Tsuyoshi Hirashima

Research Assistant Professor, Mechanobiology Institute, National University of Singapore

 thira@nus.edu.sg
09-03-04
Level 9 T-Lab
National University of Singapore
5A Engineering Drive 1
Singapore 117411

Laboratory website
Multicellular Biophysics in Development and Reproduction

Affiliations
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore

Tsuyoshi Hirashima

Principal Investigator

Research Areas

Collective cell dynamics in mammalian development and reproduction, live cell imaging, mathematical modeling

Research Interests

Our group is interested in how collective cell behavior emerges and links with biological functions in development and reproduction. We focus on cellular mechano-chemical coupling regulations in mammalian tissues and explore design principles of multicellular dynamical systems.

We have studied how chemical cell signaling changes according to and regulates mechanical forces in multicellular tissues by combining fluorescence live-imaging and mathematical modeling. In particular, we used FRET cell imaging technique to detect kinase activity and clarified that extracelluar signal-regulated kinase (ERK) activity is mechano-sensitive and generates active cellular forces. These properties underpin collective epithelial migration (2020, Dev Cell; 2021, Nat Phys) and tissue morphogenesis in developing murine organs, such as tracheal and cochlear duct (2021, Front Cell Dev Biol; 2021, eLife). Moreover, we have proposed that the ERK-mediated mechano-chemical coupling depends on tissue curvature in the murine lung epithelium, which regulates recursive branching patterning (2021, bioRxiv). We will pursue this regulatory principle by integrating the 3D tissue geometry, to understand not only morphogenesis but also tissue homeostasis and repair.

Another aspect of our biological interest is reproduction. The origin and roles of germ cell dynamics in reproductive tracts remain less understood despite of their physiological importance (2022, Semin Cell Dev Biol). To better understand, we have used intravital microscopy for studying murine reproductive tracts, enabling us to observe the cellular and molecular activities in living mouse tissues (2021, Biol Reprod; 2022, Reproduction). Particularly, we will explore the biophysical mechanisms of how collective sperm dynamics emerge and link with reproductive functions.

Education

Ph.D. in Science, Kyushu University (2011)

Biography

Tsuyoshi Hirashima was trained as a mathematical biologist and received his Ph.D. from Kyushu University in 2011. During his Ph.D. training, he studied mathematical modeling on tissue morphogenesis in development under the mentorship of Prof. Yoh Iwasa. He moved to Kyoto University as a JSPS postdoc research fellow and learned experimental skills in cell and developmental biology at Prof. Ryoichiro Kageyama’s lab. He then joined the faculty of Kyoto University as an Assistant Professor in 2014, a senior lecturer in 2017, and an Associate Professor at the Hakubi Center for Advanced Research in 2021. He has since joined MBI in 2022 to further pursue his scientific and personal curiosity. He has been on the editorial board of Journal of Theoretical Biology since 2022.

Recent Publications (selected)

1. Chii Jou Chan* and Tsuyoshi Hirashima*
   Tissue hydraulics in reproduction.
   Seminars in Cell and Developmental Biology, 2022.
2. Yuta Kanazawa, Takuya Omotehara*, Hiroki Nakata, Tsuyoshi Hirashima, Masahiro Itoh
   Three-dimensional analysis and in vivo imaging for sperm release and transport in the murine seminiferous tubule.
   Reproduction, 164, pp9-18, 2022.
3. Tsuyoshi Hirashima*
   Live imaging approach of dynamic multicellular responses in ERK signaling during vertebrate tissue development.
   Biochemical Journal, 479, pp129-143, 2022.
4. Mamoru Ishii, Tomoko Tateya, Michiyuki Matsuda, Tsuyoshi Hirashima*
   Retrograde ERK activation waves drive base-to-apex multicellular flow in murine cochlear duct morphogenesis.
   eLife, 10:e61092, 2021.
5. Mamoru Ishii, Tomoko Tateya, Michiyuki Matsuda, Tsuyoshi Hirashima*
   Stalling interkinetic nuclear migration in curved pseudostratified epithelium of developing cochlear duct.
   Royal Society Open Science, 8:211024, 2021.
6. Daiki Hashimoto, Tsuyoshi Hirashima*, Hisao Yamamura, Tomoya Kataoka, Kota Fujimoto, Taiju Hyuga, Atsushi Yoshiki, Kazunori Kimura, Shunsuke Kuroki, Makoto Tachibana, Kentaro Suzuki, Nobuhiko Yamamoto, Takehiko Sasaki, Gen Yamada*.
   Dynamic erectile responses of a novel penile organ model utilizing two-photon excitation microscopy.
   Biology of Reproduction, 104, 4, pp875-886, 2021.
7. Daniel Boocock#, Naoya Hino#, Natalia Ruzickova, Tsuyoshi Hirashima*, Edouard Hannezo* (#equally contributed)
   Theory of mechano-chemical patterning and optimal migration in cell monolayers.
   Nature Physics, 17, pp267–274, 2021.
8. Naoya Hino, Leone Rossetti, Ariadna Marín-Llauradó, Kazuhiro Aoki, Xavier
   Trepat, Michiyuki Matsuda*, Tsuyoshi Hirashima*
   ERK-mediated mechanochemical waves direct collective cell polarization.
   Developmental Cell, 53, 6, pp646-660, 2020.
9. Takuya Yoshida, Michiyuki Matsuda, Tsuyoshi Hirashima*
   Incoherent feedforward regulation via Sox9 and ERK underpins mouse tracheal cartilage development.
   Frontiers in Cell and Developmental Biology, doi: 10.3389/fcell.2020.585640, 2020.
10. Tsuyoshi Hirashima* and Taiji Adachi
    Polarized Cellular Mechanoresponse System for Maintaining Radial Size in Developing Epithelial Tubes.
    Development, 146:dev181206, 2019.