Arisa HiranoArisa Hirano

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

Research Title

Neuroscience

From molecular to behavior; Aiming to understand mysterious biological phenomenon “Sleep” at various levels

01 Research Summary

We aim to understand why and how we sleep at night and wake up in the morning. In almost organisms living on the earth, many biological processes including sleep exhibit rhythms with a period of ~24 hours, which is called as circadian rhythms. Well-coordinated rhythms by internal time-keeping system, circadian clock, is essential for physical and mental health. We previously identified several gene variants in clock genes altering sleep/wake pattern in humans by forward genetics approach. It is thus well established that the circadian clock has a great impact on sleep/wake rhythms, while the neural pathway from the master clock in the brain (suprachiasmatic nucleus, SCN) to sleep/wake-regulating regions is still elusive. To understand the neural network controlling the circadian sleep behavior, we utilize gene-modified animals, macro injection and opto/chemo-genetics technics to evaluate the effect of manipulation of neurons in the SCN or clock-target regions on sleep/wake rhythms. In addition to the output pathway from the clock, we are also interested in oscillatory mechanism of the clock within the SCN neurons (intracellular oscillator) as well as mechanism of entrainment of the clock to environmental cycle such as light-dark cycle (input pathway), which are considered as three main factors of the circadian clock. We believe that understanding of the whole picture of the circadian clock is key to advance sleep study.


02 Major achievement

Hirano A, Hsu PK, Zhang L, Xing L, McMahon T, Yamazaki M, Ptáček LJ, Fu YH. “DEC2 modulates orexin expression and regulates sleep” Proceedings of the National Academy of Sciences of the United States of America. 2018, 115(13)3434-3439

Hirano A, Brass D, Fu YH, Ptáček LJ. “FAD Regulates CRYPTOCHROME Protein Stability and Circadian Clock in Mice” Cell Reports. 2017, 19(2)255-266

Hirano A, Fu YH, Ptáček LJ . “The intricate dance of post-translational modifications in the rhythm of life” Nature structural & molecular biology. 2016, 23(12)1053-1060

Hirano A, Yumimoto K, Tsunematsu R, Matsumoto M, Oyama M, Kozuka-Hata H, Nakagawa T, Lanjakornsiripan D, Nakayama KI, Fukada Y. “FBXL21 regulates oscillation of the circadian clock through ubiquitination and stabilization of cryptochromes” Cell. 2013, 152(5)1106-1118

03 Education/Academic background and major awards

Education/Academic background

Mar 2013 Ph.D. in Science (The University of Tokyo)
Apr 2013-Mar 2014 Project Assistant Professor, School of Science, The University of Tokyo
Apr 2014-Mar 2016 Overseas Research Fellow, Japan Society for the Promotion of Science
Apr 2014-Mar 2017 Postdoctoral Fellow, Department of Neurology, University of California, San Francisco
Apr 2017-Mar 2019 Assintant Investigator, International Institute for Integrative Sleep Medicine, University of Tsukuba
Apr 2019-Present Assistant Professor, Faculty of Medicine, University of Tsukuba/ Principal Investigator, International Institute for Integrative Sleep Medicine, University of Tsukuba

Awards

     
2012 Society for Research on Biological Rhythm Trainee Research Awards (The 13th Biennial Meeting Society for Research on Biological Rhythm Conference)
2013 President’s Award for Students (The University of Tokyo)
2013 The School of Science Encouragement Award (The University of Tokyo)
2014 Inoue Research Award for Young Scientists (Inoue Foundation of Science)
2018 Inoue Science Research Award (Inoue Foundation of Science)