Khalequz Zaman

Zaman, Khalequz


  • PhD, Jagiellonian University

Contact Information

PO Box 800386
Telephone: 434-982-4144

Research Interests

S-Nitrosylation signaling in cystic fibrosis airway.

Research Description

Cystic fibrosis (CF), is a multisystem disease associated with in the gene that encodes the cystic fibrosis transmembrane conductance regulatory (CFTR) protein. The most common mutation associated with CF, ΔF508, results in a single amino acid phenylalanine deletion. The majority of wild type CFTR and virtually all δF508 CFTR is degraded before reaching the cell surface. Certain agents and conditions that increase expression and maturation of ΔF508 CFTR enable the protein to function at the cell surface. Therefore, there is an interest in identifying compounds with a favorable pharmacological profile that could have this effect in vivo, reversing the molecular defect and preventing disease progression. The long-term goal of our laboratory is to elucidate the molecular mechanisms by which different S-nitrosothiols up-regulates the expression, maturation and function of ΔF508 CFTR in cystic fibrosis airway epithelial cells. S-nitrosothiols are endogenous bronchodilators and signaling molecules which are normally present in the human airway and tend to be low concentrations in the cystic fibrosis airway. Because S-nitrosothiols concentrations are low in the airways of cystic fibrosis patients which indicate that these compounds are relevant for the proper functioning of airways. From our laboratory, we previously demonstrated that aerosol therapy with GSNO is well tolerated and improves oxygenation in CF patients. We and others have also demonstrated that different S-nitrosothiols at physiological concentrations increase expression, maturation and function of mutant ΔF508 CFTR  in different non-polarized and polarized cell lines in part through inhibition of a molecular co-chaperone Hsp70/Hsp90 organizing protein (Hop) expression.  These data show different S-nitrosothiols are potentially interesting candidates for pharmacologic treatment of cystic fibrosis.

Selected Publications