(1) Research on the mechanism of virus-induced tumorigenesis

Some viral infections can lead to aggressive cancers after a prolonged latent period. We investigate oncogenic mechanisms driven by human T-cell leukemia virus type 1 (HTLV-1) and Epstein–Barr virus (EBV), focusing on adult T-cell leukemia/lymphoma (ATL), HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP), and EBV-associated diseases. We also study other hematologic malignancies (leukemias and malignant lymphomas) and the molecular pathogenesis and latency of HIV-1 infection. Leveraging next-generation sequencing (NGS) of clinical specimens and single-cell technologies, we advance our work through both experimental medicine and data science. Building on clinical big data and integrative omics, we aim to translate mechanistic insights into early diagnosis, disease prevention, and the development of novel therapies.

(2) Decoding the epigenetic code of cancer and infectious diseases

The epigenome is the regulatory layer that governs how genomic information is used, and it changes dynamically with age and environmental cues. We have shown that retroviral infection extensively rewires the host-cell epigenome—encompassing histone modifications, DNA methylation, and chromatin architecture. These alterations constitute durable host imprints of infection that directly influence disease mechanisms, molecular pathology, and cell-fate control. We are currently dissecting the features, heterogeneity, and plasticity of aberrant epigenomes arising in cancer and infectious disease, with the goal of deciphering a shared “epigenomic code” of viral infection and oncogenesis.

(3) Research on clonal evolution of cancer and infectious diseases

Clonal evolution refers to the process in which stochastic accumulation of genomic alterations and epigenomic changes within a common ancestral clone gives rise to branching subclones that adapt and expand under natural selection. A central question is how cancers, over many years within an individual, acquire diversity and evolve to adapt. Answering this directly advances our understanding of tumor initiation and progression and informs the development of diagnostic and therapeutic strategies.
We investigate the mechanisms by which cell populations in precancerous states and virus-infected cell populations undergo clonal evolution to disease. To resolve this diversity at high resolution, we employ high-depth sequencing and single-cell analyses to reconstruct evolutionary trajectories and delineate the selection pressures that shape them.

(4) Research on new therapeutic drug development using data science

Breakthroughs in basic research pave the way for new diagnostics and therapies. Through epigenomic analyses of malignant lymphomas and virus-infected cells, we identified EZH1 and EZH2—H3K27 methyltransferases that drive chromatin compaction—as actionable targets, and, in industry–academia collaboration, co-developed a dual EZH1/2 inhibitor (Yamagishi et al., Nature, 2024). This achievement not only highlights the promise of epigenome-targeted therapy for refractory diseases, but also underscores the central importance of foundational studies using clinical specimens and disease models to elucidate molecular pathogenesis and disease initiation. Going forward, we will continue to couple fundamental biology with data science to accelerate therapy-oriented drug discovery.

(5) Research on various infectious diseases (Collaboration with UTOPIA, The University of Tokyo)

In collaboration with the The University of Tokyo Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA), we are conducting basic research (immunology, host-virus interactions, viral genome evolution, epidemiology, etc.) on a variety of infectious diseases. If you are interested in studying infectious disease research in graduate school, please contact us.