The most common mutation of CFTR in North America is the DF508 deletion, which results in the absence of CFTR from the apical membrane. Presently, it is not clear how the lack of CFTR in the apical plasma membrane of IBE cells causes hepatobiliary disease. This laboratory has overcome this major problem by producing the only CF-IBE and matched normal IBE cell lines derived from humans. Altered secretion of HCO3- into the bile in CF could lead to significant changes in bile composition and flow which in turn can initiate injury to the liver. The goals of our studies are to identify the protein-partners of CFTR that are necessary for the regulation of anion exchanger activity and to and ultimately to investigate the mechanisms by which these interactions take place.
Inactivation is accomplished using chromophore-conjugated antibodies to a protein of interest.
This approach creates knockout phenotype in living cells in real time, thus preventing compensatory mechanisms that may override or mask the effects of protein inactivation. These studies will lead to a greater understanding of the function and physiology of the polycystin proteins.