Molecular Innate Immunity and Trained Innate Immunity
Department of Chemistry, Organic and Biological Chemistry
Understanding 1) the molecular mechanisms of differentiation and maturation of innate immune cells, 2) the roles of Ser/Thr phosphatase PPM1D in innate immunity
|Field||Biological Chemistry, Peptide Science, Bio-related Chemistry, Cell Biology, Functional Biochemistry|
|Keyword||Protein, Peptide, Cell Differentiation, Enzyme, Innate Immunity, Trained Innate Immunity, Neutrophils|
Introduction of Research
Chromatin provides major mechanisms of epigenetic regulation in mammals. Aberrant epigenetic regulation is frequently associated with diseases including cancer, immune disease. Interferons (IFN) are produced after viral or bacterial infection and inflammatory signals. In mammals, IFN provide the first line of defense against pathogens. IFNs stimulate transcription of more than 1,500 genes that are called IFN stimulated genes (ISGs). We found that the fibroblasts that had been stimulated IFN earlier were able to induce ISGs faster and at higher levels when they were restimulated by IFN. This process was regulated with a distinct chromatin state involving the histone H3.3 and H3K36 modifications (Fig.1). Our findings provide mechanistic framework for “trained innate immunity”.
We are also studying the role of Ser/Thr phosphatase PPM1D in regulation of immune cell differentiation and maturation. We are developing PPM1D selective inhibitors and new analysis techniques and tools for monitoring cell differentiation. The goal of our research is to understand the molecular mechanisms that regulate innate immune responses and trained innate immunity.
Kamada, R., Yang, W., Zhang, Y., Patel, M.C., Yang, Y., Ouda, R., Dey, A., Wakabayashi, Y., Sakaguchi, K., Fujita, T., Tamura, T., Zhu, J., and Ozato, K.
Proc. Natl. Acad. Sci. U.S.A. 2018, 115, E9162-E9171.
Kamada, R.*, Kudoh, F., Yoshimura, F., Tanino, K., and Sakaguchi, K.
J. Biochem. 2017, 162, 303-308.
Kozakai, Y.*, Kamada, R.*, Furuta, J., Kiyota, Y., Chuman, Y., and Sakaguchi, K.
Sci. Rep. 2016, 6, 31993.
Kamada, R., Tano, F., Kudoh, F., Kimura, N., Chuman, Y., Osawa, A., Namba, K., Tanino, K., and Sakaguchi, K.
PLoS One, 2016, 11, e0160625
Ogasawara, S., Kiyota, Y., Chuman, Y., Kowata, A., Yoshimura, F., Tanino, K., Kamada, R., and Sakaguchi, K.
Bioorg. Med. Chem. 2015, 23, 6246-6249.
|Academic background||2006 B.Sc. Hokkaido University, Sapporo, Japan|
2007 M.Sc. Hokkaido University, Sapporo, Japan
2010 Ph.D. Hokkaido University, Sapporo, Japan
2008-2011 Research Fellow of the Japan Society for the Promotion of Science (DC1)
2011-2012 Postdoctral Fellow, Kyoto University, Kyoto, Japan
2012-2014 Visiting Fellow, National Institutes of Health, MD, USA
2014- Assistant Professor, Hokkaido University, Sapporo Japan
|Affiliated academic society||The Japanease Biochemical Society, The Chemical Society of Japan, The Japanease Peptide Society, Japanease Association for Protein Phosphatase Research|
|Room address||Science Building 6 Room 6-507|