L Ashley Blackshaw
Professor of Enteric Neuroscience
L Ashley Blackshaw, PhD, joined the Wingate in October 2011, taking up the position of Professor of Enteric Neuroscience. This was made possible by a Wellcome Trust University Award on "The anatomical, physiological and molecular basis of chronic visceral pain in humans".
His undergraduate education was at Sheffield University, where he remained for his PhD (1988) and postdoc with David Grundy. His early work identified contributions of different sensory inputs towards vagal reflexes, after which he established the activation of vagal sensory fibres by enteroendocine mediators. He moved to the Royal Adelaide Hospital and University of Adelaide in 1991 to work with John Dent on neural mechanisms of gastro-oesophageal reflux. He revealed novel peripheral neural targets to reduce triggering of reflux episodes. Over 20 years he built a major group in Adelaide, with which he retains collaborative links.
Professor Blackshaw's research now focuses on gastrointestinal sensory mechanisms in a range of disease indications including pain, obesity and reflux disease. His work has identified new classes of sensory neurones and demonstrated important therapeutic roles for receptors on these neurones. He has revealed the role of specific genes in mechanosensory function and pain in the GI tract. His main work also covers the role of gut endocrine cells in nutrient sensing and how this may be responsible for obesity.
Visceral sensory function
Professor Blackshaw is involved with three projects within the Neurogastroenterology Group:
Characterization of human visceral afferents
Based on work in animal models, we know there are several distinct types of sensory fibres innervating the gut. The aim of this project is to determine the types of fibres in human gut. This is critical information if we are to know how humans perceive pain and other sensations, and for us to design new drugs to alleviate pain. The research is carried out by electrophysiological recordings of nerve branches as they exit the bowel in surgical resections which are otherwise destroyed.
Nutrient sensing in the human intestine
Obesity is a huge modern problem, chiefly caused by humans' ability to ignore sensations of fullness after meals. A major site of generation of these sensations is in the intestinal epithelium, where specialized entero-endocrine cells respond to nutrients by releasing hormones that affect the way we feel and how we eat. This project aims to understand how these cells perform this function and how it is changed in obesity. It involves the mapping of activation markers in entero-endocrine cells in response to specific macronutrients, and subsequent phenotyping of their function.
Fundamentals of oesophageal pain
When we have acid reflux from the stomach it often hurts, but in some individuals this has a major impact on their quality of life. This project investigates the way acid evokes pain, and how its action can be attenuated in hypersensitive patients without losing important signals that warn us of cell damage. It involves use of activation markers in oesophageal sensory pathways and pharmacological studies aimed to reduce activation.
Kentish S, Li H, Philp LK, O'Donnell TA, Isaacs NJ, Young RL, Wittert GA, Blackshaw LA, Page AJ. Diet induced adaptation of vagal afferent function. J Physiol. 2011 Nov 7. PMID: 22063628
Blackshaw LA, Brierley SM, Hughes PA. TRP channels: new targets for visceral pain. Gut 2010; 59: 126-35.
Page AJ, O’Donnell TA, Cooper NJ, Young RL, Blackshaw LA. Nitric oxide as an endogenous peripheral modulator of sensory neuronal function. J Neurosci 2009; 29: 7246-55.
Young RL, Page AJ, Cooper NJ, Frisby CL Blackshaw LA. Sensory and motor innervation of the crural diaphragm by the vagus nerves. Gastroenterology 2010; 138: 1091-101.
Hughes PA, Brierley SM, Martin CM, Brookes SJH, Linden DR and Blackshaw LA. Post-inflammatory colonic afferent sensitization: different subtypes, different pathways, and different time-courses. Gut 2009; 58: 1333-41.