Hatano, Hiroaki

写真a

Affiliation

School of Medicine, Department of Microbiology and Immunology ( Shinanomachi )

Position

Instructor

External Links
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Academic Background 【 Display / hide 】

  • 2006.04
    -
    2008.03

    The University of Tokyo, 教養学部, 理科三類

    University, Completed

  • 2008.04
    -
    2012.03

    The University of Tokyo, 医学部, 医学科

    University, Graduated

  • 2016.04
    -
    2020.03

    The University of Tokyo, 医学部, 医学系研究科内科学専攻

    Graduate School, Graduated, Doctoral course

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Academic Degrees 【 Display / hide 】

  • 博士（医学）, The University of Tokyo, Coursework, 2020.03

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Licenses and Qualifications 【 Display / hide 】

  • 医師免許, 2012.03

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Papers 【 Display / hide 】

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

    Michihiro Kono, Hiroaki Hatano, Kenichiro Asahara, Masahiro Nakano, Reza Bagherzadeh, Tsugumi Kawashima, Takahiro Arakawa, Miho Sato, Hajime Inokuchi, Takahiro Nishino, Takahiro Itamiya, Haruka Takahashi, Bunki Natsumoto, Akari Suzuki, Kazuhiko Yamamoto, Kazuyoshi Ishigaki

    Nature communications (Cold Spring Harbor Laboratory)   2026.07

    　View Summary

    Abstract

    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 LEF1 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.

  • T cell plasticity in systemic lupus erythematosus revealed by large-scale T cell receptor repertoire and transcriptome studies

    Yasuo Nagafuchi, Masahiro Nakano, Kaitlyn A. Lagattuta, Mineto Ota, Hiroaki Hatano, Haruka Takahashi, Takahiro Itamiya, Hajime Inokuchi, Soumya Raychaudhuri, Tomohisa Okamura, Keishi Fujio, Kazuyoshi Ishigaki

    Arthritis & rheumatology (Hoboken, N.J.) (Cold Spring Harbor Laboratory)   2025.01

    ISSN  2326-5191

    　View Summary

    Abstract

    CD4+ T cell plasticity plays a pivotal role in immune homeostasis. However, evidence of T cell plasticity and its pathological role in human systemic lupus erythematosus (SLE) is missing due to the lack of a reporter system. Here we utilized T cell receptor (TCR) repertoire data as a molecular signatures alongside transcriptomic dataset. Using a large-scale ImmuNexUT database of autoimmune disease patients including 117 SLE cases, we quantified T cell plasticity across 13 fine-grained T cell-types. We analyzed 6,392 samples in total and identified two orthogonal signatures of repertoire and transcriptome, the cell-type and disease signatures, allowing us to investigate CD4+ T cell plasticity comprehensively. Among all possible patterns, the plasticity level was the highest in effector regulatory T cells (eTreg) to Th1 plasticity, which was replicated in an independent cohort. Moreover, eTreg-to-Th1 plasticity positively correlated with SLE disease activity. Our study provides novel evidence that Treg plasticity is involved in SLE pathology.

  • Single-cell RNA sequencing of peripheral blood links cell-type-specific regulation of splicing to autoimmune and inflammatory diseases.

    Chi Tian, Yuntian Zhang, Yihan Tong, Kian Hong Kock, Donald Yuhui Sim, Fei Liu, Jiaqi Dong, Zhixuan Jing, Wenjing Wang, Junbin Gao, Le Min Tan, Kyung Yeon Han, Yoshihiko Tomofuji, Masahiro Nakano, Eliora Violain Buyamin, Radhika Sonthalia, Yoshinari Ando, Hiroaki Hatano, Kyuto Sonehara, Xin Jin, Marie Loh, John Chambers, Chung-Chau Hon, Murim Choi, Jong-Eun Park, Kazuyoshi Ishigaki, Tomohisa Okamura, Keishi Fujio, Yukinori Okada, Woong-Yang Park, Jay W Shin, Xavier Roca, Shyam Prabhakar, Boxiang Liu

    Nature genetics 56 ( 12 ) 2739 - 2752 2024.12

    ISSN  1061-4036

    　View Summary

    Alternative splicing contributes to complex traits, but whether this differs in trait-relevant cell types across diverse genetic ancestries is unclear. Here we describe cell-type-specific, sex-biased and ancestry-biased alternative splicing in ~1 M peripheral blood mononuclear cells from 474 healthy donors from the Asian Immune Diversity Atlas. We identify widespread sex-biased and ancestry-biased differential splicing, most of which is cell-type-specific. We identify 11,577 independent cis-splicing quantitative trait loci (sQTLs), 607 trans-sGenes and 107 dynamic sQTLs. Colocalization between cis-eQTLs and trans-sQTLs revealed a cell-type-specific regulatory relationship between HNRNPLL and PTPRC. We observed an enrichment of cis-sQTL effects in autoimmune and inflammatory disease heritability. Specifically, we functionally validated an Asian-specific sQTL disrupting the 5' splice site of TCHP exon 4 that putatively modulates the risk of Graves' disease in East Asian populations. Our work highlights the impact of ancestral diversity on splicing and provides a roadmap to dissect its role in complex diseases at single-cell resolution.

  • An atlas of transcribed enhancers across helper T cell diversity for decoding human diseases

    Akiko Oguchi, Akari Suzuki, Shuichiro Komatsu, Hiroyuki Yoshitomi, Shruti Bhagat, Raku Son, Raoul Jean Pierre Bonnal, Shohei Kojima, Masaru Koido, Kazuhiro Takeuchi, Keiko Myouzen, Gyo Inoue, Tomoya Hirai, Hiromi Sano, Yujiro Takegami, Ai Kanemaru, Itaru Yamaguchi, Yuki Ishikawa, Nao Tanaka, Shigeki Hirabayashi, Riyo Konishi, Sho Sekito, Takahiro Inoue, Juha Kere, Shunichi Takeda, Akifumi Takaori-Kondo, Itaru Endo, Shinpei Kawaoka, Hideya Kawaji, Kazuyoshi Ishigaki, Hideki Ueno, Yoshihide Hayashizaki, Massimiliano Pagani, Piero Carninci, Motoko Yanagita, Nicholas Parrish, Chikashi Terao, Kazuhiko Yamamoto, Yasuhiro Murakawa, Matteo Guerrini, Hiroaki Hatano, Michihiro Kono, Masahiro Nakano, Kohei Tomizuka, Soichiro Yoshino

    Science (American Association for the Advancement of Science (AAAS))  385 ( 6704 )  2024.07

    ISSN  00368075

    　View Summary

    <jats:p>
    Transcribed enhancer maps can reveal nuclear interactions underpinning each cell type and connect specific cell types to diseases. Using a 5′ single-cell RNA sequencing approach, we defined transcription start sites of enhancer RNAs and other classes of coding and noncoding RNAs in human CD4
    <jats:sup>+</jats:sup>
    T cells, revealing cellular heterogeneity and differentiation trajectories. Integration of these datasets with single-cell chromatin profiles showed that active enhancers with bidirectional RNA transcription are highly cell type–specific and that disease heritability is strongly enriched in these enhancers. The resulting cell type–resolved multimodal atlas of bidirectionally transcribed enhancers, which we linked with promoters using fine-scale chromatin contact maps, enabled us to systematically interpret genetic variants associated with a range of immune-mediated diseases.
    </jats:p>

  • Epigenetic targets of Janus kinase inhibitors are linked to genetic risks of rheumatoid arthritis.

    Haruka Tsuchiya, Mineto Ota, Haruka Takahashi, Hiroaki Hatano, Megumi Ogawa, Sotaro Nakajima, Risa Yoshihara, Tomohisa Okamura, Shuji Sumitomo, Keishi Fujio

    Inflammation and regeneration 44 ( 1 ) 29 - 29 2024.06

    ISSN  1880-9693

    　View Summary

    BACKGROUND: Current strategies that target cytokines (e.g., tumor necrosis factor (TNF)-α), or signaling molecules (e.g., Janus kinase (JAK)) have advanced the management for allergies and autoimmune diseases. Nevertheless, the molecular mechanism that underpins its clinical efficacy have largely remained elusive, especially in the local tissue environment. Here, we aimed to identify the genetic, epigenetic, and immunological targets of JAK inhibitors (JAKis), focusing on their effects on synovial fibroblasts (SFs), the major local effectors associated with destructive joint inflammation in rheumatoid arthritis (RA). METHODS: SFs were activated by cytokines related to inflammation in RA, and were treated with three types of JAKis or a TNF-α inhibitor (TNFi). Dynamic changes in transcriptome and chromatin accessibility were profiled across samples to identify drug targets. Furthermore, the putative targets were validated using luciferase assays and clustered regularly interspaced short palindromic repeat (CRISPR)-based genome editing. RESULTS: We found that both JAKis and the TNFi targeted the inflammatory module including IL6. Conversely, specific gene signatures that were preferentially inhibited by either of the drug classes were identified. Strikingly, RA risk enhancers for CD40 and TRAF1 were distinctively regulated by JAKis and the TNFi. We performed luciferase assays and CRISPR-based genome editing, and successfully fine-mapped the single causal variants in these loci, rs6074022-CD40 and rs7021049-TRAF1. CONCLUSIONS: JAKis and the TNFi had a direct impact on different RA risk enhancers, and we identified nucleotide-resolution targets for both drugs. Distinctive targets of clinically effective drugs could be useful for tailoring the application of these drugs and future design of more efficient treatment strategies.

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Reviews, Commentaries, etc. 【 Display / hide 】

  • リウマチ性疾患の基礎研究2　eQTL効果を単一細胞レベルで可視化する新規レポーターT細胞システムの開発

    河野 通大, 波多野 裕明, 夏本 文輝, 石垣 和慶

    日本リウマチ学会総会・学術集会プログラム・抄録集 ((一社)日本リウマチ学会)  70回   644 - 644 2026.03

  • GRN-CCAを用いた関節リウマチ(RA)に関わる転写因子(TF)とその下流の遺伝子群の解析による病態解明

    春田 煌天, 高橋 悠, 波多野 裕明, 稲毛 純, 石垣 和慶

    日本リウマチ学会総会・学術集会プログラム・抄録集 ((一社)日本リウマチ学会)  70回   901 - 901 2026.03

  • 【オミクスデータを探す!使いこなす!公共データベース厳選53　情報の海で手に入る宝物で、あなたの研究が発展する!】(第2章)オミクス研究のための公共データベース　ゲノムデータ　GWAS Catalog　最大規模のGWASレジストリを使いこなす

    高橋 悠, 波多野 裕明, 石垣 和慶

    実験医学 ((株)羊土社)  43 ( 20 ) 3200 - 3203 2025.12

    ISSN  0288-5514

  • ゲノム編集技術を用いた遺伝子多型機能解明のピットフォールと対策

    河野 通大, 波多野 裕明, 浅原 健一郎, 高橋 悠, バゲルザデレザ , 川島 麗, 荒川 貴博, 中野 正博, 石垣 和慶

    日本臨床免疫学会総会プログラム・抄録集 ((一社)日本臨床免疫学会)  53回   117 - 117 2025.08

  • 疾患病態に寄与するtranscription factor-gene regulatory networkの解明

    高橋 悠, 波多野 裕明, 中野 正博, 土田 優美, 住友 秀次, 鈴木 亜香里, 高地 雄太, 藤尾 圭志, 山本 一彦, 石垣 和慶

    日本臨床免疫学会総会プログラム・抄録集 ((一社)日本臨床免疫学会)  53回   133 - 133 2025.08

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • Identification of Core Regulators of Splicing Dysregulation in Systemic Lupus Erythematosus and Development of RNA-Targeted Therapeutics

    2026.04
    -
    2029.03

    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists, No Setting

    　View Summary

    自己免疫疾患の発症に関わる遺伝的リスク変異の多くは、タンパク質を直接変化させるのではなく、遺伝子の読み取り方の調節に影響すると考えられている。本研究では、免疫細胞においてリスク変異がmRNAのスプライシング（遺伝子からタンパク質を作る過程での情報の選択的な組み合わせ）に与える影響を網羅的に解析し、疾患との関連を明らかにする。さらに、実験的な検証を通じて、スプライシングの異常が免疫機能にどのような影響を与えるかを解明し、新たな治療標的の発見を目指す。

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Courses Taught 【 Display / hide 】

  • IMMUNOLOGY

    2026

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