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Hiroshi Hamada

Distinguished Visiting Professor of Biology, Ashoka University

Hiroshi Hamada has studied how the body is correctly formed in vertebrate embryos, in particular, how left-right asymmetry of the body is created. Since the discovery of the asymmetric gene Lefty in 1995, he dissected and clarified the genetic pathway governing left-right asymmetry, from the symmetry breaking, differential patterning of left and right sides by secreted signals and finally to organ formation.

Hiroshi was a team leader at RIKEN Biosystems Dynamics Research until March 2023, but has moved to India as Distinguished Visiting Professor in Ashoka University and Visiting Professor in National Centre for Biological Sciences. Born in Japan, he initially studied medicine but was later trained as a cancer cell biologist through 5 years of post-doc in National Institute of Health, USA. He began to study cell differentiation of embryonal carcinoma cells when he became assistant professor in Newfoundland, Canada. He eventually returned to Japan in 1988 and stayed in Osaka University until 2017 where he studied developmental biology. Hiroshi was elected to Associate Member of the European Molecular Biology Organization in 2016 and to Foreign Member of the Royal Society in 2022, and was awarded the Keio Medical Science Prize in 2014.

Our body looks left-right (L-R) symmetric from outside, but visceral organs are L-R asymmetric in terms of their shape, position and size. He is interested in how L-R asymmetry is established during development in various animals including vertebrates and invertebrates.

L-R asymmetry of the body is established early during development. Breaking of L-R symmetry in fish, frog and mouse takes place at the region of the embryo called the left-right organizer (LRO) and involves uni-directional fluid flow generated by motile cilia at the LRO. In the last 10 years, his lab studied how embryos sense the fluid flow. The LRO of mouse embryos possesses another type of cilia, immotile cilia located at its periphery, which sense mechanical force generated by the fluid flow. When immotile cilia sense the flow, Ca2+enters the cell, and stimulates degradation of the target Dand5 mRNA. This Dand5 mRNA degradation occurs only on the left side, generating a molecular asymmetry in the embryo for the first time.

While his lab focused on L-R asymmetry in the mouse, various animals employ different strategies for generating L-R asymmetry. For example, unlike mouse, reptiles and birds break L-R asymmetry without cilia and fluid flow. In snail, L-R symmetry breaking is done at a very early stage, 2nd-3rd cell division, by a mechanism involving actin. However, the later step of L-R asymmetry employs the same set of genes Nodal and Pitx2. Currently his group is interested in studying how chick embryos break L-R symmetry without cilia and fluid flow. His team also studies snail embryos, how the non-conserved symmetry breaking event is connected  to the conserved asymmetric expression of Nodal-Pitx2. Molecular origin of morphological asymmetries is also a very interesting topic.

  • Hiver S, Shimizu-Mizuno N, Ikawa Y, Kajikawa E, Sai X, Nishimura H, Takaoka K, Nishimura O, Kuraku S, Tanaka S, Hamada H.*(2023). Gse1, a component of the CoREST complex, is required for placenta development in the mouse. Dev. Biol. doi: 10.1016/j.ydbio.2023.03.009.
  • Katoh, A. T.*, Omori, T.*, Mizuno, K., Sai, X., Minegishi, K., Ikawa, Y., Nishimira, H., Itabashi, T., Kajikawa, E., Hiver, S., Iwane, A., Okada, Y., Nishizaka, T. and Hamada, H. * (2023). Immotile cilia mechanically sense the direction of fluid flow for left-right determination. Science.379: 66-71. doi: 10.1126/science.abq8148.

  • Kajikawa, E., Miki, T., Takeda, M., Kiyonari, H. and Hamada, H. * (2022). Left-Right Asymmetric Expression of the Nodal-Lefty-Pitx2 Module in Developing Turtle Forebrain. Front. Cell Dev. Biol. 10:929808. doi: 10.3389/fcell.2022.929808.

  • Sai, X., Ikawa, Y., Nishimura, H., Mizuno, K., Kajikawa, E., Shiratori, H., Takaoka, K., Hamada, H.* and Minegishi, K. (2022). Planar cell polarity-dependent asymmetric organization of microtubules for polarized positioning of the basal body in node cells. Development 149(9) dev200315. doi: 10.1242/dev.200315.

  • Minegishi, K., Rothe, B., Komatsu, K.R., Ono, H., Ikawa, Y., Nishimura, H., Kato, T.A., Kajikawa, E., Sai, X., Miyashita, E., Takaoka, K., Bando, K., Kiyonari, H., Yamamoto,T., Saito, H.*, Constam, D.*, and Hamada, H.* (2021). Flow-induced decay of Dan5 mRNA for left-right symmetry breaking involves Bicc1-Ccr4 RNA degradation complex. Nat. Communic. 12:4071. doi: 10.1038/s41467-021-24295-2.

  • Mizuno, K.*, Shiozawa, K., Katoh, A. Minegishi, K., Ide, T., Ikawa, Y., Nishimura, H., Takaoka, K., Itabashi, T., Iwane, A., Nakai, J., Shiratori, H. and Hamada, H.* (2020). Role of asymmetric Ca2+ transients at the node of the mouse embryo in left-right symmetry breaking. Science Adv. 6:eaba1195. doi: 10.1126/sciadv.aba1195.

  • Kajikawa, E., Horo, Ide, T., Mizuno, K., Minegishi K., Hara, Y., Ikawa Y., Nishimura H., Uchikawa, M., Kiyonari, H., Kuraku Y.*, and Hamada, H.* (2020) Nodal paralogues underlie distinct mechanisms for visceral left–right asymmetry in reptiles and mammals. Nature Ecol. Evol. 4(2):261-269. doi:10.1038/s41559-019-1072-2

Study at Ashoka

Study at Ashoka