Sleep remains one of the greatest remaining mysteries. At the Sleep 2012 conference, we conceived a shift from the concept of “sleep substances” to “wake substances” such as calcium, suggesting that sleep homeostasis may arise from the integration of wake-related activity. Inspired by Dr. Setsuro Ebashi’s work on calcium signaling, we investigated calcium’s role in sleep regulation.

Using our Triple-CRISPR method (Sunagawa et al. 2016), we screened 25 genes related to calcium channels and pumps, revealing calcium as a brake on brain activity to promote sleep (Tatsuki et al. 2016). We also developed a tissue-clearing method CUBIC (Susaki et al. 2014; Tainaka et al. 2014) to visualize calcium’s effects on neural circuits. Further work showed that calcium-dependent enzymes, CaMKIIα/β kinases, act as calcium “memory” devices, with phosphorylation sites controlling sleep onset, duration, and termination (Tone et al. 2022). Other direct and indirect calcium-dependent phosphatases, Calcineurin and PP1 (sleep-promoting), and opposing kinases, PKA (wake-promoting), function as synaptic sleep switches (Wang et al. 2024).

We also identified the ryanodine receptor 1, a calcium channel, as a molecular target of inhalational anesthetics, hinting at shared pathways between anesthesia and sleep (Kanaya et al. 2025). Lastly, we proposed the WISE (Wake Inhibition Sleep Enhancement) mechanism, where quiet wakefulness suppresses and deep sleep strengthens synaptic connections, explaining links between sleep, depression, and antidepressant effects (Kinoshita et al. 2025).

He graduated from the Faculty of Medicine, The University of Tokyo in 2000, and obtained his Ph.D. in 2004 from the same university. He was appointed as a team leader in RIKEN in 2003. He became a full professor in Graduate School of Medicine, The University of Tokyo in 2013. He is also currently appointed as an affiliate professor in Institute of Life Science in Kurume University, an affiliate professor in Graduate School of Information Science and Technology in The University of Tokyo and Tokushima University. In 2016, he found the first sleep-promoting kinases, CaMKIIalpha and CaMKIIbeta and proposed the role of calcium and phosphorylation in sleep homeostasis. In 2018, he also found the first essential genes of REM sleep, muscarinic receptors M1 and M3. To accelerate these studies, he also invented whole-brain and whole-body clearing and imaging methods called CUBIC as well as the next-generation genetics (genetics without breeding) such as Triple-CRISPR and ES-mice methods for one-step production and analysis of KO and KI mice without crossing.