Welcome to Molecular Physiological Chemistry Lab!

60240533 縣 保年 Prof. Yasutoshi Agata

Our research focuses on how cancer cells are developed and how our immune cells fight against cancers. We are currently conducting three projects described below.

  • 1) Regeneration of T cells that fight against cancers from iPS cells

In cancer immunotherapies, it is difficult to propagate tumor-specific T cells from cancer patients. To overcome this problem, we have tried to regenerate T cells that can fight against cancers from iPS cells in collaboration with Dr. Hiroshi Kawamoto in Kyoto Univ, who made iPS cells from tumor-specific T cells (T-iPSCs) and then regenerate T cells from the T-iPSCs(Cell Stem Cell 12: 31, 2013). We are currently developing methods to regenerate T cells efficiently and rapidly by introducing tumor-specific T-cell receptor (TCR) genes into iPSCs using genome editing.

  • 2) Development of macaque cancer models and cloning tumor-specific TCR genes

To evaluate the efficacy of cancer immunotherapies, we need primate animal models because rodent models are different from primate cases. We have thus tried to develop macaque models in which cancer-promoting genes are inducibly expressed. We have concurrently used another macaque model in which cancer cells are transplanted into MHC-matched animals. We cloned TCR genes from single tumor-infiltrating lymphocytes (TIL) and successfully identified TCR genes which can kill cancer cells upon introduction in T cells.

  • 3) Investigation of super-enhancer functions in cancer development

In cancer cells, cancer-promoting genes are highly expressed by the formation of super-enhancers, large clusters of enhancers. To elucidate the function of super-enhancers in cancer development, we investigate how super-enhancers are formed using inhibitors of super-enhancer-associated factors and how these factors function to activate transcription of cancer-promoting genes by using live-cell imaging.

140717 本庶先生cut with Drs. Tasuku Honjo and Yasumasa Ishida