Department of Physiology & Systems Bioscience
We are primarily interested in the fundamental basis of Circadian Rhythms in humans and all living organisms. Discrepancy between environmental time and the body clock is known to disrupt circadian rhythms and affect our health in various ways. The study of emergence, maintenance, and misalignment of circadian rhythms will unveil the mechanisms of disease development caused by environmental factors prevalent in our 24/7 modern societies. We aim to elucidate the basic principles of chronobiology and solve real-world problems associated with dysregulated circadian rhythms.
01Biological clock and circadian rhythm
We have recently illuminated that the biological clock is not present in pluripotent stem cells such as ES cells and iPS cells, but emerges in conjunction with the development and cell differentiation (PNAS, 2010). In addition, we also found that the formation of the biological clock is accompanied by synchronous adaptation to the environmental rhythms of the outside world (maternal rhythms) (PNAS, 2017). These findings suggest that the circadian clock interface the external environment and the internal physiology, creating an operational time order in the body in relation to the environment. Interestingly, we further discovered the transition of two different types of rhythms during the developmental process, from the segmentation clock to the circadian clock (PNAS, 2022). During somitogenesis, circadian clock-mediated 24-hour temporal order is suppressed to avoid interfere with the segmentation clock. Building on these recent findings, our current goal is to elucidate the principle of circadian rhythms and the control mechanism of homeodynamics that permeates the hierarchy of molecular, cellular, tissue, organ, and individual levels.
02Circadian rhythm disorder as pre-symptomatic disease
Since shift workers are indispensable for our society, the pressing challenge is to understand how exactly the environmental factors, such as deviations in lifestyle and body clocks, affect physiological functions and alter molecular and cellular mechanisms. The mechanism of homeostasis disruption due to environmental challenges is largely unclear, partly due to the significant barrier of individual differences. Recently, we succeeded in developing a new approach named "mouse cohort model" to deduce the progressive process of circadian disorders. We showed that circadian misalignment mimicking the shift work resulted in profound deleterious consequences in mice, leading to disrupted homeostasis and abbreviated lifespan (Sci Rep, 2020). We are now working to answer the question of how environmental perturbation initiates the sequence of events leading to circadian disorders.
03Human circadian physiology: From Lab to Society
Publication List (Selected)