Research

The molecular clock is a transcription-translational feedback loop driven by the core circadian factors. These core clock proteins also controls rhythmic expression of a large array of circadian output genes, including the key factors involved in metabolic pathways. My lab uses both in vitro cell culture and in vivo mouse model to study how the cyclic transcription events during the 24h period are achieved, by identifying the circadian-responsive cis-elements, temporal recruitment of circadian proteins and transcriptional cofactors and epigenetic markers.

The functional molecular clock is found not only in the central pace maker, SCN, but also various peripheral tissues. What is unknown is how these peripheral clock tissues contribute to the circadian control of metabolic processes. My lab is focusing on the liver clock because of its central role in glucose, lipid and cholesterol metabolism. My lab has developed a high-efficient method to manipulate the expression of core clock genes in liver using the adenoviral-based gene transduction. We will study the impact on both glucose and lipid metabolism and the related molecular pathways in these liver-specific circadian mouse models.

The majority of the core clock proteins have been shown to be targeted by the ubiquitination-proteasome system, raising a possibility that ubiquitination-dependent regulation is an essential component of molecular clock network. My lab is interested in identifying proteins or enzymes that are required for ubiquitination of core clock proteins (, mapping the ubiquitination sites within individual clock protein and characterizing the circadian function of non-ubiquitination clock protein mutants. The future plan is to create a knock-in mouse model with a targeted mutation in order to address the causative role of impaired circadian clock in the onset and progression of metabolic diseases.

Potential rotation projects:

Investigate regulation of molecular clock by chronic inflammation in obesity and diabetes.

Characterize the function of clock protein CRY1 ubiquitination.

Identify novel DUB enzymes for clock protein CRY2.