Eugene Chang
Associate Professor, BIO5 Institute
Associate Professor, Clinical Translational Sciences
Associate Professor, Neurosurgery
Associate Professor, Otolaryngology
Member of the Graduate Faculty
Vice Chair, Academic Affairs - Otolaryngology
Primary Department
Department Affiliations
(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

Le, C., McCrary, H. C., & Chang, E. (2016). Cystic Fibrosis Sinusitis. Advances in oto-rhino-laryngology, 79, 29-37.

Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by mutations in the CF transmembrane conductance regulator gene(CFTR) resulting in impaired ion transport. Nearly all people with CF will develop chronic rhino-sinusitis (CRS) and present with the characteristic viscous mucus, impaired mucociliary clearance and chronic inflammation/infection of the sinonasal cavity. While some individuals with CF can appear relatively asymptomatic in terms of their sinus disease, commonly reported symptoms include anosmia, headache, facial pain, nasal obstruction, chronic congestion and nasal discharge. Nasal endoscopy typically reveals mucosal edema, purulent discharge and nasal polyposis. Computed tomography (CT) imaging classically demonstrates the distinguishing findings of sinus hypoplasia or aplasia with generalized opacification, medial bulging of the lateral sinonasal sidewall and a demineralized uncinate process. Current treatment for CF sinusitis includes the use of hypertonic saline, topical and systemic steroids, antibiotics and endoscopic surgery. Research investigating novel therapies designed at targeting the primary defect of CF is showing promise for reversal of CF sinus disease, in addition to potential for disease prevention.

Fletcher, A., Choi, J., Awadalla, M., Potash, A. E., Wallen, T. J., Fletcher, S., & Chang, E. H. (2013). The effect of geniglossal advancement on airway flow using a computational flow dynamics model. The Laryngoscope, 123(12), 3227-32.

Obstructive sleep apnea (OSA) is a sleep disorder caused by partial or complete collapse of the pharyngeal airway. Genioglossal advancement (GGA) is a well-tolerated surgical procedure intended to address hypopharyngeal collapse, yet there are few studies that monitor changes in airflow dynamics at this site. Computation fluid dynamics (CFD) utilizes airflow simulation to predict changes in airflow after anatomic manipulation.

Chang, E. H., & Hamilton, G. S. (2008). Novel technique for peritonsillar abscess drainage. The Annals of otology, rhinology, and laryngology, 117(9), 637-40.

We propose a novel technique for peritonsillar abscess (PTA) drainage in which the patient is lying in the Trendelenburg position. We provide evidence that this novel technique is relatively safe and effective in PTA drainage.

Potash, A. E., Wallen, T. J., Karp, P. H., Ernst, S., Moninger, T. O., Gansemer, N. D., Stoltz, D. A., Zabner, J., & Chang, E. H. (2013). Adenoviral gene transfer corrects the ion transport defect in the sinus epithelia of a porcine CF model. Molecular therapy : the journal of the American Society of Gene Therapy, 21(5), 947-53.

Cystic fibrosis (CF) pigs spontaneously develop sinus and lung disease resembling human CF. The CF pig presents a unique opportunity to use gene transfer to test hypotheses to further understand the pathogenesis of CF sinus disease. In this study, we investigated the ion transport defect in the CF sinus and found that CF porcine sinus epithelia lack cyclic AMP (cAMP)-stimulated anion transport. We asked whether we could restore CF transmembrane conductance regulator gene (CFTR) current in the porcine CF sinus epithelia by gene transfer. We quantified CFTR transduction using an adenovirus expressing CFTR and green fluorescent protein (GFP). We found that as little as 7% of transduced cells restored 6% of CFTR current with 17-28% of transduced cells increasing CFTR current to 50% of non-CF levels. We also found that we could overcorrect cAMP-mediated current in non-CF epithelia. Our findings indicate that CF porcine sinus epithelia lack anion transport, and a relatively small number of cells expressing CFTR are required to rescue the ion transport phenotype. These studies support the use of the CF pig as a preclinical model for future gene therapy trials in CF sinusitis.

Chang, E. H., Pezzulo, A. A., Meyerholz, D. K., Potash, A. E., Wallen, T. J., Reznikov, L. R., Sieren, J. C., Karp, P. H., Ernst, S., Moninger, T. O., Gansemer, N. D., McCray, P. B., Stoltz, D. A., Welsh, M. J., & Zabner, J. (2012). Sinus hypoplasia precedes sinus infection in a porcine model of cystic fibrosis. The Laryngoscope, 122(9), 1898-905.

Chronic sinusitis is nearly universal in humans with cystic fibrosis (CF) and is accompanied by sinus hypoplasia (small sinuses). However, whether impaired sinus development is a primary feature of loss of the cystic fibrosis transmembrane conductance regulator (CFTR) or a secondary consequence of chronic infection remains unknown. Our objective was to study the early pathogenesis of sinus disease in CF.