• Lung Cancer
• Wnt Signalling Pathway
• Bronchioalveolar Carcinoma
• Cancer Stem Cells
• Esophageal Cancer
• Mesothelioma
• Expression Profiling
• Lung Cancer System Genetics
• KRas Pathway
• Other Cancers
• Diagnostics Development

Esophageal adenocarcinoma (EAC) is now the fastest growing malignancy in the Western world. It is extraordinarily difficult to treat and has an overall five-year survival of less than 15%. In recent years, there has been an alarming increase in the incidence of esophageal cancer, this against a backdrop where death rates from other cancers are dropping across the United States.

EAC is thought to result from inflammation caused by chronic gastroesophageal reflux disease (GERD). EAC is preceded by the replacement of the normal squamous epithelium in the distal esophagus with a metaplastic columnar epithelium, otherwise known as Barrett's esophagus (BE-a pre-malignant condition that arises as a complication of chronic GERD). In BE carcinogenesis, the early metaplastic epithelium develops sequentially into low-grade dysplasia, high-grade dysplasia, early adenocarcinoma, and finally invasive cancer. However, the pathogenesis of EAC is poorly understood, and the molecular mechanism by which esophageal epithelial cells undergo neoplastic transformation is largely unknown. That being said, the progression of EAC provides an exquisite multi-step model for the investigation of the intermediate events in carcinogenesis.

We have already shown that the Wnt signaling pathway is activated during BE carcinogenesis. Other studies have demonstrated that Hh is similarly activated in BE and esophageal carcinogenesis. Notably, both these Wnt and Hh activations occur early in the neoplastic progression of BE. Because BE is an inflammatory condition resulting from chronic GERD, the group hypothesizes that infiltrating immune cells may activate the Wnt and/or Hh signaling cascades in pre-malignant epithelial cells, potentiating neoplastic transformation. The group proposes to elucidate the role played by the Wnt and Hh pathways in BE carcinogenesis, to discover new molecular markers of increased EAC risk in BE patients, and to investigate whether immune cells, resulting from chronic inflammation, may be implicated in tumorigenesis through regulation of the Wnt and Hh pathways.