Medical Sciences Group/Core LaboratoriesYamagishi Laboratory
(Laboratory of Viral Oncology and Genomics)

Laboratory of Viral Oncology and Genomics is a new laboratory launched in April 2023. With the spread of various cancers and infectious diseases in the world, there is a renewed awareness of the importance of basic research to deepen our understanding of hosts and pathogens. We are conducting research by integrating various academic disciplines centered on molecular biology, genomic medicine, and data science, aiming to develop new therapeutic and diagnostic methods for viral infected diseases and hematological malignancies through genomic and epigenomic studies.

Genome, Epigenome, HTLV-1, Retrovirus, Hematological malignancy
(1) Research on the mechanism of virus-induced tumorigenesis

Some viruses cause serious cancers after a chronic latent period. Our research goal is to elucidate the mechanism of tumorigenesis caused by human retroviruses such as Human T cell Leukemia Virus type I (HTLV-1) and Epstein-Barr virus (EB virus). We are studying adult T cell leukemia-lymphoma (ATL), HTLV-1-associated myelopathy (HAM/TSP), and EB virus-associated diseases. We also study the molecular pathogenesis and latency of other hematological malignancies and HIV-1-induced AIDS. We are working on experimental medicine and data science, introducing technologies such as next-generation sequencing and single-cell analysis for clinical specimens. We aim to elucidate the pathological mechanism from clinical big data and disseminate new information that will lead to early diagnosis, prevention of disease onset, and development of new therapeutic strategies.

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

The epigenome is "the spatial regulation of genetic information," which is influenced from age and environmental effects. We have shown that retrovirus infection dramatically alters host cells' epigenome (histone modifications, DNA methylation, and chromatin structure). This mechanism is a critical host change imprinted by a viral infection and is directly involved in molecular pathogenesis and cell fate control. We are focusing on the characteristics, diversity, and plasticity of the aberrant epigenome formed in cancer and infectious diseases and are working to decipher the "epigenomic code".

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

Clonal evolution refers to the formation of subclones by the random occurrence of genetic and epigenetic abnormalities in a common cell (clone), which are then subjected to natural selection and evolution under Darwin's theory. How do cancers evolve and adapt over time while acquiring diversity within individuals? This difficult challenge is critical to understand the development and progression of cancer. We are interested in the mechanisms of clonal evolution of diverse infected cell populations formed by precancerous conditions and viral infections, leading to disease. In order to accurately analyze diverse cell populations, we entirely use deep sequencing and single-cell analysis techniques.

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

Basic research leads to the development of new therapeutic and diagnostic methods. Through epigenomic studies of malignant lymphoma and virus-infected cells, we have identified two molecules, EZH1 and EZH2, that cause chromatin aggregation aberrantly. We have successfully developed new epigenetic drugs that inhibit EZH1/2 in collaboration with a pharmaceutical company (Nature 2024). This research achievement had a great impact as a new epigenomic therapy for intractable diseases and taught us how important it is to conduct basic research on molecular pathogenesis using clinical specimens and disease models. We focus and research on new therapeutic drug development studies.

(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.

  • References:
  • Yamagishi et al., Cancer Cell, 21, 121-135, 2012
  • Fujikawa et al., Blood, 127, 1790-1802, 2016
  • Yamagishi M and Uchimaru K. Curr. Opin. Oncol. 29, 375-381, 2017.
  • Yamagishi et al., Cell Rep., 29, 2321-2337, 2019
  • Nagasaka et al., Proc. Natl. Acad. Sci. U S A., 17, 11685-11691, 2020.
  • Yamagishi et al., Nat Commun. 12, 4821, 2021
  • Yamagishi et al., Nature. 627, 221-228, 2024
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