Shinya Sakaguchi/Division of Immunobiology
Research interest
CD8+ T cells play a central role during immune responses against virus, intracellular bacteria and protozoan parasites and also key regulators of anti-tumor immunity. The main research topic of my group is to understand the molecular mechanisms controlling the differentiation of peripheral CD8+ T cells, particularly focusing on transcriptional and epigenetic regulations. Our ongoing/planned projects include:
- Investigation of the role of the zinc-finger protein MAZR/PATZ1 and its interactors for memory T cell differentiation
- Elucidation of the function of histone deacetylases for T cell exhaustion
- Identification of novel transcriptional/epigenetic regulators controlling the generation of memory T cells
In order to address these research questions, we employ multi-color flow-cytometry, next generation sequencing, mouse viral infection and tumor models, biochemical/molecular approaches, retroviral-mediated gene transduction and CRISPR-mediated gene knockout in primary mouse CD8+ T cells.
Schematic figure summarizing our research projects. Upon acute infection or vaccination CD8+ T cells differentiate into effector T cells and later form several memory T cell subsets, whereas chronic infection or cancer leads to the generation of “exhausted” T cells which also consist of heterogenous subsets. Our group aim to elucidate the network of transcriptional and epigenetic regulators governing CD8+ T cell subset differentiation during various immune responses. (part of illustration was taken from McLane et al., Annu Rev Immunol. 2019)