The goals of this proposal are to investigate the mechanisms that regulate vocal fold epithelial functions, and to examine the role of the epithelium in maintaining the biological and mechanical properties of vocal fold connective tissue and muscle. The epithelium lies at the interface between the environment and connective tissue. As the outermost layer of the vocal folds, the epithelium is routinely exposed to noxious, inhaled and systemic challenges. The extent to which these challenges adversely affect epithelial functions, and the consequences of epithelial dysfunction on compromising the biological and mechanical properties of underlying connective tissue and muscle have not been investigated. These are critical questions because compromised properties of connective tissue and muscle result in dysphonia, and systemic and inhaled challenges are thought to increase the vulnerability to voice disorders. This proposal will quantify the role of the epithelium in protecting underlying tissue, by exposing vocal fold epithelia to challenges and investigating the ramifications of epithelial dysfunction on connective tissue and muscle. Reflux and pollutants will serve as representative challenges, because vocal fold epithelia are exposed to gastric reflux and pollution during daily activities. The proposed research is significant to the area of voice disorders because it systematically examines the adverse consequences of challenges at relevant dosages, on the entire vocal fold (epithelium, connective tissue, and muscle). The three foci of the proposal are: to characterize the mechanisms that regulate epithelial barrier function and epithelial ion transport function;to determine whether realistic challenge exposures at relevant dosages disrupt epithelial functions;and to investigate the consequences of epithelial dysfunction on connective tissue and muscle. The prospective, blinded experiments proposed here will combine electrophysiological, molecular, histological, and biomechanical approaches to yield data that are important for several reasons. First, data will demonstrate the adverse effects of common challenges on the phonatory system. Second, data will demonstrate the extent to which the epithelium protects underlying connective tissue and muscle. Third, data will highlight one pathway for epithelial-connective tissue interaction. Altogether, the findings will shed light on the role of vocal fold epithelium in maintaining the homeostasis of underlying layers in a challenging environment. Additionally, the findings will lay the groundwork for pharmacological treatments and tissue regenerative strategies to focus on strengthening and restoring epithelial function, to protect underlying connective tissue and muscle, and prevent dysphonia.

Public Health Relevance

The vocal fold epithelium is exposed to noxious challenges from the environment. This application will investigate the role of the epithelium in protecting connective tissue and muscle from these challenges. The long-term goal is to understand the underlying mechanisms for negative voice changes resulting from exposure to these challenges, and to develop treatments that restore vocal fold structure and function.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Study Section
Motor Function, Speech and Rehabilitation Study Section (MFSR)
Program Officer
Shekim, Lana O
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Purdue University
Other Health Professions
Schools of Arts and Sciences
West Lafayette
United States
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Oleson, Steven; Lu, Kun-Han; Liu, Zhongming et al. (2018) Proton density-weighted laryngeal magnetic resonance imaging in systemically dehydrated rats. Laryngoscope 128:E222-E227
Liu, Xinxin; Durkes, Abigail C; Schrock, William et al. (2018) Subacute acrolein exposure to rat larynx in vivo. Laryngoscope :
Liu, Xinxin; Mustonen, Allison; Zheng, Wei et al. (2018) Cigarette Smoke Exposure to Pig Larynx in an Inhalation Chamber. J Voice :
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Liu, Xinxin; Walimbe, Tanaya; Schrock, William Pierre et al. (2017) Acute Nanoparticle Exposure to Vocal Folds: A Laboratory Study. J Voice 31:662-668
Walimbe, Tanaya; Panitch, Alyssa; Sivasankar, Preeti M (2017) A Review of Hyaluronic Acid and Hyaluronic Acid-based Hydrogels for Vocal Fold Tissue Engineering. J Voice 31:416-423
Liu, Xinxin; Zheng, Wei; Sivasankar, M Preeti (2016) Acute Acrolein Exposure Induces Impairment of Vocal Fold Epithelial Barrier Function. PLoS One 11:e0163237
Durkes, Abigail; Sivasankar, M Preeti (2016) In vivo investigation of acidified pepsin exposure to porcine vocal fold epithelia. Laryngoscope 126:E12-7
Erickson-DiRenzo, Elizabeth; Sivasankar, M Preeti; Thibeault, Susan L (2015) Utility of cell viability assays for use with ex vivo vocal fold epithelial tissue. Laryngoscope 125:E180-5

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