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UNC TCORS: The Effects of Tobacco Exposure on the Airway Proteome and Mucus/Mucin Integrity

Principal Investigator: Mehmet Kesimer

Funding Mechanism: National Institutes of Health- TCORS Grant

ID number: 1P50HL120100-01

Award Date: 9/19/2013

Institution: University of North Carolina Chapel Hill


Mucus is a complex network of mucins, antimicrobial peptides, enzymes and proteins that detect, immobilize, destroy, and/or remove a range of foreign bodies, toxins and pathological factors that would otherwise overwhelm the body’s defense system. Tobacco exposure dehydrates airway surfaces, and recent studies suggest that airway surface liquid (ASL) dehydration and reduced anion secretion may permanently alter mucin maturation. Investigators will analyze mucus from in vitro and in vivo models and from human subjects to identify novel biomarkers of tobacco exposure (mucomarkers) and to determine the effects of exposure to new and emerging tobacco products (e.g., flavored cigarettes, little cigars, hookah) on the expression of potential mucomarkers to assess the relative toxicology of these products. Airway epithelial cells will be derived from excess surgical pathology tissue from 63 elective surgery patients and from organ donor lungs not suitable for transplantation. Specific aims are: (1) to assess the impact of new and emerging tobacco products and their constituents on mucus/mucin biophysical and barrier properties, including their integrity, mucin polymeric structure, and maturation in mucus; (2) to identify mucomarkers in response to products with respect to both muco-proteome and mucin interactome in human bronchial cell cultures, mouse and human bronchoalveolar lavage fluid, and induced sputum; and (3) to test whether tobacco products change the proteins, messenger ribonucleic acid (mRNA), and microRNA (miR) contained in extracellular vesicles in responses to different tobacco products. This project will provide important information on the effect of tobacco exposure on mucus and its ability to protect airway surfaces.


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