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Qing-Jun Meng Lab

Research

Circadian clocks, ageing and age-related diseases: molecular links and therapeutic intervention

Age is the single biggest risk factor for a wide spectrum of diseases. The rapid population ageing needs better understanding of the various biological processes underlying age-related pathologies. Among these are circadian rhythms, the endogenous 24 hour cycles governing nearly all aspects of physiology and behaviour. In mammals (including humans), this rhythm is generated by the master clock (suprachiasmatic nucleus, SCN) in the brain, which entrains to the light/dark environment and co-ordinates the peripheral clocks in most major body organs and cells. Circadian clocks control ~10% of our transcriptome in a tissue-specific manner and disrupted circadian rhythms correlate with various pathologies. Mutations in core clock genes lead to metabolic syndrome, obesity, diabetes, premature ageing, and increased tumorigenesis.

My previous research focused on the molecular mechanisms of clock period regulation (Meng et al, 2008, Neuron) as well as the pharmacological resetting potentials of the circadian clock using compounds targeting various pathways (Meng et al 2008, J Cell Sci; Walton et al 2009, J Pharmacol Exp Ther; Meng et al 2010, PNAS; Li et al 2012, PLoS ONE). My current interest is the interface between ageing and circadian biology. Research in this laboratory aims to 1) Identify the mechanisms underlying age-related changes in circadian rhythms in both brain and peripheral organs. 2) Establish the functional significance of various tissue clocks in coordinating local physiology. 3) Explore the hypothesis of targeting body clocks in order to ameliorate disease development or progression. In the long term, outcomes from this work could aid therapeutic drug design against age-related ailments, such as osteoarthritis (Arthritis & Rheum 2013; Osteoarthritis & Carti 2015; J Clin Invest 2016; Nat Rev Rheum 2016), spinal disc degeneration (Annals Rheum Dis 2016), pulmonary fibrosis (Genes & Dev 2014), tendinopathies (Sci Rep 2014) and breast cancer (Nature Communications 2017).

 

Our research is generously funded by the following organizations:

Gene transcription round the clock.

Gene transcription round the clock.

Circadian expression profiles of three core clock genes (Bmal1, green; Rev-erba, blue; Per2, red) in fibroblasts revealed by real-time photon counting.

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Gene transcription round the clock.

Integrated approaches (from molecules, cells to behavior) to understand the clock changes with advanced age

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