Professor of Endocrinology
David trained in general internal medicine in North West England, and obtained a PhD from the University of Manchester. He was a research fellow at UCLA for two years, working on neuroendocrine-immune interaction, before returning to the UK, and obtaining a GSK fellowship to work on glucocorticoid action, and sensitivity in inflammatory disease. He was promoted to Professor of Medicine at the University of Manchester in 2005, and went on to study nuclear receptor and circadian biology in inflammation, and energy metabolism. This work attracted Wellcome Investigator and MRC programme grant support.
David is a passionate advocate of research training, serving on the MRC clinical fellowship panel for seven years, three as deputy chair.
Circadian mechanisms regulate most mammalian physiology, with particular importance in the regulation of innate immunity, through the macrophage in particular, and energy metabolism, regulating liver, adipose and muscle. These circuits are also regulated by a number of nuclear receptors, which show a striking interdependency on the circadian machinery; some having ligand availability regulated by the clock, others varying in expression level through the day. We have employed a range of approaches to address the physiological importance of the circadian:nuclear receptor system, ranging from population genetics, experimental medicine studies, CRISPR engineered mice, and cell biology. These approaches have discovered how the important dimension of time regulates metabolism, and coordinates diverse tissues to deliver optimal organismal performance. Importantly, we are identifying how external stressors can decouple these systems, with deleterious effects.
Hypoxia regulates GR function through multiple mechanisms involving microRNAs 103 and 107.
Yang N. et al, (2020), Mol Cell Endocrinol, 518
Circadian asthma airway responses are gated by REV-ERBα.
Durrington HJ. et al, (2020), Eur Respir J
Glucocorticoids rapidly inhibit cell migration through a novel, non-transcriptional HDAC6 pathway.
Kershaw S. et al, (2020), J Cell Sci
Night Shift Work Increases the Risk of Asthma
Maidstone R. et al, (2020)
Understanding the Pathophysiological Mechanisms of Cardiometabolic Complications in Obstructive Sleep Apnoea - Towards Personalised Treatment Approaches.
Ryan S. et al, (2020), Eur Respir J