Ying-Hui Fu, PhD

Professor
Neurology
415-502-2948

Molecular Study of Human Sleep Behaviors

Our research focuses on hereditary neuro-related conditions, in particular circadian rhythm/sleep duration behavior traits. We collaborate closely with Dr. Louis Ptáček’s Laboratory. All of the work in our laboratory begins with human families segregating alleles for monogenic traits. Study of DNA from these families allows identification of the gene/mutation(s) responsible for the phenotype. In vitro studies of the wild-type and mutant proteins encoded by the gene then provide a window into relevant biological pathways and pathophysiology. In addition, we use model organisms such as mouse and fruit fly to probe physiology in vivo. The pursuit of the genetic and molecular basis of human behavior is extremely complex because of the wide variation in "normal" individuals. Furthermore, behaviors such as sleep are confounded by social and familio-cultural influences that frequently lead us to override our biological clock and stay up later or to wake up earlier than we otherwise would or shorten sleep duration. Various agents including caffeine and alcohol also confound one's ability to understand the inherent rhythms and sleep homeostasis dictating humans' activities. We have identified many and are still in the process of identifying more mutations that are involved in regulation of human rhythmicity and sleep duration. Our long-term goal is that as we find more mutations that are affecting human sleep behavioral patterns, we will characterize these mutations to assist us understand human circadian clock and sleep duration regulation.

Circadian and sleep schedule biology
Most organisms live in a continuously changing environment that varies in a rhythmic fashion related to the Earth’s rotation around its axis. This planetary movement produces a daily solar cycle with a periodicity of approximately 24-hr. Organisms have evolved an internal clock that responds to the daily solar cycle resulting in cycling of many physiological and behavioral responses with a period of about 24-hr. Disruption of circadian rhythmicity has been linked to many human disorders including insomnia, jet lag, stomach ailments, cardiovascular disease, depression, and cancer. We have collected many probands/families with autosomal dominant advanced sleep phase (FASP, extreme morning larks), and delayed sleep phase (FDSP, extreme night owls) traits and have identified several causative genes/mutations. Results from our studies on these mutations have yielded unexpected insights into mammalian circadian rhythm regulation.

Sleep duration variants in humans
Considering we spend one third of our lives in the state of sleep, our understanding of sleep regulation is very limited. Sleeping and waking are complex behaviors generated by elaborate mechanisms involving many areas of brain. Sleep and wakefulness and performance rhythms are diurnal rhythms that we consciously experience on a daily basis. Sleep disruption and duration has also been shown to have significant impact on human health, quality of life, and life expectancy. We have identified mutations that cause people to have shorter sleep duration than majority of population and yet they remain active and energetic during the day. Studies of these mutations will ultimately lead us to a better understanding of the regulatory mechanism for sleep duration.

Current Projects

  • Identify human sleep genes
  • Molecular studies of human sleep regulation
  • Molecular studies of human circadian rhythm regulatory mechanism
  • Characterize mouse models of de/dys-myelinating disease
  • Characterize miRNAs that are important for healthy myelin

Lab Members

William Hallows, PhD
Postdoctoral Fellow
william.hallows@ucsf.edu

Pei-ken Hsu, PhD
Postdoctoral Fellow
pei-ken.hsu@ucsf.edu

Arisa Hirano, PhD
Postdoctoral Fellow
arisa.hirano@ucsf.edu

Maya Yamazaki, PhD
Postdoctoral Fellow
maya.yamazaki@ucsf.edu

Guangsen Shi, PhD
Postdoctoral Fellow
guangsen.shi@ucsf.edu

Lijuan Xing, PhD
Postdoctoral Fellow
lijuan.xing@ucsf.edu

Philip Kurien, MD
Clinical Fellow
philip.kurien@ucsf.edu

Wonhee Woo, MD
Clinical Fellow
wonhee.woo@ucsf.edu

Ying Zhang
Laboratory Assistant
ying.zhang@ucsf.edu

Tom McMahon
Lab Manager
tom.mcmahon@ucsf.edu

Lab Website

Publications: