It is estimated that the annual cost of the treatment for voice disorders in the United States is between $11.9- 13.5 billion. A significant contributor o the development of benign vocal fold disease, such as nodules, polyps, and cysts, is phonotrauma. In severe cases, benign vocal fold disease can result in dysphonia with reduced overall quality of life and compromised communication function. The vocal fold epithelial barrier is critical in maintaining the integrity of the vocal folds. During acute episodes of phonotrauma, the epithelial barrier structure and function are severely compromised. The current strategic plan of the National Institute on Deafness and Other Communication Disorders has acknowledged that laryngeal structure and function changes and mechanisms underlying disorders resulting from phonotrauma are priority areas of research. The objective of the proposed research is to test a theory regarding how vocal fold epithelial barrier disruption occurs. The theory reasons that the biomechanical stresses during phonotrauma signal apoptosis, or programmed cell death. Preliminary studies from our laboratory demonstrate that apoptosis signaling occurs along the apical cell surface of the vocal fold epithelium after acute phonotrauma. This finding has led to the overarching hypothesis that apoptosis signaling in the vocal fold epithelium increases with longer time-doses and larger magnitude-doses of vibration exposure. If this hypothesis is supported, the proposed research will provide empirical evidence for a specific signaling pathway involved in vocal fold epithelial barrier disruption.
The specific aim of the proposed research is (1) to measure the effects of increasing time-dose and magnitude-dose of vibration exposure on apoptosis signaling in the vocal fold epithelium.
This aim will be addressed using a number of approaches that are highly innovative to this field, including terminal deoxynucleotidyl transferase dUTP nick end labeling assay staining, caspase-3 staining, and transmission electron microscopy. If the hypothesis is correct, findings will provide novel evidence for a specific mechanism that is responsible for the maintenance of the vocal fold epithelial barrier. It is anticipated that this work will provide a solid foundation of critical knowledge for a programmatic line of research focusing on the development of therapeutic approaches to regulate apoptosis and preserve the integrity of the vocal fold epithelial barrier in patients with benign vocal fold disease.

Public Health Relevance

Individuals with voice disorders experience substantial communication impairments and reduced quality of life. It is imperative to better understand the biological and cellular mechanisms involved in vocal fold vibration to develop improved interventions for voice problems. The overarching objective of this work is to improve the prevention, diagnosis, and treatment for voice disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31DC014621-01A1
Application #
8981151
Study Section
Special Emphasis Panel (ZDC1)
Program Officer
Rivera-Rentas, Alberto L
Project Start
2015-05-01
Project End
2017-04-30
Budget Start
2015-05-01
Budget End
2016-04-30
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Other Health Professions
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37240
Novaleski, Carolyn K; Carter, Bruce D; Sivasankar, M Preeti et al. (2017) Apoptosis and Vocal Fold Disease: Clinically Relevant Implications of Epithelial Cell Death. J Speech Lang Hear Res 60:1264-1272
Novaleski, Carolyn K; Mizuta, Masanobu; Rousseau, Bernard (2016) Evaluation of Dying Vocal Fold Epithelial Cells by Ultrastructural Features and TUNEL Method. Cells Tissues Organs 202:355-368
Novaleski, Carolyn K; Kimball, Emily E; Mizuta, Masanobu et al. (2016) Acute exposure to vibration is an apoptosis-inducing stimulus in the vocal fold epithelium. Tissue Cell 48:407-16