Home| Professor of Neuropharmacology |
Contact details:
| Tel: | +44 20 7882 2639 |
| Fax: | +44 20 7375 2103 |
| Email: | g.sanger@qmul.ac.uk |
| Address: | Centre for Digestive Diseases, |
Biography
- BSc (physiology, University of Newcastle), PhD (physiology, University of Manchester), DSc (University of Manchester). Fellow of the British Pharmacology Society.
- Post-doctoral fellow with Professor Alan Bennett (Kings College Hospital Medical School), examining the functions of newly-discovered prostanoids on human isolated gastrointestinal muscle and myometrium.
- Drug Discovery and Gastrointestinal Research at GlaxoSmithKline (after three mergers). Experience in all phases of drug discovery. Led or played leading roles in many different teams, placing 7 novel compounds into development, including granisetron (now an anti-emetic drug) and another still in development. Research achievements included:
- The proposal that a novel receptor mediated the ability of 5-HT to increase gastrointestinal motility, later named by others as the 5-HT4 receptor.
- Identification of the role of the 5-HT3 receptor in the mechanisms of emesis, which led to the development of new drugs and a major change in the treatment of cancer.
- Jointly awarded the 1998 Discoverer’s Award by the Pharmaceutical Research and Manufacturers of America (PhRMA).
- Exploration of several different gastrointestinal research areas, including the actions mediated by NK3, ghrelin and motilin receptors.
- Over 100 peer-reviewed papers and over 50 review articles and book chapters.
- Twice served on the Editorial Board for the British Journal of Pharmacology.
- Consultant on gastrointestinal drug discovery and development
Research Activity
Functional human tissue assays. This is a new laboratory, focused on the use of fresh, ethically-obtained human gastrointestinal tissues to predict activity in vivo. Human tissues include esophagus, stomach, ileum and colon. Functional human tissue assays include those which study neuromuscular pharmacology (after electrically stimulating cholinergic, nitrergic and tachykinergic functions to cause contraction or relaxation), human mucosal permeability and mucosal secretion (Ussing chambers) and in the near future, human peristalsis (by evoking reflex activity in human isolated colon). Assays are complimented by human gastrointestinal immunohistochemistry, to confirm the cell types of interest. In the functional human tissue assays, actions of novel substances are benchmarked against those of clinically-relevant drugs, enabling us to predict physiological, therapeutic and adverse effects of novel substances in the clinic, as well as comment on the potency and doses of new drugs. Our focus on human tissue pharmacology means we are involved in basic research with immediate clinical relevance, as well as providing contract services to industry, where our expertise plays a vital role in innovative drug discovery.
Current research interests. These include the effects of the different hormones, released from the gut during fasting or after eating, on human gastrointestinal function. These are studied using human isolated stomach and colon, and the effects related to changes in gastrointestinal motility, BMI, appetite and nausea. We have characterized the pharmacology of neuronally-mediated responses evoked by electrical field stimulation and demonstrated (for the first time) an ability of motilin to facilitate both cholinergic and nitrergic activity in human isolated gastric fundus and antrum. These experiments provide a mechanism for the prokinetic activity of this peptide, demonstrate regional differences in magnitude of activity and because differences in durations of response were observed between motilin and a small molecule non-peptide ligand, suggest differences ways in how different molecules interact with the motilin receptor. Similar experiments with human isolated colon have characterized neuronally-mediated responses in human isolated colon and demonstrated facilitation of cholinergic and nitrergic activity with the 5-HT4 receptor agonist prucalopride. We are currently studying the effects of a number of different ways in which human colonic motility and secretion can be modulated.
Key Publications
• Sanger GJ, Westaway SM, Barnes AA, MacPherson DT, Muir AI, Jarvie EM, Bolton V, Cellek S, Näslund E, Hellström PM, Borman RA, Unsworth WP, Matthews KL, Lee K (2009). GSK962040A: a small molecule, selective motilin receptor agonist, effective as a stimulant of human and rabbit gastrointestinal motility. Neurogastroenterol Motil., 21, 657-666.
• Holbrook JD, Gill CH, Zebda N, Spencer JP, Leyland R, Rance KH, Trinh H, Balmer G, Kelly FM, Yusaf SP, Courtney N, Luck J, Rhodes A, Modha S, Moore SE, Sanger GJ, Gunthorpe M (2009). Characterisation of 5-HT3c, 5-HT3d and 5-HT3e receptor subunits: evolution, distribution and function. J Neurochem., 108, 384-396.
• Bassil AK, Borman RA, Jarvie EM, McArthur-Wilson RJ, Thangiah R, Sung EZ, Lee K, Sanger GJ (2008) Activation of prostaglandin EP receptors by lubiprostone in rat and human stomach and colon. Br J Pharmacol., 154, 126-135
• Dass NB, Bassil AK, North-Laidler VJ, Morrow R, Aziz E, Tuladhar BR, Sanger GJ (2007). Neuromedin U can exert colon-specific, enteric nerve-mediated prokinetic activity, via a pathway involving NMU-1 receptor activation. Br J Pharmacol., 150, 502-508.
• Bassil AK, Häglund Y, Brown J, Rudholm T, Hellström PM, Näslund E, Lee K, Sanger GJ (2007). Little or no ability of obestatin to interact with ghrelin or modify motility in the rat gastrointestinal tract. Br J Pharmacol., 150, 58-64.
• Dass NB, John AK, Bassil AK, Crumbley CW, Shehee WR, Maurio FP, Moore GBT, Taylor CM, Sanger GJ (2007). The relationship between the effects of short-chain fatty acids on intestinal motility in vitro and GPR43 receptor activation. Neurogastro Motil., 19, 66-74.
• Bassil A, Dass NM, Sanger GJ (2006).The gastric prokinetic-like activity of ghrelin in rat isolated stomach is mediated via cholinergic and tachykininergic motor neurones. Eur J Pharmacol., 544, 146-152.
• Rudd JA, Ngan, MP, Wai MK, King AG, Witherington J, Andrews PLR, Sanger GJ (2006). Anti-emetic activity of ghrelin in ferrets exposed to the cytotoxic anti-cancer agent cisplatin. Neurosci Lett., 392, 79-83.
• Dass NB, Hill J, Muir A, Testa T, Wise A, Sanger GJ (2003) The rabbit motilin receptor: molecular characterisation and pharmacology. Br J Pharmacol., 140, 948 – 954.
• Dass NB, Monunyara M, Bassil AK, Hervieu GJ, Osbourne S, Corcoran S, Morgan M, Sanger GJ (2003). Growth hormone secretagogue receptors in the rat and human gastrointestinal tract and the effects of ghrelin. Neuroscience, 120, 443-453
