty of Medicine, Kyoto University

Professional Background

2020-
Director, Center for Cancer Immunotherapy and Immunobiology, Graduate School of Medicine, Kyoto University
2017-
Advisor, Shizuoka Prefectural University Corporation
2017-
Distinguished Professor, Kyoto University Institute for Advanced Study
2015-
President, Foundation for Biomedical Research and Innovation at Kobe (current Kobe Biomedical Innovation Center (KBIC))
2015-2016
Visiting Professor, Affiliate Graduate School, Graduate School of Medicine, Kyoto University
2012-2017
Chairman, Board of Directors, Shizuoka Prefectural University Corporation
2006-2017
Visiting Professor, Endowed Chair, Graduate School of Medicine, Kyoto University (Department of Immunology and Genomic Medicine)
2006-2012
Executive Member, Council for Science and Technology Policy, Cabinet Office
2005-
Specially-Appointed Professor, Graduate School of Medicine, Kyoto University (Department of Immunology and Genomic Medicine)
2004-2006
Director, Research Center for Science Systems, Japan Society for the Promotion of Science (dual appointment)
2002-2004
Dean, Faculty of Medicine/Graduate School of Medicine, Kyoto University (dual appointment)
1999-2004
Science Adviser, Higher Education Bureau (dual appointment)
1996-2000
Dean, Faculty of Medicine/Graduate School of Medicine, Kyoto University (dual appointment)
1995-2005
Professor, Graduate School of Medicine, Kyoto University (Molecular Biology)
1989-1998
Professor, School of Medicine, Hirosaki University (Department of Molecular Genetics Institute of Neurological Disease) (dual appointment)
1988-1997
Director, Center for Molecular Biology and Genetics, Kyoto University (dual appointment)
1984
Professor, Faculty of Medicine, Kyoto University (Department of Medical Chemistry)
1982-1983
Professor, Faculty of Medicine, Kyoto University (Immunology Research Institute) (dual appointment)
1979-1984
Professor, School of Medicine, Osaka University (Department of Genetics)
1977
Visiting Fellow and Associate, Laboratory of Molecular Genetics National Institute of Child Health and Human Development, NIH Bethesda
1974-1979
Assistant Professor, Faculty of Medicine, The University of Tokyo (Department of Physiological Chemistry and Nutrition)
1973-1974
Visiting Fellow and Associate, Laboratory of Molecular Genetics National Institute of Child Health and Human Development, NIH Bethesda
1971-1973
Fellow, Carnegie Institution of Washington (Department of Embryology)

Degree

M.D., Ph.D.

Awards/Honors

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

Membership

  • Honorary Member, Japanese Society for Immunology (President 1999-2000)
  • The Molecular Biology Society of Japan
  • Honorary Member, the Japanese Biomedical Society
  • 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

●Studies on immunoglobulin genes and antibody class switching

  • 1. Organization of immunoglobulin heavy chain genes and allelic deletion model. Honjo, T. and Kataoka, T. Proc. Natl. Acad. Sci. USA 75 2140-2144 (1978)
  • 2. Cloning and complete nucleotide sequence of mouse imunoglobulin g1 chain gene. Honjo, T., Obata, M., Yamawaki-Kataoka, Y., Kataoka, T., Kawakami, T., Takahashi, N. and Mano, Y. Cell 18 559-568 (1979)
  • 3. Rearrangement of immunoglobulin g1-chain gene and mechanism for heavy-chain class switch. Kataoka, T., Kawakami, T., Takahashi, N. and Honjo, T. Proc. Natl. Acad. Sci. USA 77 919-923 (1980)
  • 4. Deletion of immunoglobulin heavy chain genes from expressed allelic chromosome. Yaoita, Y. and Honjo, T. Nature 286 850-853 (1980)
  • 5. Repetitive sequences in class-switch recombination regions of immunoglobulin heavy chain genes. Kataoka, T., Miyata, T. and Honjo, T. Cell 23 357-368 (1981)
  • 6. Switch region of the immunoglobulin Cg gene is composed of simple tandem repetitive sequences. Nikaido, T., Nakai, S. and Honjo, T. Nature 292 845-848 (1981)
  • 7. Ordering of mouse immunoglobulin heavy chain genes by molecular cloning. Shimizu, A., Takahashi, N., Yamawaki-Kataoka, Y., Nishida, Y., Kataoka, T. and Honjo, T. Nature 289 149-153 (1981)
  • 8. Organization of the constant-region gene family of the mouse immunoglobulin heavy chain. Shimizu, A., Takahashi, N., Yaoita, Y. and Honjo, T. Cell 28 499-506 (1982)
  • 9. Cloning of cDNA encoding the murine IgG1 induction factor by a novel strategy using SP6 promoter. Noma, Y., Sideras, P., Naito, T., Bergstedt-Lindquist, S., Azuma, C., Severinson, E., Tanabe, T., Kinashi, T., Matsuda, F., Yaoita, Y. and Honjo, T. Nature 319 640-646 (1986)
  • 10. Cloning of complementary DNA encoding T-cell replacing factor and identity with B-cell growth factor II. 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. Nature 324 70-73 (1986)
  • 11. Circular DNA is excised by immunoglobulin class switch recombination. Iwasato, T., Shimizu, A., Honjo, T. and Yamagishi, H. Cell 62 143-149 (1990)
  • 12. Signal sequence trap: cloning strategy for secreted proteins and type I membrane proteins. Tashiro, K., Tada, H., Heilker, R., Shirozu, M., Nakano, T. and Honjo, T. Science 261 600-603 (1993)
  • 13. The complete nucleotide sequence of the human immunoglobulin heavy chain variable region locus. Matsuda, F., Ishii, K., Bourvagnet, P., Kuma, K., Hayashida, H., Miyata, T. and Honjo, T. J. Exp. Med. 188 2151-2162 (1998)
  • 14. Target specificity of immunoglobulin class switch recombination is not determined by nucleotide sequences of S regions. Kinoshita, K., Tashiro, J., Tomita, S., Lee, C-G. and Honjo, T. Immunity 9 849-858 (1998)
  • 15. Specific expression of activation-induced cytidine deaminase (AID), a novel member of the RNA editing deaminase family in germinal center B cells. Muramatsu, M., Sankaranand, V. S., Anant, S., Sugai, M., Kinoshita, K., Davidson, N. O. and Honjo, T. J. Biol. Chem. 274 18470-18476 (1999)
  • 16. Class switch recombination and hypermutation require activation- induced cytidine deaminase (AID), a potential RNA editing enzyme. Muramatsu, M., Kinoshita, K., Fagarasan, S., Yamada, S., Shinkai, Y. and Honjo, T. Cell 102 553-563 (2000)
  • 17. Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the hyper-IgM syndrome (HIGM2). 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. Cell 102 565-575 (2000)
  • 18. AID is required to initiate Nbs 1/??H2AX focus formation and mutations at sites of class switching. 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. Nature 414 660-665 (2001)
  • 19. In situ class switching and differentiation to IgA-producing cells in the gut lamina propria. Fagarasan, S., Kinoshita, K., Muramatsu, M., Ikuta, K. and Honjo, T. Nature 413 639-643 (2001)
  • 20. Variable deletion and duplication at recombination junction ends: implication for staggered double-strand cleavage in class switch recombination. Chen, X., Kinoshita, K. and Honjo, T. Proc. Natl. Acad. Sci. USA 98 13860-13865 (2001)
  • 21. The AID enzyme induces class switch recombination in fibroblasts. Okazaki, I., Kinoshita, K., Muramatsu, M., Yoshikawa, K. and Honjo, T. Nature 416 340-345 (2002)
  • 22. The AID enzyme induces hypermutation in an actively transcribed gene in fibroblasts. Yoshikawa, K., Okazaki, I., Eto, T., Kinoshita, K., Muramatsu, M., Nagaoka, H. and Honjo, T. Science 296 2033-2036 (2002)
  • 23. Constitutive expression of AID leads to tumorigenesis. Okazaki, I., Hiai, H., Kakazu, N., Yamada, S., Muramatsu, M., Kinoshita, K. and Honjo, T. J. Exp. Med. 197 1173-1181 (2003)
  • 24. AID mutant analyses indicate requirement for class-switch-specific cofactors. 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. Nature Immunol. 4 843-848 (2003)
  • 25. Uracil DNA glycosylase activity is dispensable for immunoglobulin class switch. Begum, N. A., Kinoshita, K., Kakazu, N., Muramatsu, M., Nagaoka, H., Shinkura, R., Biniszkiewicz, D., Boyer, L. A., Jaenisch, R. and Honjo, T. Science 305 1160-1163 (2004)
  • 26. AID-induced decrease in topoisomerase 1 induces DNA structural alteration and DNA cleavage for class switch recombination.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.Proc Natl Acad Sci U S A. 106:22375-80 (2009)
  • 27. Histone3 lysine4 trimethylation regulated by the facilitates chromatin transcription complex is critical for DNA cleavage in class switch recombination. Stanlie A, Aida M, Muramatsu M, Honjo T, Begum NA.Proc Natl Acad Sci U S A. 107:22190-5 (2010)
  • 28. Mice carrying a knock-in mutation of Aicda resulting in a defect in somatic hypermutation have impaired gut homeostasis and compromised mucosal defense. Wei M, Shinkura R, Doi Y, Maruya M, Fagarasan S, Honjo T. Nat Immunol. 12:264-70 (2011)
  • 29. The AID dilemma: infection, or cancer? Honjo T, Kobayashi M, Begum N, Kotani A, Sabouri S, Nagaoka H. Adv Cancer Res. 113:1-44 (2012)
  • 30. Nonimmunoglobulin target loci of activation-induced cytidine deaminase (AID) share unique features with immunoglobulin genes. Kato L, Begum NA, Burroughs AM, Doi T, Kawai J, Daub CO, Kawaguchi T, Matsuda F, Hayashizaki Y, Honjo T. Proc Natl Acad Sci U S A. 109 :2479-84 (2012)
  • 31. Chromatin reader Brd4 functions in Ig class switching as a repair complex adaptor of nonhomologous end-joining. Stanlie A, Yousif AS, Akiyama H, Honjo T, Begum NA. Mol Cell 55:97-110 (2014)
  • 32. Identification of DNA cleavage- and recombination-specific hnRNP cofactors for activation-induced cytidine deaminase. Hu W, Begum NA, Mondal S, Stanlie A, Honjo T. Proc Natl Acad Sci U S A. 112:5791-6 (2015)
  • 33. Chromatin remodeller SMARCA4 recruits topoisomerase 1 and suppresses transcription-associated genomic instability. Husain,A., Begum, NA., Taniguchi, T., Taniguchi, H., Kobayashi, M. and Honjo, T. Nature Communications 7, Article number:10549. doi:10.1038/ncomms10549

●Studies on immune-inhibitory receptor PD-1

  • 1. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. Ishida, Y., Agata, Y., Shibahara, K. and Honjo, T. EMBO J. 11 3887-3895 (1992)
  • 2. Development of lupus-like autoimmune disease by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Nishimura, H., Nose, M., Hiai, H., Minato, N. and Honjo, T. Immunity 11 141-151 (1999)
  • 3. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. 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. J. Exp. Med. 192 1027-1034 (2000)
  • 4. PD-L2, a novel B7 homologue, is a second ligand for PD-1 and inhibits T cell activation. 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. Nature Immunol. 2 261-268 (2001)
  • 5. Autoimmune dilated cardiomyopathy in PD-1 receptor deficient mice. Nishimura, H., Tanaka, Y., Okazaki, T., Nakatani, K., Hara, M., Matsumori, A., Sasayama, S., Hiai, H., Minato, N. and Honjo, T. Science 291 319-322 (2001)
  • 6. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Iwai, Y., Shida, M., Tanaka, Y., Okazaki, T., Honjo, T. and Minato, N. Proc. Natl. Acad. Sci. USA 99 12293-12297 (2002)
  • 7. Autoantibodies against cardiac troponin I are responsible for the dilated cardiomyopathy in PD-1 deficient mice. Okazaki, T., Tanaka, Y., Nishio, R., Mitsuie, T., Mizoguchi, A., Jian, W., Ishida, M., Matsumori, A., Minato,. N. and Honjo, T. Nature Medicine 9 1477-1483 (2003)
  • 8. Rejuvenating exhausted T cells during chronic viral infection. Okazaki, T. and Honjo, T. Cell. 124(3):459-61 (2006)
  • 9. Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. 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. PNAS. 104(9):3360-5 (2007)
  • 10. TRIM28 prevents autoinflammatory T cell development in vivo. Chikuma, S., Suita, N., Okazaki, IM., Shibayama, S. and Honjo, T. Nat Immunol. 13(6):596-603 (2012)
  • 11. A rheostat for immune responses: the unique properties of PD-1 and their advantages for clinical application. Okazaki, T., Chikuma, S., Iwai, Y., Fagarasan, S. and Honjo, T. Nat Immunol. 14(12):1212-8 Review (2013)

●Studies on cell differentiation by Notch target genes RBP-J

  • 1. A protein binding to the Jk recombination sequence of immunoglobulin genes contains a sequence related to the integrase motif. Matsunami, N., Hamaguchi, Y., Yamamoto, Y., Kuze, K., Kangawa, K., Matsuo, H., Kawaichi M. and Honjo, T. Nature 342 934-937 (1989)
  • 2. The Drosophila homolog of the immunoglobulin recombination signal-binding protein regulates peripheral nervous system development. Furukawa, T., Maruyama, S., Kawaichi, M. and Honjo, T. Cell 69 1191-1197 (1992)
  • 3. 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. Zimber-Strobl, U., Strol, L. J., Meitinger, C., Hinrichs, R.,Sakai, T., Furukawa, T., Honjo, T. and Bornkamm. G. W. EMBO. J. 13 4973-4982 (1994)
  • 4. Physical interaction between a novel domain of the receptor notch and the transcription factor RBP-Jk/Su(H). Tamura, K., Taniguchi, Y., Minoguchi, S., Sakai, T., Tin Tun, Furukawa, T. and Honjo, T. Curr. Biol. 5 1416-1423 (1995)
  • 5. Disruption of the mouse RBP-Jk gene results in early embryonic death. Oka, C., Nakano, T., Wakeham, A., Mori, C., Sakai, T., Okazaki, S., Kawaichi, M., Shiota, K., Mak, T. and Honjo, T. Development 121 3291-3301 (1995)
  • 6. Involvement of RBP-J in biological functions of mouse Notch 1 and its derivatives. Kato, H., Taniguchi, Y., Kurooka, H., Minoguchi, S., Sakai, T., Nomura-Okazaki, S., Tamura, K. and Honjo, T. Development 124 4133-4141 (1997)
  • 7. Notch-signalling controls pancreatic cell differentiation. Apelqviist, A., Li, H., Sommer, L., Beatus, P., Anderson, D. J., Honjo, T., de Hrabe, M. H., Lendahl, U. and Edlund, H. Nature 400 877-881 (1999)
  • 8. Notch / RBP-J signaling is involved in cell fate determination of marginal zone B cells. Tanigaki, K., Han, H., Yamamoto, N., Tashiro, K., Ikegawa, M., Kuroda, K. and Honjo, T. Nature Immunol. 3 443-450 (2002)
  • 9. Regulation of marginal zone B cell development by MINT, a suppressor of Notch/RBP-J signaling pathway. Kuroda, K., Han, H., Tani, S., Tanigaki, K., Tin Tun, Furukawa, T., Taniguchi, Y., Kurooka, H., Hamada, Y., Toyokuni, S. and Honjo, T. Immunity 18 1-20 (2003)
  • 10. Regulation of ab gd T cell lineage commitment and peripheral T cell response by Notch/RBP-J signaling. Tanigaki, K., Tsuji, M., Yamamoto, N., Han, H., Tsukada, J., Inoue, H., Kubo, M and Honjo, T. Immunity 20 611-622 (2004)
  • 11. Instruction of distinct CD4 T helper cell fates by different Notch ligands on antigen-presenting cells. Amsen, D., Blander, J. M., Lee, G. R., Tanigaki, K., Honjo, T. and Flavell, R. A. Cell 117 515-526 (2004)

●Studies on isolation of IL-2 receptor alpha chain

  • 1. Molecular cloning of cDNA encoding human interleukin-2 receptor. Nikaido, T., Shimizu, A., Ishida, N., Sabe, H., Teshigawara, K., Maeda, M., Uchiyama, T., Yodoi, J. and Honjo, T. Nature 311 631-635 (1984)
  • 2. Expression of functional human interleukin 2 receptor in mouse T cells by cDNA transfection. Kondo, S., Shimizu, A., Maeda, M., Tagaya, Y., Yodoi, J. and Honjo, T. Nature 320 75-77 (1986)
  • 3. Expression and functional characterization of artificial mutants of interleukin-2 receptor. Kondo, S., Kinoshita, M., Shimizu, A., Saito, Y., Konishi, M., Sabe, H. and Honjo, T. Nature 327 64-67 (1987)
  • 4. Expression of functional interleukin-2 receptors in human light chain/Tac transgenic mice. Nishi, M., Ishida, Y. and Honjo, T. Nature 331 267-269 (1988)
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