Circadian function and intervention in the periphery and the brain
The circadian clock is our intrinsic biological timer orchestrating essential cellular and physiological processes. We initially identified clock-modulating small molecules (PNAS 2012) via high-throughput chemical screening and showed that these compounds can potently enhance peripheral and/or central circadian clocks. In subsequent studies, we showed that a naturally occurring flavonoid enriched in citrus peels, called Nobiletin, is a robust clock-enhancing molecule which confers potent clock-dependent protection against metabolic disorders and promote healthy aging in mice (Cell Metabolism 2016; Nature Communications 2019). Importantly, we identified the nuclear receptors RORs as the direct protein target of Nobiletin (see Figure). These studies laid an excellent foundation for our continuing investigation into circadian regulation of energy homeostasis throughout lifespan.
A growing interest in our lab is the circadian function in the brain and how it impacts central regulation of various behaviors. We have built a network of collaborators and infrastructure to particularly investigate circadian function and mechanism in neurodegeneration and related diseases using mouse models.
Circadian clocks, aging, metabolic disease, neurodegeneration, small molecule modulators, dietary intervention.