Basic Medicine, Molecular and Cellular Biology
We Investigate the Functional Roles of Physical Forces in Development and Homeostasis to Discover New Therapeutic Approaches
Medical Sciences Course
- Master / Doctoral Degree
- OGURA, Toshihiko
Professor, M.D. Ph.D.
ogura*idac.tohoku.ac.jp (Please convert "*" into "@".)
- Mechano-transduction system that converts physical stimuli into biochemical/genetic responses
- Development of exercise pills based on the novel mechano-transduction pathways
- Mechanical regulation of metabolism and organogenesis
physical forces, gene expression, exercise pill (exercise mimetics), regulation of metabolism, force-sensing proteins
mechanical manipulation, gene knock-out, molecular biology
Physical forces regulate various aspects of embryogeneis and homeostasis, as embodied by massive bone atrophy of astronauts and bedridden patients. Molecular mechanism by which living cells sense physical forces and convert them into biochemical responses is largely unknown.
We have discovered several force-sensitive factors and are exploring the mechanism of signal transduction (mechano-transduction) triggered by the mechanical stimuli. Interestingly, we found that these factors regulate various processes of development, such as cardiogenesis and bone formation. More importantly, energy metabolism, regeneration and wound healing are under the control of the force-sensitive factors. This indicates that these factors are good targets of therapeutic drugs. Adopting physics and engineering techniques, we are exploring a new field of biology, in a hope of discovering new drugs and therapies.
Figure 1. Haemodynamics-dependent valvuloganesis.
- Inoue S et al., New BRAF knockin mice provide a pathogenetic mechanism of developmental defects and a therapeutic approach in cardio-facio-cutaneous syndrome. Hum Mol Genet. 23, 6553-6566, 2014
- Akira et al., Introducing Micrometer-Sized Artificial Objects into Live Cells: A Method for Cell-Giant Unilamellar Vesicle Electrofusion. PLoS ONE 9, e106853. doi; 10.1371/journal.pone.0106853, 2014
- Aoki Y. et al., Gain-of-Function Mutations in RIT1 Cause Noonan Syndrome, a RAS/MAPK Pathway Syndrome.The American Journal of Human Genetics, 93, 173-180, 2013.
- Banjo T. et al., Haemodynamically dependent valvulogenesis of zebrafish heart is mediated by flow-dependent expression of miR-21. Nature Communications, 4, Article number 1978, 2013 (doi:10.1038/ncomms2978).
- Watanabe Y. et al., Fibroblast growth factor 10 gene regulation in the second heart field by Tbx1, Nkx2-5, and Islet1 reveals a genetic switch for down-regulation in the myocardium. Proc Natl Acad Sci U S A. 109, 18273-18280, 2012