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Luis JV. Galietta, MSc - "Therapeutic strategies to correct the basic defect in cystic fibrosis"

Principal Investigator and Head of Cell Culture and Cytogenetics Core, Tigem, Naples, Italy
When Dec 18, 2018
from 12:00 PM to 01:30 PM
Where Tigem, Vesuvius Auditorium
Contact Name
Contact Phone 081-19230659
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Abstract
Cystic fibrosis (CF), one of the most frequent genetic diseases (approximately 6,000 patients in Italy), is caused by the defective function of CFTR, an epithelial anion channel.  Loss of chloride and bicarbonate secretion leads to a multi-organ disease that is particularly severe in the lungs.  Here, loss of CFTR causes impairment of antimicrobial defense mechanisms with consequent development of airway colonization by antibiotic-resistant bacteria.
Mutant CFTR protein can ben rescued with small molecules that can target the different defects caused by CF mutations.  One of our goals is to find novel “correctors”, i.e. small molecules that improve the folding, stability, and trafficking of CFTR with F508del or other similar mutations.  Recently, we identified compounds that, in combination with first generation correctors, markedly enhance chloride secretion in bronchial and nasal epithelial cells from CF patients.
A second goal of our studies is to develop alternative therapeutic strategies in CF.  For this purpose, we are considering two alternative targets.  The first target, TMEM16A, is another type of anion channel expressed in epithelial cells.  Its pharmacological stimulation could represent a strategy to bypass CF basic defect.  Recently, we screened a chemical library with the identification of putative TMEM16A activators.  These compounds are now under evaluation.  The second target, ATP12A, acts as a proton/potassium pump.  Its activity leads to abnormal acidification of CF airways.  We are studying ATP12A expression/role in the airway epithelium and developing a suitable functional assay with the final goal to identify pharmacological inhibitors.  These compounds could become novel drugs to normalize pH in the airways of CF patients.

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