Background and Rationale. Cystic Fibrosis (CF) is a life-shortening genetic disorder, caused by mutations of Cystic Fibrosis Transmembrane-conductance Regulator (CFTR) [1]. In particular, the most common F508delCFTR mutant is unable to traffic to and reside at the plasma membrane (PM) [2]. Currently, no highly effective CFTR-repairing therapies are available for F508del-CFTR. For this reason our novel approach aims at targeting the derailed CF intracellular environment, and not directly the mutant CFTR, through a combination of drugs (e.g. cysteamine and epigallocatechin-gallate, EGCG) able to inhibit TG2/PDI activities and specific protein kinases [3].   

Hypothesis and Objectives. We aim to 1) Refine new targets as novel therapeutic strategy in CF by exploiting a network of in silico and experimental approaches; 2) Validate the efficacy of novel drug candidates in pre-clinical CF models.