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Understanding how Barrett’s oesophagus develops and identifying the cellular and molecular factors that induce, or are involved, in its onset

Barrett's oesophagus, could be viewed as a "homeotic shift" in which genes involved in cell fate determination developmentally have been reprogrammed in adulthood so that intestinal cells can be found in the squamous oesophagus. We hypothesise that refluxate could trigger these changes since gastro-duodeno-oesophageal reflux is the main known risk factor. In order to test this hypothesis we are employing several approaches:

  1. Immuno-fluorescence and confocal microscopy to study the cell organisation of the normal epithelium of the human oesophagus.
  2. Flow cytometry-based cell sorting and 3D culture to investigate which cells in human oesophagus are at the origin of the metaplasia. 
  3. Molecular biology techniques to identify the molecular factors that trigger Barrett’s development.
Barretts
3D reconstructions of a Barrett’s crypt stained for cytokeratin 8/18 (green) and DAPI (blue).
papilla detail
Normal oesophageal epithelium stained for cytokeratin 14 (red) and DAPI (Blue).

We have also developed a model system to study the development of Barrett's oesophagus in which retinoic acid is used to trigger changes reminiscent of Barrett’s metaplasia (Chang et al., Gut, 56(7):906-17, 2007). This has led us to consider the role of retinoic acid target genes as key regulators of this process. Use of this model system in conjunction with cell lines and human tissues provides us with the tools to study the cell biology of metaplasia (Barbera et al., Surg Oncol Clin N Am, 18(3):393-410, 2009).