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Treatment of Cystic Fibrosis with Heat Stable Toxin Isolated from Escherichia coli
Mr. Andrew Chapp
Doctoral student, Department of Chemistry, Michigan Technological University
|11/17/2011 - 10:00 am - Room 404, Administration Building|
Cystic Fibrosis (CF) patients suffer from a number of lung abnormalities including: a dysfunctional CF transmembrane conductance regulator (CFTR) protein leading to reduced chloride ion secretion, an over-activated epithelial sodium channel (ENaC) leading to hyperabsorption of sodium ions and hyperacidification of the trans-Golgi network (TGN), impaired mucosal clearance and mucous hydration that eventually leads to lung infections and subsequent lung failure in the majority of CF patients. Heat stable toxin (HST) from Escherichia coli and HST analogues provide a solution to a majority of the underlying CF lung pathologies by simple activation of the guanylyl cyclase receptor (GCR) and subsequent upregulation of cyclic guanosine monophosphate (cGMP). cGMP has been shown to activate alternative chloride channels, fast movement water channels and inhibit sodium absorption through ENaC. Patch clamp testing of CF cell lines treated with HST and HST analogues that conserve the disulfide loop structure crucial to GCR activation will be used to determine the efficacy of ENaC inhibition and whether GCR targeting for CF is a viable treatment option.