Qing-Jun Meng, MSc PhD
Circadian clocks, ageing and age-related diseases: molecular links and therapeutic potential
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 (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. In particular, I aim to address the molecular mechanisms underpinning the tissue-specific changes in circadian rhythms with advanced age. In the long term, outcomes from this work could aid therapeutic drug design against age-related ailments, such as osteoarthritis (Gossan et al 2013, Arthritis & Rheumatism), pulmonary fibrosis (Pekovic-Vaughan et al 2014, Genes & Dev), and breast cancer.
Tel: +44 (0) 161 306 8912
E-mail: Qing-jun Meng
Website: Lab website
Recent key publications
Gossan, N., Zeef, L., Hensman, J., Hughes, A., Bateman, J.F., Rowley, L., Little, C.B., Piggins, H.D., Rattray, M., Boot-Handford, R.P. and Meng, Q.J. (2013). The circadian clock in chondrocytes regulates genes controlling key aspects of cartilage homeostasis. Arthritis Rheum. 65, 2334-45. PubMed
Gossan, N., Zhang, F., Guo, B., Jin, D., Yoshitane, H., Yao, A., Glossop, N., Zhang, Y., Fukada, Y. and Meng, Q.J. (2014). The E3 ubiquitin ligase UBE3A is an integral component of the mammalian and Drosophila circadian clock. Nucleic Acids Res. in press.
Pekovic-Vaughan, V., Gibbs, J., Yoshitane, H., Yang, N., Pathiranage, D., Guo, B., Sagami, A., Taguchi, K., Bechtold, D., Loudon, A., Yamamoto, M., Chan, J., van der Horst, G.T., Fukada, Y. and Meng, Q.J. (2014). The circadian clock regulates rhythmic activation of the NRF2/glutathione-mediated antioxidant defense pathway to modulate pulmonary fibrosis. Genes Dev. 28, 548-60. PubMed