In many cases, injury to the vocal fold results in fibrosis and dysphonia. Current therapies for these challenging patients are unsatisfactory, likely due to limited insight into the biochemical processes underlying vocal fold injury and repair. COX-2/PGE2 signaling is upregulated in fibrotic lesions in many tissues and has emerged as a target for antifibrotic therapy. In the larynx, our laboratory and others have reported upregulation of COX-2 and PGE2 in vocal fold injury and we now seek to expand these findings to determine the regulatory role of this signaling pathway in vocal fold injury and repair. In examining this pathway, we will examine key temporal and molecular switches related to vocal fold scarring that are suitable for pharmacological manipulation. Furthermore, we will obtain preliminary data regarding pharmacological inhibition of COX-2 as a means to facilitate a less fibrotic response following vocal fold injury. These findings are significant and have the potential for far-reaching scientific and clinical applications. Public Health Relevance: Fibrosis of the vocal folds is associated with significant morbidity. The current proposal seeks to investigate one regulatory signaling pathway in order to develop novel therapies for this challenging patient population.

Public Health Relevance

Branski, Ryan, Comfort Fibrosis of the vocal folds is associated with significant morbidity. The current proposal seeks to investigate one regulatory signaling pathway in order to develop novel therapies for this challenging patient population. PHS 398/2590 (Rev. 11/07) Page Continuation Format Page

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Small Research Grants (R03)
Project #
5R03DC010267-04
Application #
8209045
Study Section
Special Emphasis Panel (ZDC1-SRB-C (21))
Program Officer
Shekim, Lana O
Project Start
2009-07-09
Project End
2012-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
4
Fiscal Year
2011
Total Cost
$163,592
Indirect Cost
Name
New York University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Branski, Ryan C; Zhou, Hang; Kraus, Dennis H et al. (2011) The effects of cigarette smoke condensate on vocal fold transepithelial resistance and inflammatory signaling in vocal fold fibroblasts. Laryngoscope 121:601-5
Zhou, Hang; Sivasankar, Mahalakshmi; Kraus, Dennis H et al. (2011) Glucocorticoids regulate extracellular matrix metabolism in human vocal fold fibroblasts. Laryngoscope 121:1915-9
Zhou, Hang; Felsen, Diane; Sandulache, Vlad C et al. (2011) Prostaglandin (PG)E2 exhibits antifibrotic activity in vocal fold fibroblasts. Laryngoscope 121:1261-5
Branski, Ryan C; Zhou, Hang; Sandulache, Vlad C et al. (2010) Cyclooxygenase-2 signaling in vocal fold fibroblasts. Laryngoscope 120:1826-31