In 1988, Masashi Yanagisawa discovered endothelin that plays on the cardiovascular system. Ten years later, his team identified orexin as an orexigenic neuropeptide. Next year, he reported orexin-deficient mice showed narcoleptic phenotypes. Yanagisawa further succeeded in the identification of the endogenous ligands for GPR103 and GPR7, which are involved in the regulation of appetite, blood pressure and emotion.
Over 10 years of orexin research has convinced Yanagisawa that his team have to boldly take new approaches to gain fundamental insights on the mechanism of sleep/wake regulation. They carry out a large-scale forward genetic screen in a mutagenized cohort of mice, looking for new genes directly responsible for sleep/wake regulation. Their approaches include real-time visualization and manipulation of the activity of multiple neurons within the sleep/wake regulatory circuits in freely behaving mice. In a translational front, they aim at discovering and developing orexin receptor agonists in order to treat narcolepsy and other conditions associated with excessive sleepiness.