Personal History Outline

Dr. Miura graduated from the Department of Biology of the Faculty of Science at Tokyo Metropolitan University (TMU) in 1983 and went on to study mRNA synthesis and its role in spore germination in the fern Cyathea spinulosa during his master’s course at TMU. In 1985, he started his investigations on the mechanisms of oligodendrocyte differentiation under the supervision of professor Katsuhiko Mikoshiba in the Division of Regulation of Macromolecular Function of the Institute for Protein Research, Osaka University, and the Division of Behavior and Neurobiology of the National Institute for Basic Biology. In 1988, he received his Ph.D. degree on the thesis titled: “Transcriptional regulation and promoter function of mouse myelin basic protein gene.” After receiving a postdoctoral fellowship from the Japan Society for the Promotion of Science, he was appointed instructor in the Department of Physiology at the Keio University School of Medicine in 1989. There, he worked with professor Keiichi Uyemura on the function of the cell adhesion molecule L1, an immunoglobulin superfamily protein, in neuronal cell migration. In 1992, under the supervision of assistant professor Junying Yuan, he started studying the molecular mechanisms of programmed cell death as a Fogarty International Research Fellow at the Massachusetts General Hospital (MGH). In 1995 and 1997, he successively became a lecturer in the Department of Molecular Neurobiology of the Institute of Basic Medical Sciences at the University of Tsukuba and an associate professor in the Department of Neuroanatomy of the Biomedical Research Center at Osaka University, where he started genetic studies of programmed cell death in Drosophila flies with professor Hideyuki Okano. In 2001, he became team leader of the Laboratory for Cell Recovery Mechanisms at the Brain Science Institute of The Institute of Physical and Chemical Research (RIKEN). In 2003, he was appointed professor in the Department of Genetics of the Graduate School of Pharmaceutical Sciences at the University of Tokyo. He was the principal investigator for the Core Research Project for Evolutional Science and Technology (CREST) titled “Genetic and Biochemical Study of Stress Responses Mediated by Metabolites” (2007-2012), granted by the Japan Science and Technology Corporation (JST), and the Advanced Research & Development Programs for Medical Innovation (AMED-CREST) titled “Mechanisms of Homeostatic Maintenance by Quorum Control of the Tissue in Whole Body” (2012-2017), granted by the Japan Agency for Medical Research and Development (AMED). In 2015, he was appointed Chair of the Board of Directors of the Japanese Society for Cell Death Research.

Academic Achievement

Cell-lineage tracing in the nematode Caenorhabditis elegans (C. elegans) revealed that exactly 131 cells underwent programmed cell death during development, while genetic studies showed that the ced-3 gene was required for the initiation of all these programmed cell death events. With his continued interest in cell death mechanisms, in 1993, Dr. Miura proved for the first time that C. elegans CED-3 protein and its mammalian homolog Caspase-1 (also known as Interleukin 1β-converting enzyme: ICE) shared a conserved function and could induce apoptosis, a form of programmed cell death, in mammalian cell cultures via their proteolytic activities. Dr. Miura’s group then went on to demonstrate the conservation of the apoptotic pathways in Drosophila and study the physiological roles of apoptosis. Their works were instrumental in establishing Drosophila as an ideal model organism to characterize the physiological roles of apoptosis via genetic studies.
Using a combination of live imaging and genetic studies, Dr. Miura’ group elegantly identified novel functions of apoptosis, including the elimination of developmental noise associated with mis-specified cells, the stimulation of cell proliferation by dying cells, age-induced impairments of attraction behavior and the induction of rapid changes in morphogen levels via the elimination of signaling center cells. Furthermore, they uncovered that caspases could function as regulatory molecules without inducing cell death.
Hence, Dr. Miura’s research was highly influential in both cell death and caspase research fields and provided new perspectives on the establishment and maintenance of tissues by apoptosis and caspases. His work, therefore, represents an essential contribution to the fields of developmental biology, basic medical research, and comparative oncology.

Bibliography (selected):

1. Miura, M., Zhu, H., Rotello, R., Hartweig, E. A., and Yuan, J.: Induction of apoptosis in fibroblasts by IL-1-β converting enzyme, a mammalian homolog of the C. elegans cell death gene ced-3. Cell 75, 653-660, 1993.
2. Wang, L., Miura, M., Bergeron, L., Zhu, H., and Yuan, J.: Ich-1, an Ice/Ced-3 related gene, encodes both positive and negative regulators of programmed cell death. Cell 78, 739-750, 1994.
3. Miura, M., Friedlander, R. M., and Yuan, J.: Tumor necrosis factor-induced apoptosis is mediated by a CrmA-sensitive cell death pathway. Proc. Natl. Acad. Sci. USA. 92, 8318-8322, 1995.
4. Wang, S., Miura, M., Jung, Y-K., Zhu, H., Li, E., and Yuan, J.: Murine caspase-11, an ICE interacting protease, is essential for activation of ICE. Cell 92, 501-509, 1998 (The first two authors contributed equally to this manuscript).
5. Kanuka, H., Sawamoto, K., Inohara, N., Matsuno, K., Okano, H., and Miura, M.: Control of cell death pathway by Dapaf-1, a Drosophila Apaf-1/CED-4 related caspase activator. Molecular Cell 4, 757-769, 1999.
6. Igaki, T., Kanuka, H., Inohara, N., Sawamoto, K., Nunez, G., Okano, H., and Miura, M.: Drob-1, a Drosophila member of the Bcl-2/CED-9 family that promotes cell death. Proc. Natl. Acad. Sci. USA 97, 662-667, 2000.
7. Igaki, T., Kanda, H., Yamamoto-Goto, Y., Kanuka, H., Kuranaga, E., Aigaki, T., and Miura, M.: Eiger, a TNF superfamily ligand that triggers the Drosophila JNK pathway. EMBO J. 21, 3009-3018, 2002.
8. Kanda, H., Igaki, T., Kanuka, H., Yagi, T., and Miura, M.: Wengen, a member of the Drosophila TNF receptor superfamily, is required for Eiger signaling. J. Biol. Chem. 277, 28372-28375, 2002.
9. Kuranaga, E., Kanuka, H., Igaki, T., Sawamoto, K., Ichijo, H., Okano, H., and Miura, M.: Reaper-mediated inhibition of DIAP1-induced TRAF1 degradation results in activation of JNK in Drosophila. Nature Cell Biol. 4, 705-710, 2002.
10. Takemoto, K., Nagai, T., Miyawaki, A., and Miura, M.: Spatio-temporal activation of caspase revealed by indicator that is insensitive to environmental effects. J. Cell Biol. 160, 235-243, 2003.
11. Kanuka, H., Kuranaga, E., Takemoto, K., Hiratou, T., Okano, H., and Miura, M.: Drosophila caspase transduces Shaggy/GSK-3β kinase activity in neural precursor development. EMBO J. 24, 3793-3806, 2005.
12. Kuranaga, E., Kanuka, H., Tonoki, A., Takemoto, K., Tomioka, T., Kobayashi, M., Hayashi, S., and Miura, M.: Drosophila IKK-related kinase regulates nonapoptotic function of caspases via degradation of IAPs. Cell 126, 583-596, 2006.
13. Kondo, S., Senoo-Matsuda, N., Hiromi, Y., and Miura, M.: Dronc coordinates cell death and compensatory proliferation. Mol. Cell. Biol. 26, 7258-7268, 2006.
14. Koto, A., Kuranaga, E., and Miura, M.: Temporal regulation of Drosophila IAP determines the dual functions of caspases in sensory organ development. J. Cell Biol. 187, 219-321, 2009.
15. Koto, A., Kuranaga, E., and Miura, M.: Apoptosis ensures spacing pattern formation of Drosophila sensory organs. Current Biol. 21, 278-287, 2011.
16. Nakajima, Y-I, Kuranaga, E., Sugimura, K., Miyawaki, A., and Miura, M.: Non-autonomus apoptosis is triggered by local cell cycle progression during epithelial replacement in Drosophila. Mol. Cell Biol. 31, 2499-2512, 2011.
17. Yamaguchi, Y., Shinotsuka, N., Nonomura, K., Takemoto, K., Kuida, K., Yoshida, H., and Miura, M.: Live imaging of apoptosis in a novel transgenic mouse highlights its role in neural tube closure. J. Cell Biol. 195, 1047-1060, 2011.
18. Takeishi, A., Kuranaga, E., Tonoki, A., Misaki, K., Yonemura, S., Kanuka, H., and Miura, M.: Homeostatic epithelial renewal in the gut is required to dampen a fatal systemic wound response in Drosophila. Cell Rep. 3, 919-930, 2013.
19. Nonomura, K., Yamaguchi, Y., Hamachi, M., Koike, M., Uchiyama, Y., Nakazato, K., Mochizuki, A., Sakaue-Sawano, A., Miyawaki, A., Yoshida, H., Kuida, K., and Miura, M.: Local apoptosis modulates early mammalian brain development through the elimination of morphogen producing cells. Developmental Cell 27, 621-634, 2013.
20. Obata, F., Kuranaga, E., Tomioka, K., Ming, M., Takeishi, A., Chen, C-H., Soga, T., and Miura, M.: Necrosis-driven systemic immune response alters SAM metabolism through the FOXO-GNMT axis. Cell Rep. 7, 821-833, 2014.
21. Liu, T., Yamaguchi, Y., Shirasaki, Y., Shikada, K., Yamagishi, M., Hoshino, K., Kaisho, T., Takemoto, K., Suzuki, T., Kuranaga, E., Ohara, O., and Miura, M.: Single-cell imaging of caspase-1 dynamics reveals an all-or-none inflammasome signaling response. Cell Rep. 8, 974-982, 2014.
22. Chihara, T., Kitabayashi, A., Morimoto, M., Takeuchi, K., Masuyama, K., Tonoki, A., Davis, R.L., Wang, J.W., and Miura, M.: Caspase inhibition in select olfactory neurons restores innate attraction behavior in aged Drosophila. PLOS Genetics 10, e1004437, 2014.
23. Obata, F., Tsuda-Sakurai, K., Yamazaki, T., Nishio, R., Nishimura, K., Kimura, M., Funakoshi, M., and Miura, M. Nutritional control of stem cell division through S-adenosylmethionine in Drosophila intestine. Developmental Cell 44, 741-751, 2018.
24. Fujisawa, Y., Kosakamoto, H., Chihara, T., and Miura, M.: Non-apoptotic function of Drosophila caspase activation in epithelial thorax closure and wound healing. Development 146, dev169037, 2019.