KEIO RESEARCHERS INFORMATION SYSTEM

Profile 【 Display / hide 】

Profile 【 Display / hide 】

• Individual differences—or polymorphisms—in our genomic sequences are fundamental determinants of immune function. While recent research has linked specific polymorphisms to the development of immune-mediated diseases, the immense complexity of the immune system often masks the underlying biological mechanisms. Consequently, translating these genetic insights into successful 'genome-based drug discovery' remains a significant challenge.
  Our laboratory is dedicated to bridging this gap. By integrating cutting-edge technologies—including CRISPR genome editing, single-cell analysis, and multi-omics approaches—we aim to elucidate the functional roles of disease-risk polymorphisms and identify novel therapeutic targets for immune disorders.

Papers 【 Display / hide 】

Papers 【 Display / hide 】

• Host Genetic Architecture between Epstein-Barr Virus Activity and Multiple Sclerosis Reveals Shared Pathways.

  Yasumizu Y, Kim N, Rivier CA, Moon J, Kojima S, Chen HL, Buitrago-Pocasangre N, Quinn E, Vaughn S, Morgan A, Huo S, Silberfeld A, Sumida TS, Ishigaki K, Longbrake EE, Falcone GJ, Hafler DA

  medRxiv : the preprint server for health sciences  2025.12

  • Access to Document (DOI)

• The dynamic role of HLA proteins on compositional alterations of T-cell repertoires in inflammatory bowel disease

   2025.10

  • Access to Document (DOI)

• Nonrandomized Allocation of Steroid Therapy in Patients With Fukuyama Congenital Muscular Dystrophy: Study Protocol for a Phase II Clinical Trial.

  Murakami T, Sato T, Ishizuka T, Nakamura H, Tachimori H, Harada H, Oi H, Hatano K, Oba MS, Ishiguro K, Shichiji M, Kihara Y, Takeshima Y, Taniguchi-Ikeda M, Hattori A, Shimizu-Motohashi Y, Awano H, Bo R, Nagata S, Ishigaki K

  Neuropsychopharmacology reports 45 ( 3 ) e70043 2025.09

  • Access to Document (DOI)

• Tracking clonal dynamics of CD8 T cells and immune dysregulation in progression of systemic lupus erythematosus with nephritis

  Paek S.J., Lee H.S., Lee Y.J., Bang S.Y., Kim D., Kang B.K., Park D.J., Joo Y.B., Kim M., Kim H., Park S.Y., Park W.Y., Abe T., Itamiya T., Nagafuchi Y., Ishigaki K., Fujio K., Kim K.T., Bae S.C.

  Experimental and Molecular Medicine 57 ( 8 ) 1700 - 1710 2025.08

  ISSN  12263613

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  The fluctuating nature of disease activity in systemic lupus erythematosus (SLE), alternating between flares and remissions, poses substantial challenges for its effective management. The use of current biomarkers for monitoring SLE is limited in clinical settings owing to insufficient comprehension of the complex immune involvement underlying the disease course. Here, therefore, we profiled peripheral blood mononuclear cells at both stable and exacerbation states (total of n = 19) from six patients with SLE and 32 healthy donors using integrated single-cell RNA and T cell receptor (TCR) sequencing. To validate our findings, we analyzed two independent external datasets: bulk RNA sequencing and TCR data from 79 controls and 62 patients with SLE and single-cell RNA sequencing data from 99 healthy controls and 162 patients with SLE. Our analysis revealed cell type-specific activation of interferon-related genes in SLE grouped into four clusters, with elevated activity in disease-associated immune cells. Among these, atypical B cells associated with autoantibody production exhibited distinct differentiation patterns compared with conventional memory B cells, driven by heightened interferon signaling in SLE. Notably, clonal expansion of effector CD8 T cells emerged as a key driver of disease exacerbation, as indicated by reduced TCR diversity. Specific CD8 T cell clonotypes expanded during flare states, transitioning to effector phenotypes that exhibited heightened cytotoxicity and amplified interferon signaling, strongly correlating with tissue damage and flare severity. Our findings establish a critical link between interferon-driven mechanisms and cytotoxic T cell dysfunction in SLE flares, offering potential targets for therapeutic intervention and predictive biomarkers.

  • Access to Document (DOI)

• Accurate, sensitive, and efficient chromatin accessibility quantification at target loci using UNIChro-seq

   2025.07

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  <jats:title>Abstract</jats:title>
  <jats:p>Recent progress in statistical and experimental fine mapping of disease risk variants prompts us to focus on specific target loci for functional investigation. However, current genetics is hindered by a limited toolbox for target-loci analysis. To address this, we developed UNIChro-seq, a method that digitally counts accessible chromatin molecules at target loci. UNIChro-seq allows for accurate, sensitive, and efficient quantification of allelic effects compared to conventional methods. Using UNIChro-seq, we investigated the effects of 57 autoimmunity risk alleles on chromatin accessibility and estimated the causal effects of 20 artificial variants generated through genome editing. As a caveat, non-negligible fraction of the edited allele exhibited a falsely positive effect on chromatin accessibility, which can be effectively distinguished from the true causal effect through bi-directional genome editing. Finally, functional dissection of a fine-mapped risk variant at the <jats:italic>LEF1</jats:italic> locus illuminated its impact on T cell pathology in rheumatoid arthritis. Together, these findings underscore the utility of combining UNIChro-seq with genome editing technology to enable precise and scalable functional analysis of disease-associated loci.</jats:p>

  • Access to Document (DOI)

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Reviews, Commentaries, etc. 【 Display / hide 】

Reviews, Commentaries, etc. 【 Display / hide 】

• Unveiling the dynamics of B lymphocytes in systemic lupus erythematosus patients treated with belimumab through longitudinal single-cell RNA sequencing (Jul, keae364, 2024)

  RHEUMATOLOGY  2025

  • Access to Document (DOI)

• Big Data Science on T Cell Receptor-mediated Immune Regulation

  Ishigaki K

  JMA JOURNAL 8 ( 2 ) 338 - 344 2025

  ISSN  2433-328X

  • Access to Document (DOI)

• Correction to: Interferon subverts an AHR–JUN axis to promote CXCL13+ T cells in lupus (Nature, (2024), 631, 8022, (857-866), 10.1038/s41586-024-07627-2)

  Law C., Wacleche V.S., Cao Y., Pillai A., Sowerby J., Hancock B., Horisberger A., Bracero S., Skidanova V., Li Z., Adejoorin I., Dillon E., Benque I.J., Nunez D.P., Simmons D.P., Keegan J., Chen L., Baker T., Brohawn P.Z., Al-Mossawi H., Hao L.Y., Jones B., Rao N., Qu Y., Alves S.E., Wyse A., Cordle A., Zhu Z., Zhang F., Xiao Q., Weisman M., Weisenfeld D., Weinand K., Wei K., Watts G.F.M., Utz P.J., Tabechian D., Smith M., Slowikowski K., Singaraju A., Scheel-Toellner D., Seifert J.A., Sakaue S., Sahbudin I., Rumker L., Robinson W.H., Rivellese F., Ritchlin C., Reshef Y., Raza K., Raychaudhuri S., Rangel-Moreno J., Pitzalis C., Perlman H., Orange D.E., Nerviani A., Nayar S., Moreland L., Millard N., Meednu N., Mears J.R., McGeachy M.J., McDavid A., Maybury M., Marks K.E., Mantel I., Mandelin A.M., Liao K., Li Y., Lewis M.J., Lederer J.A., Lakhanpal A., Korsunsky I., Keras G., Kang J.B., Jonsson A.H., James J.A., Ishigaki K., Ivashkiv L.B., Hughes L.B., Horowitz D., Holers V.M., Gutierrez-Arcelus M., Guthridge J.M., Gregersen P.K., Gravallese E.M., Goodman S.M., Geraldino-Pardilla L., Forbess L., Firestein G.S., Carr H., Filer A., Dunn P., Donlin L.T., DiCarlo E., Deane K.D., Curtis M., Chicoine A., Ceponis A., Campbell D.

  Nature 632 ( 8025 )  2024.08

  ISSN  00280836

  　View Summary

  In the version of the article initially published, in Fig. 2j, the x-axis labels “AHRinh” and “TCDD” (now middle and right) were switched and have now been corrected in the HTML and PDF versions of the article.

  • Access to Document (DOI)

• Erratum: Identification of a regulatory pathway governing TRAF1 via an arthritis-associated non-coding variant (Cell Genomics (2023) 3(11), (S2666979X2300246X), (10.1016/j.xgen.2023.100420))

  Wang Q., Martínez-Bonet M., Kim T., Sparks J.A., Ishigaki K., Chen X., Sudman M., Aguiar V., Sim S., Hernandez M.C., Chiu D.J., Wactor A., Wauford B., Marion M.C., Gutierrez-Arcelus M., Bowes J., Eyre S., Nordal E., Prahalad S., Rygg M., Videm V., Raychaudhuri S., Weirauch M.T., Langefeld C.D., Thompson S.D., Nigrovic P.A.

  Cell Genomics 4 ( 2 )  2024.02

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  (Cell Genomics 3, 100420; November 8, 2023) Figures 4D, 4E, and 4F were inadvertently omitted from the graphic in the initial publication. The figure has now been corrected in the online article. The authors apologize for the error. [Formula presented] [Formula presented]

  • Access to Document (DOI)

• Identification of telomere maintenance gene variations related to lung adenocarcinoma risk by genome-wide association and whole genome sequencing analyses

  Shiraishi K., Takahashi A., Momozawa Y., Daigo Y., Kaneko S., Kawaguchi T., Kunitoh H., Matsumoto S., Horinouchi H., Goto A., Honda T., Shimizu K., Torasawa M., Takayanagi D., Saito M., Saito A., Ohe Y., Watanabe S.i., Goto K., Tsuboi M., Tsuchihara K., Takata S., Aoi T., Takano A., Kobayashi M., Miyagi Y., Tanaka K., Suzuki H., Maeda D., Yamaura T., Matsuda M., Shimada Y., Mizuno T., Sakamoto H., Yoshida T., Goto Y., Yoshida T., Yamaji T., Sonobe M., Toyooka S., Yoneda K., Masago K., Tanaka F., Hara M., Fuse N., Nishizuka S.S., Motoi N., Sawada N., Nishida Y., Kumada K., Takeuchi K., Tanno K., Yatabe Y., Sunami K., Hishida T., Miyazaki Y., Ito H., Amemiya M., Totsuka H., Nakayama H., Yokose T., Ishigaki K., Nagashima T., Ohtaki Y., Imai K., Takasawa K., Minamiya Y., Kobayashi K., Okubo K., Wakai K., Shimizu A., Yamamoto M., Iwasaki M., Matsuda K., Inazawa J., Shiraishi Y., Nishikawa H., Murakami Y., Kubo M., Matsuda F., Kamatani Y., Hamamoto R., Matsuo K., Kohno T.

  Cancer Communications 44 ( 2 ) 287 - 293 2024.02

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Courses Taught 【 Display / hide 】

Courses Taught 【 Display / hide 】

• ADVANCED MICROBIOLOGY AND IMMUNOLOGY

  2025

• CASE STUDY

  2025

• IMMUNOLOGY

  2025

• INTEGRATION OF BASIC SCIENCE AND CLINICAL MEDICINE

  2025

• MICROBIOLOGY AND IMMUNOLOGY

  2025

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