Professor David J Beech
- Position: Professor
- Areas of expertise: Ion channels in health and disease
- Email: D.J.Beech@leeds.ac.uk
- Phone: +44(0)113 343 4323
- Location: 7.27 LIGHT
I graduated in Pharmacology from the University of Manchester UK in 1985 before PhD study with Thomas Bolton at St George’s Hospital Medical School London and postdoctoral training with Bertil Hille at the University of Washington Seattle USA. In 1992 I established an independent research group at the University of Leeds UK, funded initially by a Wellcome Trust Postdoctoral Career Development Fellowship and then a full professorship since 2000. My research focusses on calcium-selective and calcium-permeable non-selective cationic channels of mammalian cells – their mechanisms, roles and potential as new therapeutic targets. I am particularly interested in the idea that the channels sense physical and chemical factors to regulate cardiovascular and metabolic health.
I have trained over 70 postgraduate and postdoctoral research scientists, published over 160 peer-reviewed articles, filed 2 patents, and delivered over 160 invited lectures worldwide. I was elected to Fellowship of the Academy of Medical Sciences in 2013 and became a Wellcome Trust Investigator in 2016 and British Heart Foundation Programme Grant Holder in 2018. Since 2016 I have been Director of the Leeds Institute of Cardiovascular and Metabolic Medicine, a research and student education organisation of over 200 staff in the School of Medicine at Leeds. I founded and continue to direct the British Heart Foundation 4-Year PhD Programme in Cardiovascular Disease and Diabetes and the Multidisciplinary Cardiovascular Research Centre, a pan-university / teaching-hospital structure for all cardiovascular research in the Leeds region.
- Institute Director
For over 30 years my field of interest has been ion channels in mammalian physiology and human disease. I initially focussed on the identification, function and regulation of potassium channels, discovering the KNDP channel and multiple types of voltage-gated potassium channel in vascular smooth muscle cells. As I built a research group I went on to discover ion channel mechanisms which enable or facilitate vascular smooth muscle cell switching to a migratory phenotype - an important mechanism in cardiovascular disease. The work led to a large family of non-voltage-gated non-selective cationic and calcium-selective channels encoded by multiple genes. We devised a strategy for generating inhibitor antibodies and used it to identify TRPC1, 4 and 5 proteins as mediators of calcium and sodium entry in human disease. We discovered that TRPC1 is upregulated by vascular injury.
We developed the idea that TRPC1-containing channels are sensors of lipid and redox factors and showed the principle of channel activation by extracellular redox protein; we led human tissue studies which suggested importance of the mechanism in arthritis – a principle later developed successfully by others. We generated the first insight into the molecular basis of calcium entry in adipocytes, showing that a TRPC1/TRPC5 channel negatively regulates serum adiponectin, an anti-inflammatory adipokine. With chemistry collaborators we discovered TRPC1/4/5 channels as the unexpected target of the African plant substance (-)-Englerin A and showed how (-)-Englerin A causes potent and selective cancer cell death by triggering sustained sodium entry. Ultimately we led the way in introducing a transformative set of pharmacological tools for TRPC1/4/5 channels which now include (-)-Englerin A and Tonantzitlolone (high potency selective agonists) and Pico145 (a picomolar selective antagonist with graded subtype selectivity). We discovered importance of Orai1 and Orai3 channels in calcium signalling by the growth factors VEGF and PDGF and through this work identified a novel calcium-sensitive Rab GTPase. We discovered the calcium- and sodium- permeable Piezo1 channel as a critical sensor of the mechanical force of shear stress caused by fluid flow and showed its essential role in integrating physiological force with vascular architecture - discovering and explaining the channel’s requirement in embryonic development. We provided critical evidence for endothelial Piezo1 channels as direct sensors of shear stress, showing distinct properties which enable compatibility with vascular biology and revealing how they control blood pressure and activate in response to increased whole body physical activity. We proposed the channels as exercise sensors and began to develop small-molecule Piezo1 modulators as potential enhancers of the health benefits of exercise.
- BSc Hons
- Fellow of the Academy of Medical Sciences
- Member of the Physiological Society
Director and teacher on the British Heart Foundation 4-Year PhD Programme in Cardiovascular Disease and Diabetes at Leeds
Research groups and institutes
- Leeds Institute of Cardiovascular and Metabolic Medicine
- Discovery and Translational Science