Barrett's Metaplasia

Barrett’s metaplasia is a condition in which the lining of the lower end of the oesophagus (gullet) changes from one cell type (a multi-layered tissue known as stratified squamous epithelium) into another (single cell layer which has features typical of intestinal type epithelium). The disease is associated with the reflux of acid and bile from the stomach and duodenum into the oesophagus, but the exact mechanism by which this initial change in the oesophageal lining occurs is poorly understood at present. Barrett’s metaplasia predisposes to oesophageal cancer, whose incidence has risen rapidly in the last three decades and carries a poor prognosis.

In order to achieve a better understanding of what drives the changes in Barrett’s metaplasia we are studying certain genes which are important in intestinal development. Recent evidence suggests that cdx2, a gene normally important in the development of the intestine but not expressed in the oesophagus, may be involved in Barrett’s metaplasia. We are currently researching methods to determine whether expression of cdx2 in the oesophagus can prompt a transdifferentiation from stratified squamous epithelium into intestinal type epithelium, which will increase our understanding of the disease process and may ultimately allow gene therapy to reverse the metaplastic process.

At present these techniques are experimental and cannot be applied to humans.

Normal intestine expresses cdx2 (stained green)