Research

Regulatory Mechanisms and (Patho) Physiological Functions of Mammalian Circadian Clocks

In response to daily environmental changes imposed by Earth’s rotation, almost all species, ranging from cyanobacteria to humans, have evolved physiological and behavioral rhythms called circadian rhythms.  Circadian rhythms are not passive responses to environmental changes; rather they are driven by an active clock system, capable of anticipating changes and coordinating tissue-specific function and generating systemic output responses.  The harmony between our intrinsic biological timing and the daily environmental oscillation is critical to physiological well-being; conversely, disrupted circadian rhythms have been shown to cause or increase the risk of various chronic diseases.  In our lab, we focus on delineating fundamental cellular mechanisms in circadian rhythms and also deciphering physiological and pathological roles of the clock.  Our long-term goal is to translate such fundamental mechanistic knowledge into new drug targets and therapeutic strategies for improved prevention and treatment of chronic diseases.

Currently, our labs are pursuing several projects, using an integrative approach combining mouse models with molecular and cellular mechanistic studies.  In one project, we investigate the role of miRNAs in circadian clock regulation using a second-generation circadian reporter mouse line Per2::LucSV (see Figure 1), with a particular focus on the mechanistic relationship between clock robustness and metabolic health.  In another project, we investigate the differential roles of two circadian E3 ligases (FBXL3 and FBXL21) in skeletal muscle structure and function.  Finally, we continue to pursue cloning of novel circadian clock mutants recently identified by a recessive mouse genetic screen.

Research Interests:

Circadian oscillator, miRNAs, F-box proteins, genomics, mouse models.