Developed skills and lines of research
Nicoletta Pedemonte has a strong expertise in drug discovery strategies and functional
genomics. In the last 2 decades she has been actively involved in various research
projects focused on drug discovery for CF. She has a major expertise on the mechanisms
of transepithelial ion transport in airway epithelial cells and in the field of CFTR
pharmacology, with several pivotal publications reporting the identification and
characterization of CFTR correctors and potentiators by high-throughput methods and
their evaluation in native epithelial cells.
During her activities, she adopted RNAi as an additional strategy to support her studies.
She applied the screening of siRNA libraries as a functional genomics strategy to identify
other chloride channel proteins and to dissect the CFTR interactome. This latter project led
to the discovery of proteostasis regulators that have the potential to lead to innovative new
therapies for CF.
Later, her studies focused to understand the changes, at the cell proteome and lipidome
level, determined by the presence of CFTR mutations, and to evaluate secondary effects
of modulator drugs.
Since 2019 she has been coordinating a theratyping project aiming to characterize, in a
native cell context, rare CFTR mutations and to evaluate their response to approved and
novel modulators.
She has been the recipient of various research grants awarded by the Italian Cystic
Fibrosis Foundation, the AFM Telethon, the Jerome Lejeune Foundation, the Italian
Ministry of Health, and the Cystic Fibrosis Foundation.
Since March 2022, she has served as Deputy Scientific Director of the Italian Cystic
Fibrosis Research Foundation.
Projects funded by FFC Ricerca as Principal Investigator or as Research Manager
FFC#10/2021
Theratyping orphan mutations in Italian cystic fibrosis patients: meeting unmet needs
FFC#9/2019
Theratyping orphan mutations in Italian cystic fibrosis patients: efficacy of CFTR modulators and RNF5 inhibitors
FFC#9/2017
RNF5 inhibitors as potential drugs for Cystic Fibrosis basic defect
FFC#5/2012
Modulation of post-translational modification and quality control system as a novel therapeutic strategy for Cystic Fibrosis
FFC#3/2009
Dissection by RNAi-mediated silencing of molecular mechanism leading to F508del-CFTR misprocessing
Projects financed by FFC Ricerca as a partner
FFC/TFCF fase preclinica
Task Force for Cystic Fibrosis
FFC#2/2015
RNF5/RMA1 ubiquitin ligase as a drug target for mutant CFTR rescue
Publications from FFC Research projects
Pedemonte N, Diena T, Caci E et al. Antihypertensive 1,4-dihydropyridines as correctors of the cystic fibrosis transmembrane conductance regulator channel gating defect caused by cystic fibrosis mutations. Mol Pharmacol. 2005 Dec;68(6):1736-46. Epub 2005 Sep 8.
Pedemonte N1, Lukacs GL, Du K et al. Small-molecule correctors of defective DeltaF508-CFTR cellular processing identified by high-throughput screening. J Clin Invest. 2005 Sep;115(9):2564-71. Epub 2005 Aug 25.
Pedemonte N, Tomati V, Sondo E, et al. Dual activity of aminoarylthiazoles on the trafficking and gating defects of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel caused by cystic fibrosis mutations. J Biol Chem, 2011 Apr 29;286(17):15215-26. doi: 10.1074/jbc.M110.184267. Epub 2011 Mar 7.
Tomati V, Sondo E, Amirotti A, et al. Genetic Inhibition Of The Ubiquitin Ligase Rnf5 Attenuates Phenotypes Associated To F508del Cystic Fibrosis Mutation. Sci Rep, 2015 Jul 17;5:12138. doi: 10.1038/srep12138.
Tomati V, Pesce E, Caci E et al. High-throughput screening identifies FAU protein as a regulator of mutant cystic fibrosis transmembrane conductance regulator channel. J Biol Chem. 2018 Jan 26;293(4):1203-1217. doi: 10.1074/jbc.M117.816595. Epub 2017 Nov 20.
Li H, Pesce E, Sheppard DN et al. Therapeutic approaches to CFTR dysfunction: From discovery to drug development. J Cyst Fibros. 2017 Sep 12. pii: S1569-1993(17)30876-7. doi: 10.1016/j.jcf.2017.08.013. [Epub ahead of print].
Sondo E, Falchi F, Caci E, et al. Pharmacological Inhibition of the Ubiquitin Ligase RNF5 Rescues F508del-CFTR in Cystic Fibrosis Airway Epithelia. Cell Chem Biol. 2018 Jul 19;25(7):891-905.e8. doi: 10.1016/j.chembiol.2018.04.010. Epub 2018 May 10.
Tomati V, Caci E, Ferrera L, et al. Thymosin α-1 does not correct F508del-CFTR in cystic fibrosis airway epithelia. JCI Insight. 2018 Feb 8;3(3). pii: 98699. doi: 10.1172/jci.insight.98699. eCollection 2018 Feb 8.
Miquéias Lopes-Pacheco, Nicoletta Pedemonte, Anthony Kicic. Editorial: Emerging Therapeutic Approaches for Cystic Fibrosis. Front Pharmacol, 10, 1440 2019 Nov 29 eCollection 2019