In vivo tracking of bioluminescent markers of circadian rhythms in behaving animals

We are developing a new technique to measure gene expression in behaving animals continuously in real-time. Based on the honors thesis research of Wanqi Wang (’17) and currently assisted by Reja Javed (’18), we are testing equipment designed by David Ferster (Actimetrics).  We can measure circadian rhythms of PER2::LUC indefinitely when luciferin is given in the drinking water, a technique that we can apply to mice that are behaviorally arrhythmic.  We can also measure rhythms using a new synthetic luciferin developed by Stephen MIller (UMassMed) delivered by an osmotic mini-pump.  We plan to develop this technique for dissemination, and to begin experiments targeting specific tissues, as animals become available. We hope to be able to answer questions in our future studies such as…..Does a high amplitude rhythm protect us from negative health impacts on metabolism or from cancer?  Can exercise and diet manipulations increase circadian rhythm amplitude of specific tissues?  

Effects of Frequent Jet Lag or Rotating Shift Work on Health

What is the impact of disruption of circadian rhythms on health? Epidemiological studies suggest a link between occupations that involve shift work or frequent jet lag and increased incidence of cancer, cardiovascular disease, and other negative health consequences. Patients with metastatic disease show better outcome if their circadian rhythms are more robust. How might disruption of circadian rhythms alter the multitude of pathways that lead to cancer, cardiovascular disease or poor health? We are using behavioral and bioluminescent measures to study disruption of circadian rhythms and the impact on physiology.  We currently collaborate in a research project looking at effects of sleep loss and circadian rhythm disruption on metabolism, funded by NIH NIA.

Developing an animal model for the study of fatigue

Fatigue is estimated to cost US employers more than $100 billion a year. Our prior research funded by the NIH National Cancer Institute tested if cytokines act on the circadian clock to cause cancer-related fatigue. This led to our research funded by the National Institute of Nursing Research attempting to develop an animal model of fatigue based on inflammation. We are studying how the brain changes in the state of fatigue with the goal of using this understanding to test and develop new treatments.

Studies of circadian clock coupling among hepatocytes 

We have just finished studying circadian rhythms in the liver using primary hepatocyte cultures. The goal of this research was to determine if and how cells in the liver show circadian clock coupling. This work is funded by the National Science Foundation. We discovered that liver cells show weak local coupling.