Researcher Information


Associate Professor

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

FieldBiological Chemistry, Peptide Science, Bio-related Chemistry, Cell Biology, Functional Biochemistry
KeywordProtein, Cell Differentiation, Phosphatase, Innate Immunity, Trained Innate Immunity, Neutrophils, Peptide

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.

Transcriptional Memory in Innate Immune Responses

Representative Achievements

InterferonInterferon stimulation creates chromatin marks and establishes transcriptional memory.
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.
Inhibition of Ser/Thr phosphatase PPM1D induces neutrophil differentiation in HL-60 cells.
Kamada, R.*, Kudoh, F., Yoshimura, F., Tanino, K., and Sakaguchi, K.
J. Biochem. 2017, 162, 303-308.
PPM1D controls nucleolar formation by up-regulating phosphorylation of nucleophosmin.
Kozakai, Y.*, Kamada, R.*, Furuta, J., Kiyota, Y., Chuman, Y., and Sakaguchi, K.
Sci. Rep. 2016, 6, 31993.
Effective Cellular Morphology Analysis for Differentiation Processes by a Fluorescent 1,3a,6a-Triazapentalene Derivative Probe in Live Cells.
Kamada, R., Tano, F., Kudoh, F., Kimura, N., Chuman, Y., Osawa, A., Namba, K., Tanino, K., and Sakaguchi, K.
PLoS One, 2016, 11, e0160625
Novel Inhibitors Targeting PPM1D Phosphatase Potently Suppress Cancer Cell Proliferation.
Ogasawara, S., Kiyota, Y., Chuman, Y., Kowata, A., Yoshimura, F., Tanino, K., Kamada, R., and Sakaguchi, K.
Bioorg. Med. Chem. 2015, 23, 6246-6249.

Related industries

Academic degreePh.D.
Academic background2006 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 Postdoctoral Fellow, Kyoto University, Kyoto, Japan
2012-2014 Visiting Fellow, National Institutes of Health, MD, USA
2014-2020 Assistant Professor, Hokkaido University
2020- Associate Professor, Hokkaido University
Affiliated academic societyThe Japanease Biochemical Society, The Chemical Society of Japan, The Japanease Peptide Society, Japanease Association for Protein Phosphatase Research
Room addressScience Building 6 Room 6-507

Department of Chemistry, Organic and Biological Chemistry


Associate Professor

What is the research theme that you are currently focusing on?

The immune system which protects us against pathogenic microorganisms and cancer, rests on two types: the innate and the adaptive immune system. I am doing research to understand how various types of innate immune cells are differentiated from the hematopoietic stem cells and how these cells regulate their functions. I am focusing on the phosphatases, which catalyze the chemical reaction of dephosphorylation of the proteins in the functional regulation of neutrophils, first line of innate immune cells.

Ser/Thr phosphatase PPM1D regulates various cellular events
What made you decide to become a researcher?

When I was a child, I liked science the best. My parents often took me to a science museum and I really enjoyed it. When I was an undergraduate student, I met the research field of Biochemistry. Since then, I am immersed in the research studying functions of cells and proteins that work in living organisms. While pursuing my favorite research during undergraduate and graduate school years, I chose to be a scientist.

Please tell us about yourself; things you are good at, your favorites, hobbies, and daily routines.

Since I am from Hokkaido, I enjoy skiing in the winter. Hokkaido, the north island of Japan, is great area for skiing and snowboarding. I also love watching movies and baseball games.

Ski resort in Sapporo