Takatori Mitsuyoshi

写真a

Title

Assistant Professor

Researcher Number(JSPS Kakenhi)

80974667

Laboratory Address

Room 06-1620, Research Building, 1076 Kiyuna, Ginowan, Okinawa, Japan

Mail Address

E-mail address

Homepage URL

https://ryukyu-physiology.info/

Current Affiliation Organization 【 display / non-display

  • Duty   University of the Ryukyus   Graduate School of Medicine   Assistant Professor  

University 【 display / non-display

  •  
    -
    2017.03

    University of the Ryukyus   Faculty of Medicine   Graduated

  • 2019.04
    -
    2022.03

    University of the Ryukyus   Graduate School of Medicine   Department of Pathology and Cell Biology   Graduated

External Career 【 display / non-display

  • 2022.06
    -
    2023.03

     

  • 2022.06
    -
    2024.03

    Kumamoto University  

  • 2024.04
     
     

    University of the Ryukyus  

Research Interests 【 display / non-display

  • Bioinformatics

  • Amyotrophic lateral sclerosis

  • Hereditary motor and sensory neuropathy with proximal dominant involvement

  • Amyotrophic lateral sclerosis

  • Hereditary motor and sensory neuropathy with proximal dominant involvement

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Research Areas 【 display / non-display

  • Life Science / Hematology and medical oncology

  • Life Science / Psychiatry

  • Life Science / Pathophysiologic neuroscience

  • Life Science / Human pathology

  • Life Science / Virology

Acquisition of a qualification 【 display / non-display

  • Medical Technologist

Published Papers 【 display / non-display

  • Intragenic viral silencer element regulates HTLV-1 latency via RUNX complex recruitment

    Sugata, K; Rahman, A; Niimura, K; Monde, K; Ueno, T; Rajib, SA; Takatori, M; Sakhor, W; Hossain, MB; Sithi, SN; Jahan, MI; Matsuda, K; Ueda, M; Yamano, Y; Ikeda, T; Ueno, T; Tsuchiya, K; Tanaka, Y; Tokunaga, M; Maeda, K; Utsunomiya, A; Okuma, K; Ono, M; Satou, Y

    NATURE MICROBIOLOGY ( Nature Microbiology )  10 ( 6 ) 1447 - 1462   2025.06 [ Peer Review Accepted ]

    Type of publication: Research paper (scientific journal)

     View Summary

    Retroviruses integrate their genetic material into the host genome, enabling persistent infection. Human T cell leukaemia virus type 1 (HTLV-1) and human immunodeficiency virus type 1 (HIV-1) share similarities in genome structure and target cells, yet their infection dynamics differ drastically. While HIV-1 leads to high viral replication and immune system collapse, HTLV-1 establishes latency, promoting the survival of infected cells and, in some cases, leading to leukaemia. The mechanisms underlying this latency preference remain unclear. Here we analyse blood samples from people with HTLV-1 and identify an open chromatin region within the HTLV-1 provirus that functions as a transcriptional silencer and regulates transcriptional burst. The host transcription factor RUNX1 binds to this open chromatin region, repressing viral expression. Mutation of this silencer enhances HTLV-1 replication and immunogenicity, while its insertion into HIV-1 suppresses viral production. These findings reveal a strategy by which HTLV-1 ensures long-term persistence, offering potential insights into retroviral evolution and therapeutic targets.

  • Robust HPV-16 Detection Workflow for Formalin-Fixed Cancer Tissue and Its Application for Oral Squamous Cell Carcinoma.

    Shizuka Morodomi, Akiyuki Hirosue, Akhinur Rahman, Kyotaro Nohata, Misaki Matsuo, Omnia Reda, Samiul Alam Rajib, Haruki Saito, Hiroki Takeda, Ryoji Yoshida, Masafumi Nakamoto, Masatoshi Hirayama, Kenta Kawahara, Mitsuyoshi Takatori, Yorihisa Orita, Hideki Nakayama, Yorifumi Satou

    Cancer medicine   14 ( 4 ) e70544   2025.02 [ Peer Review Accepted ]

    Type of publication: Research paper (scientific journal)

     View Summary

    BACKGROUND: Virus-related cancers are malignancies caused by specific viruses, such as human papillomavirus (HPV), hepatitis B virus, and human T-cell leukemia virus, contributing significantly to the global cancer burden through persistent infection and oncogenic transformation. The current study aimed to develop a robust HPV-16 detection method for formalin-fixed cancer specimens. MATERIALS AND METHODS: To prevent false negatives resulting from DNA fragmentation, a DNA quality check step was added. Additionally, this study used multiplex polymerase chain reaction (PCR) covering the entire HPV-16 genome to mitigate effects caused by viral sequence variation. To prove this concept, we analyzed genomic DNA extracted from oropharyngeal cancer tissues known as HPV-16-positive. Subsequently, the protocol was tested on oral squamous cell carcinoma (OSCC) samples in our cohort. Given the wide variation in HPV-16 positivity in previous studies, it remains elusive how frequently HPV-16 is positive in OSCC. RESULTS: The results showed faint bands or smears in the multiplex PCR of 7 out of 112 cases. Droplet digital PCR confirmed variable positivity levels of HPV-16, suggesting two scenarios of HPV-16 positivity in cancer tissue: cancer cells derived from infected cells or only a portion being HPV-16-positive. Finally, we comprehensively analyzed the case and identified the integration of a deleted HPV-16 genome into the intronic region of the host gene TMEM94 on chromosome 17. To the best of our knowledge, this is the first evidence showing the integration of HPV-16 in OSCC cells and providing its complete viral sequence. CONCLUSIONS: The established protocol should be applicable to various cancer tissues for analyzing the association with HPV-16 infection.

  • Recent progress in pathological understanding of adult T-cell leukemia/ lymphoma in the new classification era

    Karube, K; Sakihama, S; Takatori, M; Morichika, K; Tamaki, T; Wada, N; Fukushima, T

    LEUKEMIA RESEARCH ( Leukemia Research )  148   107634 - 107634   2025.01 [ Peer Review Accepted ]

    Type of publication: Research paper (scientific journal)

     View Summary

    Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell lymphoma caused by Human T-cell leukemia virus type 1 (HTLV-1) infection. Although the 5th Edition of the WHO classification (WHO-5) did not make drastic changes regarding the disease concept of ATLL from the revised 4th Edition of the WHO classification (WHO-4R), WHO-5 newly introduced the essential and desirable diagnostic criteria, namely, "neoplastic lymphoid cell proliferation with mature T-cell phenotype; proven HTLV-1 carriership" and "identification of monoclonal integration of HTLV-1", respectively. To satisfy the desirable criteria, a new diagnostic method using a combination of HBZ-ISH and tax-PCR was introduced for the identification of the HTLV-1 in addition to the conventionally used Southern blot hybridization, especially in the case when only FFPE specimens are available. Morphologically, pleomorphic- and anaplastic large cell-type, account for most cases, while minor variants, ATLL with dermatopathic reaction, angioimmunoblastic T-cell lymphoma-like variant, and classic Hodgkin lymphoma-like variant, should also be noted as diagnostic pitfalls. Phenotypically, about 80 % of ATLL cases show a typical phenotype of CD3 + CD4 +CD25 +CCR4 + , while about 10 % show atypical phenotypes such as T follicular helper cell-like one. Many genetic abnormalities, mainly associated with the TCR signaling pathway, are observed, and most are more frequent in the aggressive type than in the indolent type, except for STAT3, indicating the heterogeneous pathogenic process of ATLL. In this review, we present the latest findings on molecular pathogenesis and histopathological findings of ATLL in the era of the new classification of lymphomas, serving as a basis for future research and classification.

  • Viral antigen mismatch affects antiviral T-cell response and may impair immunotherapeutic efficacy against adult T-cell leukemia/lymphoma

    Kenji Sugata, Mitsuyoshi Takatori, Omnia Reda, Benjy Jek Yang Tan, Masahito Tokunaga, Tomoo Sato, Mitsuharu Ueda, Yoshihisa Yamano, Atae Utsunomiya, Yorifumi Satou

    The Journal of Infectious Diseases ( Oxford University Press (OUP) )    2024.09 [ Peer Review Accepted ]

    Type of publication: Research paper (scientific journal)

     View Summary

    Abstract HTLV-1 transforms primary CD4+ T cells in vitro within a short time; however, majority of infected individuals maintain an asymptomatic condition, suggesting there is an equilibrium between the infected cells and the host immunity. In this study, we identified a variation in a major viral antigen epitope, HTLV-1 Tax301-309, in HLA-A24-positive individuals. Mismatch in A24/Tax301-309 multimers impaired detection of anti-Tax CTLs. Notably, over half of the TCRs of the anti-Tax CTLs did not recognize mismatched Tax301-309 peptides. These findings highlighted the importance of matching the viral antigen epitope type in T-cell-based immunotherapy against ATL by using viral antigen Tax.

  • A micro-disc-based multiplex method for monitoring emerging SARS-CoV-2 variants using the molecular diagnostic tool Intelli-OVI

    Md Belal Hossain, Yoshikazu Uchiyama, Samiul Alam Rajib, Akhinur Rahman, Mitsuyoshi Takatori, Benjy Jek Yang Tan, Kenji Sugata, Mami Nagashima, Mamiyo Kawakami, Hitoshi Ito, Ryota Kumagai, Kenji Sadamasu, Yasuhiro Ogi, Tatsuya Kawaguchi, Tomokazu Tamura, Takasuke Fukuhara, Masahiro Ono, Kazuhisa Yoshimura, Yorifumi Satou

    Communications Medicine     2024.08 [ Peer Review Accepted ]

    Type of publication: Research paper (scientific journal)

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Presentations 【 display / non-display

  • Tissue-specific mechanism and tumor heterogeneity in lymphoma-type ATL

    Mitsuyoshi Takatori

    HTLV Conference 2024  2024.06  -  2024.06 

  • Tissue-specific pathogenesis and tumor heterogeneity in lymphoma-type adult T-cell leukemia/lymphoma

    Mitsuyoshi Takatori

    24th Kumamoto AIDS Seminar  2023.11  -  2023.11 

  • Single-cell RNA-seq and spatial transcriptomics in lymph nodes of ATLL patients

    Mitsuyoshi Takatori

    25th Summer Retrovirus Conference  2023.07  -  2023.07 

  • Establishment of a novel diagnostic algorithm using biopsy specimens in adult T-cell leukemia/lymphoma

    Mitsuyoshi Takatori

    23rd Kumamoto AIDS Seminar  2022.10  -  2022.11 

Grant-in-Aid for Scientific Research 【 display / non-display

  • Grant-in-Aid for Scientific Research(C)

    Project Year: 2025.04  -  2028.03 

    Direct: 3,600,000 (YEN)  Overheads: 4,680,000 (YEN)  Total: 1,080,000 (YEN)

  • Grant-in-Aid for Young Scientists(B)

    Project Year: 2023.04  -  2025.03