It was shown that changes in protein expression are clearly detectable after the silencing of the secondary targets, thus supporting the feasibility of our project. Indeed, seven and eleven proteins that are respectively up- and down-regulated following the abolition of the primary targets were identified. These proteins are considered as potential secondary targets. Also identified were four biological pathways that are significantly downregulated by the same CFTR rescuing maneuvers. Keeping safety concerns in mind, the authors selected a number of secondary targets and some of the key proteins for the downregulated pathways and silenced them in CFBE41o- models. Very promisingly, some of these proteins triggered a significant rescue of CFTR. In conclusion, with the use of proteomics and bioinformatics, it was identify a set of proteins (secondary targets) that, when silenced in CFBE410-, trigger a significant rescue of CFTR. The challenge is now to translate these results to primary cell cultures from CF patients, by modulating these targets by means of commercially available pharmacological modulators. The research will continue in the project FFC#1/2019.

Congress abstracts

• Braccia C, Proteomic profiling of mutated-CFTR expressing cells identify new pharmacological targets for cystic fibrosis, 3rd IMaSS Network Congress (Parma, Italy, May 2019)
• Braccia C, Tomati V, Caci E et al., Proteomic profiling of F508del-CFTR expressing cells to identify new pharmacological targets for cystic fibrosis, Proteomic Forum 2019, XIII. Annual Congress of the European Proteomics Association: From Genes via Proteins and their Interactions to FunctionsMarch 24–28, 2019, Potsdam, Germany