Eugene Chang

Eugene Chang

Associate Professor, Otolaryngology
Vice Chair, Academic Affairs - Otolaryngology
Associate Professor, Clinical Translational Sciences
Associate Professor, Neurosurgery
Member of the Graduate Faculty
Associate Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 626-6673

Research Interest

Dr. Chang’s research is divided into three areas.Cystic fibrosis (CF) research: Dr. Chang is investigating the role of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in the pathogenesis of chronic sinusitis. He published the first animal model of CF sinus disease, and has characterized novel therapies including gene therapy vectors and CFTR potentiators in improving CF sinus disease in both animals and humans.Sinus microbiome research: the “microbiome” is the microbial community that is present in the human body. The sinonasal cavities have traditionally been thought to be sterile cavities, but new research is beginning to elucidate the vast number of microbial communities that populate our sinus. With this knowledge, we are investigating how our current therapies can influence this microbial population and prevent sinus disease.Impact of the upper and lower airway: as otolaryngologists, our focus has been in the airway of the head and neck. Dr. Chang has been investigating how the upper airway can influence disease of the lower airway, and vice versa. This research can influence the understanding of common diseases of the lower airway, such as asthma and chronic obstructive pulmonary disease (COPD).Dr. Chang receives active funding research support from the NIH, and the Cystic Fibrosis Foundation.

Publications

Willis, A. L., Calton, J. B., Carr, T. F., Chiu, A. G., & Chang, E. H. (2016). Differentiating live from dead: a novel profile of the sinus microbiome.. American Journal of Rhinology and Allergy.
Stoltz, D. A., Rokhlina, T., Ernst, S. E., Pezzulo, A. A., Ostedgaard, L. S., Karp, P. H., Samuel, M. S., Reznikov, L. R., Rector, M. V., Gansemer, N. D., Bouzek, D. C., Alaiwa, M. H., Hoegger, M. J., Ludwig, P. S., Taft, P. J., Wallen, T. J., Wohlford-Lenane, C., McMenimen, J. D., Chen, J., , Bogan, K. L., et al. (2013). Intestinal CFTR expression alleviates meconium ileus in cystic fibrosis pigs. The Journal of clinical investigation, 123(6), 2685-93.

Cystic fibrosis (CF) pigs develop disease with features remarkably similar to those in people with CF, including exocrine pancreatic destruction, focal biliary cirrhosis, micro-gallbladder, vas deferens loss, airway disease, and meconium ileus. Whereas meconium ileus occurs in 15% of babies with CF, the penetrance is 100% in newborn CF pigs. We hypothesized that transgenic expression of porcine CF transmembrane conductance regulator (pCFTR) cDNA under control of the intestinal fatty acid-binding protein (iFABP) promoter would alleviate the meconium ileus. We produced 5 CFTR-/-;TgFABP>pCFTR lines. In 3 lines, intestinal expression of CFTR at least partially restored CFTR-mediated anion transport and improved the intestinal phenotype. In contrast, these pigs still had pancreatic destruction, liver disease, and reduced weight gain, and within weeks of birth, they developed sinus and lung disease, the severity of which varied over time. These data indicate that expressing CFTR in intestine without pancreatic or hepatic correction is sufficient to rescue meconium ileus. Comparing CFTR expression in different lines revealed that approximately 20% of wild-type CFTR mRNA largely prevented meconium ileus. This model may be of value for understanding CF pathophysiology and testing new preventions and therapies.