Masashi Yanagisawa

Affiliation:International Institute for Integrative Sleep Medicine, University of Tsukuba

Research Title


Solving the mystery of sleep
~Developing new intervention methods for healthy slumber~ 

01 Research Summary

Sleep is a quite familiar phenomenon. However, underlying mechanisms of sleep is unknown and even simple questions, why we sleep and what sleepiness is, are unanswered. Thus, sleep is one of the greatest mysteries in today’s neuroscience. Our discovery of orexin unlocked the door to the sleep studies, but sleep/wake regulation still remains a challenge for scientists. In order to crack open the black box, Yanagisawa/Funato Lab is engaged in basic research using forward genetic analysis, in vivo calcium imaging, patch-clamp electrophysiology in brain slices with simultaneous multicellular recording and imaging, etc., in addition to drug discovery research targeting the orexin receptor. We have identified three or more causative gene mutations that play important roles in sleep-wake regulation to date, through advances of our forward genetics research. People in our lab are vigorously conducting experiments everyday with the aim of solving the mystery of sleep, and contributing to the reduction of sleep disorders and associated diseases.

Yanagisawa & Funato Laboratory

Yanagisawa & Funato Laboratory

02 Major achievements

Funato H., Miyoshi C., Fujiyama T., Kanda T., Sato M., Wang Z., Ma J., Nakane S., Tomita J., Ikkyu A., Kakizaki M., Hotta N., Kanno S., Komiya H., Asano F., Honda T., Kim J.S., Harano K., Muramoto H., Yonezawa T., Mizuno S., Miyazaki S., Connor L., Kumar V., Miura I., Suzuki T., Watanabe A., Abe M., Sugiyama F., Takahashi S., Sakimura K., Hayashi Y., Liu Q., Kume K., Wakana S., Takahashi J.S., Yanagisawa M. Forward genetic analysis of sleep in randomly mutagenized mice. Nature 539: 378-383, 2016

Ogawa, Y., Irukayama-Tomobe, Y., Murakoshi, N., Kiyama, M., Ishikawa, Y., Hosokawa, N., Tominaga, H., Uchida, S., Kimura, S., Kanuka, M., Morita, M., Hamada, M., Takahashi, S., Hayashi, Y., Yanagisawa, M. Peripherally administered orexin improves survival of mice with endotoxin shock. eLife DOI: 10.7554/eLife.21055, 2016

Irukayama-Tomobe, Y., Ogawa, Y., Tominaga, H., Ishikawa, Y., Hosokawa, N., Ambai, S., Kawabe, Y., Uchida, S., Nakajima, R., Saitoh, T., Kanda, T., Vogt, K., Sakurai, T., Nagase, H., Yanagisawa, M. A non-peptide orexin type-2 receptor agonist ameliorates narcolepsy-cataplexy symptoms in mouse models. Proc. Natl. Acad. Sci. USA DOI: 10.1073/pnas.1700499114, 2017

03 Education/Academic background and major awards

In 1988, as a graduate student at University of Tsukuba, Yanagisawa discovered endothelin, a potent vasoconstrictor peptide from vascular endothelial cells, which sparked an intense research activity in the field. After moving to University of Texas Southwestern Medical Center at Dallas in 1991 as a young principal investigator, he identified the endothelin-converting enzyme, a metalloprotease that generate the active, mature endothelin peptides. In 1996, he initiated a systematic search for endogenous ligands of “orphan” G protein-coupled receptors, which resulted in his 1998 discovery of orexin, a hypothalamic neuropeptide. He then discovered in 1999 that orexin deficiency causes the sleep disorder narcolepsy. This opened up a new avenue in sleep research, and led to a better understanding of sleep/wake switching mechanisms in the brain. Now, he pulls all his energy to solve the fundamental mechanism for sleep homeostasis which is still remains a mystery as a professor and a director in IIIS


Why did you become a scientist?

I want to cure the patients the day after tomorrow than treat the patients now

My mother told me that I wanted to be a scientist ever since I was in first grade of elementary school. I was a peculiar child, in the sense that I would visit the nearest creek and observed how the water would swirl and flow down for about an hour. I was curious of my surroundings but, now that I think back on it, I was doing something a little dangerous for my age. Maybe it’s just a proof of how much I love Natural Science. Later, I went to medical school where I made the biggest decision of my life on Graduation day; “I want to cure the patients tomorrow than treat the patients now”. With this in mind, I decided to leave clinical practice to focus on the fundamental research as a researcher.

What are the characteristics of your lab?

To be free.

I believe that scientists should be “independent and free” in their research. This is why I do my best to provide a suitable environment for scientists to pursue the research that they truly are passionate about, not forced on to them. I also try to adopt the ‘Open advocacy policy’ that a lot of professors in the U.S. practice. Basically, anyone is welcome to discuss what one has in mind when the door of my office is open. I also gather students and have a journal club/dinner to discuss original research articles. The topic of discussion in these gatherings really varies from researches, everyday life, and anything else. By providing these type of spaces, I try my best for the students to not only enjoy their work, but for them to be free and independent.

What are you most interested in lately

Listening to classical music, playing the flute

When I was an elementary schoolboy, I used to play the piano. I never really worked hard on it so I never really improved much. My teacher, however, was fantastic. At the time, she taught me about harmony and the basics in a way even a schoolboy like myself would understand. I found out later that she was the mother of a famous pianist, Akiko Ebi. When I entered Junior High, I met a teacher who was really into classical music, even though he didn’t graduate from music school or could properly play any musical instruments. He brought his own stereo and played classical music, which we listen while following the scores in hand. Unlike other classes, there wasn’t a care about who was good or bad at something but just the process of learning music theoretically. It was so much fun and I love classical music ever since then. I also play the flute.