PI: Professor Gareth Sanger

This is a new area of research but good progress is being made and a network of collaborators is being established.

Nausea is common as a consequence of not just GI disease but occurs in all manner of physical illness, due to motion and as a result of therapy. There is evidence that the brain processing of nausea is different from that of vomiting. While the brain processing of all manner of human sensory experience has been studied using functional brain imaging techniques, there are no studies of the brain processing of the human nausea experience. Furthermore, there is considerable inter-individual variability in susceptibility to nausea, however, the biomarkers of nausea susceptibility are unknown. We are currently modelling nausea in humans by imaging and defining the brain areas which respond to the experience of nausea; additional blood and autonomic nervous system biomarkers are also being determined to identify subjects more susceptible to develop nausea. These biomarkers will be used to develop homogenous cohorts for drug trials.

Appetite and gastroparesis: disorders of appetite are common and obesity in particular is a major health hazard in western society. Gut hormones are instrumental in modulating satiety and hunger, however, their precise effects on human gut function are not known in health or diseases such as obesity. We are currently using human isolated gut preparations to study the effects of different hormones released from the gut during fasting and after eating, and the distributions of their receptors within the enteric nervous system, to determine how they affect gastro-colonic motility in vivo. Some of this work is already being used by industrial partners, to help guide dose selection for novel drugs aimed at treating disorders associated with delayed gastric emptying.

Strengths

1. Collaboration with acknowledged experts in the field
2. Access to human isolated stomach

References

1. Ng K, Chua Y, Gresty M, Marreddy U, Williams S, Barker G, Andrews P, Sanger G, Ban V, Wilson A, Chey S, Aziz Q. Identification of psychophysiological biomarkers of nausea using a novel visual induction method. Gut, 2010, 59 (Suppl 1), A30.
2. Broad J, Mukherjee S, Boundouki G, Dukes GE, Sanger GJ. Different abilities of motilin and the motilin receptor agonist GSK962040 to facilitate cholinergic and nitrergic activity in human isolated stomach. Neurogastroenterol Motil 2010.