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RIKEN Center for Integrative Medical Sciences Laboratory for Human Immunogenetics

Team Leader: Kazuyoshi Ishigaki (M.D., Ph.D.)

Research Summary

Kazuyoshi Ishigaki (M.D., Ph.D.)

Our immune function is regulated by individual differences in the genome sequence (polymorphisms). Previous studies have identified that specific polymorphisms have causal roles in the onset of immune diseases, and drug discovery by genetics research (genetic drug discovery) is drawing attention. However, since the immune system is highly complex, the immunological functions of the risk polymorphisms have not been elucidated, and there are few successful cases of genetic drug discovery. Our laboratory aims to identify new drug targets through functional elucidation of the risk polymorphisms by utilizing the latest experimental techniques such as genome editing and single-cell multi-omics analysis.

Main Research Fields

  • Medicine, Dentistry & Pharmacy

Related Research Fields

  • Informatics
  • Interdisciplinary Science & Engineering
  • Biological Sciences
  • Biology

Keywords

  • Functional genetics
  • Genome-wide association study
  • Genome editing
  • Single-cell analysis
  • T cell receptor

Selected Publications

Papers with an asterisk(*) are based on research conducted outside of RIKEN.

  • 1. *Ishigaki K, Lagattuta KA, Luo Y, James EA, Buckner JH, Raychaudhuri S.
    "HLA autoimmune risk alleles restrict the hypervariable region of T cell receptors."
    Nature Genetics. 54(4):393-402 (2022)
  • 2. *Lagattuta KA, Kang JB, Nathan A, Pauken KE, Jonsson AH, Rao DA, Sharpe AH, Ishigaki K (co-corresponding author), Raychaudhuri S.
    "Repertoire analyses reveal T cell antigen receptor sequence features that influence T cell fate."
    Nature Immunology. 23(3):446-457 (2022)
  • 3. *Nathan A, Asgari S, Ishigaki K, Valencia C, Amariuta T, Luo Y, Beynor JI, Baglaenko Y, Suliman S, Price AL, Lecca L, Murray MB, Moody DB, Raychaudhuri S.
    "Single-cell eQTL models reveal dynamic T cell state dependence of disease loci."
    Nature. 606(7912):120-128 (2022)
  • 4. *Ota M, Nagafuchi Y, Hatano H, Ishigaki K, Terao C, Takeshima Y, Yanaoka H, Kobayashi S, Okubo M, Shirai H, Sugimori Y, Maeda J, Nakano M, Yamada S, Yoshida R, Tsuchiya H, Tsuchida Y, Akizuki S, Yoshifuji H, Ohmura K, Mimori T, Yoshida K, Kurosaka D, Okada M, Setoguchi K, Kaneko H, Ban N, Yabuki N, Matsuki K, Mutoh H, Oyama S, Okazaki M, Tsunoda H, Iwasaki Y, Sumitomo S, Shoda H, Kochi Y, Okada Y, Yamamoto K, Okamura T, Fujio K.
    "Dynamic landscape of immune cell-specific gene regulation in immune-mediated diseases."
    Cell. 27;184(11):3006-3021.e17 (2021)
  • 5. Ishigaki K, Akiyama M, Kanai M, Takahashi A, Kawakami E, Sugishita H, Sakaue S, Matoba N, Low SK, Okada Y, Terao C, Amariuta T, Gazal S, Kochi Y, Horikoshi M, Suzuki K, Ito K, Koyama S, Ozaki K, Niida S, Sakata Y, Sakata Y, Kohno T, Shiraishi K, Momozawa Y, Hirata M, Matsuda K, Ikeda M, Iwata N, Ikegawa S, Kou I, Tanaka T, Nakagawa H, Suzuki A, Hirota T, Tamari M, Chayama K, Miki D, Mori M, Nagayama S, Daigo Y, Miki Y, Katagiri T, Ogawa O, Obara W, Ito H, Yoshida T, Imoto I, Takahashi T, Tanikawa C, Suzuki T, Sinozaki N, Minami S, Yamaguchi H, Asai S, Takahashi Y, Yamaji K, Takahashi K, Fujioka T, Takata R, Yanai H, Masumoto A, Koretsune Y, Kutsumi H, Higashiyama M, Murayama S, Minegishi N, Suzuki K, Tanno K, Shimizu A, Yamaji T, Iwasaki M, Sawada N, Uemura H, Tanaka K, Naito M, Sasaki M, Wakai K, Tsugane S, Yamamoto M, Yamamoto K, Murakami Y, Nakamura Y, Raychaudhuri S, Inazawa J, Yamauchi T, Kadowaki T, Kubo M, Kamatani Y.
    "Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases."
    Nature Genetics. 52(7): 669-679 (2020)
  • 6. Terao C, Suzuki A, Momozawa Y, Akiyama M, Ishigaki K, Yamamoto K, Matsuda K, Murakami Y, McCarroll SA, Kubo M, Loh PR, Kamatani Y.
    "Chromosomal alterations among age-related haematopoietic clones in Japan."
    Nature. 584(7819): 130-135 (2020)
  • 7. *Amariuta T, Ishigaki K (co-first author), Sugishita H, Ohta T, Koido M, Dey KK, Matsuda K, Murakami Y, Price AL, Kawakami E, Terao C, Raychaudhuri S.
    "Improving the trans-ancestry portability of polygenic risk scores by prioritizing variants in predicted cell-type-specific regulatory elements."
    Nature Genetics. 52(12): 1346-1354 (2020)
  • 8. Akiyama M, Ishigaki K, Sakaue S, Momozawa Y, Horikoshi M, Hirata M, Matsuda K, Ikegawa S, Takahashi A, Kanai M, Suzuki S, Matsui D, Naito M, Yamaji T, Iwasaki M, Sawada N, Tanno K, Sasaki M, Hozawa A, Minegishi N, Wakai K, Tsugane S, Shimizu A, Yamamoto M, Okada Y, Murakami Y, Kubo M, Kamatani Y.
    "Characterizing rare and low-frequency height-associated variants in the Japanese population."
    Nature Communications. 27;10(1): 4393 (2019)
  • 9. Ishigaki K, Kochi Y, Suzuki A, Tsuchida Y, Tsuchiya H, Sumitomo S, Yamaguchi K, Nagafuchi Y, Nakachi S, Kato R, Sakurai K, Shoda H, Ikari K, Taniguchi A, Yamanaka H, Miya F, Tsunoda T, Okada Y, Momozawa Y, Kamatani Y, Yamada R, Kubo M, Fujio K, Yamamoto K.
    "Polygenic burdens on cell-specific pathways underlie the risk of rheumatoid arthritis."
    Nature Genetics. 49(7):1120-1125 (2017)
  • 10. *Ishigaki K, Shoda H, Kochi Y, Yasui T, Kadono Y, Tanaka S, Fujio K, Yamamoto K.
    "Quantitative and qualitative characterization of expanded CD4+ T cell clones in rheumatoid arthritis patients."
    Scientific Reports. 6;5:12937 (2015)

Related Links

Lab Members

Principal investigator

Kazuyoshi Ishigaki
Team Leader

Core members

Michihiro Kono
Postdoctoral Researcher
Hiroaki Hatano
Postdoctoral Researcher
Takahiro Arakawa
Technical Staff I

Contact Information

1-7-22 Suehiro-cho, Tsurumi-ku,
Yokohama City, Kanagawa,
230-0045, Japan
Tel: +81-(0)45-503-7072
Email: kazuyoshi.ishigaki [at] riken.jp

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