Currently, resitance to apoptosis and implication of NF-?UB/STAT3 activation are two major research areas are being investigated extensively in Dr’s Hormi-Carver’s laboratory. Understanding the molecular mechanism of bile reflux in the neoplastic progression of Barrett!|s esophagus may lead to a change in our current management strategies for patients with this disease. Furthermore, identifying the molecular events triggered by bile reflux may allow for the development of specific chemopreventive agents to prevent progression to malignancy. Dr. Hormi-Carver’s preliminary data demonstrate that compared to normal esophageal squamous cells, metaplastic Barrett!|s cells have minimal induction of p53 protein and apoptosis rates following exposure to UV-B suggesting that altered p53 expression, in response to DNA damage, contributes to the difference in apoptosis rates between esophageal squamous and metaplastic Barrett!|s mucosa. Metaplastic Barrett!|s epithelial cells were also found to have increased levels of, a very known protein implicated in conferring resistance to apoptosis, NF-?UB, suggesting that Barrett!|s metaplastic cells are resistant to the apoptosis normally induced by DNA damage, a feature that may underlie their malignant predisposition. Dr. Hormi-Carver’s hypothesize that alterations in p53 expression and NF-?UB/STAT3 activation following bile acid exposure contribute to the apoptotic resistant phenotype of metaplastic Barrett!|s epithelial cells. To test this hypothese, she propose to investigate the effects of deoxycholic acid, a conjugated bile, on p53, anti-apoptotic proteins expression and on NF-?UB/STAT3 activation and also on the rates of apoptosis in normal esophageal squamous and metaplastic Barrett!|s epithelial cells in vitro.
