Silvia M. Kreda Ph.D.


Silvia M Kreda, PhD Assistant Professor of Medicine CF Center/Marsico lung Institute The University of North Carolina at Chapel Hill I am a faculty member of the UNC CF Center for almost twenty years. The research of my lab focusses on three main aspects of airway epithelial biology to understand CF pathogenesis and design novel therapeutic approaches. One line of investigation focusses on the regulation of expression of epithelial CFTR. Another main research interest of my lab is the exocytotic mechanisms in airway epithelium, specifically the regulation of mucin granule exocytosis and mucus formation, as a means to therapeutically reduce mucin secretion and mucus obstruction in CF lung disease. A third line of research addresses the mechanisms of delivery of therapeutic drugs to intracellular epithelial targets, which is a main obstacle for many lung therapeutic agents. Consequently, our studies aim to understand the epithelial barriers that interfere with the delivery into the epithelial surface and the intracellular internalization of potential therapeutic agents. We designed one of the few successful receptor-targeted strategies for gene therapy vectors, which can overcome the apical membrane barrier and translated in efficient gene transfer in primary airway epithelial cultures. Our lab was pioneer in using oligonucleotides as experimental agents to modified or correct expression in airway epithelial cells. Moreover, we continue studying mechanisms of apical entry and subcellular trafficking to facilitate therapeutic drug delivery in CF and other lung diseases. These studies encompass collaborative efforts with academic labs and pharma for 10+ years. Currently, in collaboration with Dr. Rudolph Juliano (UNC), we are investigating a novel strategy to effectively deliver therapeutic oligonucleotides to correct CF splice mutations, as well as other rare CFTR mutations that can be aided by oligonucleotide therapy. a. Kreda, SM & Gentzsch, M. Imaging CFTR Protein Localization in Cultured Cells and Tissues (2011) Methods Mol Biol 742, 15-33 b. Kreda, SM; Davis, CW; Rose, MC. CFTR, mucins, and mucus obstruction in cystic fibrosis (2012) In: Cold Spring Harb Perspect Med : Cystic Fibrosis 2(9): a009589 PMC3426818 c. Kreda SM, Boucher RC, Lazarowski ER. Nucleotide release and airway physiology (2008) Physiology News 71:19-21 d. Lazarowski ER, Sesma J, Seminario L, and Kreda SM Molecular mechanisms of purine and pyrimidine nucleotide release In Purines; Jacobson K and Lindel J, Edts (2011) Adv Pharmacol 61:221-61 d. EnviroNews article (2001) Complete List of Published Work in My Bibliography: