Along the development of the projects FFC#6/2013 and FFC#29/2015 researchers set up a method to assay CFTR activity in leukocytes by using an iodine-sensitive YFP recombinant protein (HS-YFP) able to detect differential iodine transport between WT and CF leukocyte and to monitor the effect of ivacaftor on CFTR activity of CF patients carrying class III gating mutations. However, this procedure cannot reveal any information about biochemical changes and the cellular mechanisms related to the restored CFTR activity. With this project researchers aim to identify proteomic changes as a direct consequence of a restored CFTR activity in CF leukocytes, by combining together HS-YFP fluorescence assay of CFTR activity with proteomic analysis on CF leukocytes before and after ex vivo treatment with VX-77o. They plan to assay CFTR activity on leukocytes of 15-20 CF patients carrying class III gating mutations and non-gating mutations with residual functioning CFTR, before and after ex vivo treatment with VX-770, in order to correlate the CFTR functional recovery with protein changes identified by a subsequent proteomic analysis. The perspective is to identify new markers reflecting the modifications in leukocyte (monocytes) protein pattern as a direct consequence of a restored ex vivo CFTR activity after VX-770 cells treatment. This cellular model has the advantage to be readily available and could be used for the evaluation/prediction of the efficacy of new therapies targeting the defect of chloride transport in cystic fibrosis.