Gastrointestinal Pharmacology Group
The Brown lab has experience and expertise in dysfunction and pathologies affecting the entire length of the gastrointestinal tract. Dr Brown has worked in the field of gastroenterology for over 20 years, initially focusing on the control and signalling of gastric mucus and acid secretion before moving to the lower regions of the small and large intestine to explore dysfunctional motility and inflammation. Today, the group is examining the role of enteric glia in the aetiology and pathology of a broad range of conditions such as Barrett's oesophagus, inflammatory bowel disease and colonic polyps. Collaborations between Queen Alexandra Hospital and this lab are exploring links between bacterial colonisation and enteric glial cell function. In addition, we are also looking at novel methods of improving diagnostic precision in both upper and lower gastrointestinal endoscopy.
Our current laboratory research
Enteric glia in gastrointestinal physiology and pathology
The enteric nervous system (ENS) is often considered as the third division of the autonomic system. It is a complex structure that organises and controls both secretory and motility function. Glia are found throughout the ENS and outnumber neurons by approximately 4:1. Enteric glia are now believed to offer not just structural but also biochemical support to neurons and may also function as immune modulators. Thus, glia are likely to play important roles in inflammatory conditions such as ulcerative colitis and Crohn’s disease as well as functional disorders such as irritable bowel syndrome and polyp formation.
In collaboration with Prof Arthur Butt (enteric glia) and Prof. Pradeep Bhandari (consultant endoscopist , QA Hospital), the overarching goal is to identify the precise role of glia in a broad range of intestinal pathologies. Collaborations also exist with Prof. Jan Shute (inflammation), Dr Jerome Swinny (GABA, glia and dysmotility) and Dr Vitaly Zinkevich (bacteria, glia and inflammation) and Prof. Darek Gorecki (muscular dystrophy and gastrointestinal pathologies).
Imaging techniques to enhance diagnostic precision during gastrointestinal endoscopy
Endoscopy has advanced considerably in the past 20 years with the number of procedures increasing year on year for an increasingly widening range of indications. Advanced endoscopic imaging techniques such as high definition endoscopy, magnification endoscopy, electronic chromoendoscopy, dye sprays and endomicroscopy have been developed to enhance lesion detection and characterisation during endoscopy. Many of these are being used in daily practice. However, despite promising initial data, the evidence base for their reliability and effectiveness is not yet robust and further work needs to be undertaken in this area.
Under the direction of Prof. Pradeep Bhandari (QA Hospital), the group is exploring methods to improve training and early detection of neoplasia such as dysplastic changes within Barrett's oesophagus and the detection of diminutive polyps within the colon.
Expression and function of GABAA receptor subtypes in the enteric nervous system of mammalian colon
Irritable bowel syndrome (IBS) is a debilitating gastro-intestinal (GI) disorder characterised by abdominal pain and discomfort and accompanied by altered bowel habits. IBS is a multifactorial disorder involving impairment in the brain-gut axis, gastrointestinal motor and sensory dysfunction, enteric and central nervous system irregularities and neuro-immune dysregulation, resulting in a lack of clear therapeutic targets. GABAA receptors (GABAARs) are entirely unexplored as therapeutic targets for the treatment of IBS despite the expression of these neurotransmitter receptors in the enteric nervous system (ENS). In collaboration and under the direction of Dr Jerome Swinny, the group is exploring the role of GABAAR's in the mammalian intestine with the intention of identifying novel therapeutic targets for the treatment of IBS.