Research Area

• Biochemistry and molecular cell biology

Research Subjects

• Functions and molecular mechanisms of mechanical responses
• Molecular mechanisms of stress responses

Overview of Research

We are investigating the molecular mechanisms involved in the body’s response to environmental stresses, including mechanical forces and energy stresses. It is well known that muscles and bones are properly maintained by exercise and other forces, and that blood vessels physiologically respond to shear stresses caused by blood flow. Furthermore, mechanical responses in epithelial cells are also involved in morphogenesis of epithelial tissues.

In our study of mechanical responses, we are examining molecular mechanisms of the actin cytoskeleton and intermediate filament reorganization following application of mechanical stresses. In particular, we focus on the spatio-temporal regulation activities of Rho small G proteins in the intermediate filaments.

Molecular mechanisms of cellular response to energy stresses, such as hypoxia and limitation of glucose, are important in the control of apoptosis. Under hypoxic conditions, a large number of genes are induced by hypoxia inducible factors (HIFs) to facilitate adaptations to the low-oxygen environment. Prolyl hydroxylase domain-containing proteins (PHDs) regulate the amount of the HIFs in response to oxygen levels. Therefore, PHDs act as an oxygen sensor. Our recent research has identified novel roles of PHDs in the intracellular signaling pathway of stress responses. We focus on the crosstalk between hypoxia response and other signaling pathways.

Selected Publications

• Ninomiya K., Ohta K., Yamashita K., Mizuno K., Ohashi K.
  PLEKHG4B enables actin cytoskeletal remodeling during epithelial cell-cell junction formation.
  J. Cell Sci. 134, jcs249078 (2021)
• Isozaki Y., Sakai K., Kohiro K., Kagoshima K., Iwamura Y., Sato H., Rindner D., Fujiwara S., Yamashita K., Mizuno K., Ohashi K.
  The Rho-guanine nucleotide exchange factor Solo decelerates collective cell migration by modulating the Rho-ROCK pathway and keratin networks.
  Mol. Biol. Cell, 31: 741-752 (2020)
• Fujiwara, S., Ohashi, K., Mashiko, T., Kondo, H., Mizuno, K.
  Interplay between Solo and keratin filaments is crucial for mechanical force-induced stress fiber reinforcement.
  Mol. Biol. Cell, 27: 954-966 (2016)
• Abiko H., Fujiwara S., Ohashi K., Hiatari R., Mashiko T., Sakamoto N., Sato M., and Mizuno K.
  Rho-guanine nucleotide exchange factors involved in cyclic stretch-induced reorientation of vascular endothelial cells.
  J. Cell Sci. 128: 1683-1695 (2015)
• Hiwatashi Y, Kanno K, Takasaki C, Goryo K, Sato T, Torii S, Sogawa K, Yasumoto K.
  PHD1 interacts with ATF4 and negatively regulates its transcriptional activity without prolyl hydroxylation.
  Exp. Cell Res., 317: 2789-2799 (2011)

Contact Information

“Please delete “/” after “@” in a mail address.”
Kazumasa Ohashi
(TEL +81-22-795-6590, Email: kazumasa.ohashi.b2@/tohoku.ac.jp)
Ken-ichi Yasumoto
(TEL 022-795-6591, Email: ken-ichi.yasumoto.d8@/tohoku.ac.jp)

Website
http://www.biology.tohoku.ac.jp/lab-www/ohashi_lab/