The larynx is uniquely located at the divergence of the upper and lower airways and gastrointestinal tract. The vocal folds are housed within the larynx and are the only tissues in the human body that routinely vibrate at frequencies ranging from ~100-1000 Hz, in order to generate voice.

Voice disorders affect millions of people every year and have a devastating impact on communication and quality of life. Our work is focused on laryngeal mucosal biology. Specifically, we investigate the cellular and molecular events leading to the development of voice disorders and seek to identify unique mechanisms involved in protection of the vocal fold mucosa from injury.

We actively seek to translate our research findings into practical applications for other voice scientists, clinicians, and patients with voice disorders.

Our investigative efforts are organized along four main research thrusts: 1) Laryngeal epithelial regeneration, 2) Laryngeal mucus production, 3) Laryngeal health effects of e-cigarettes, and 4) Novel interventions for voice disorders.

Laryngeal Epithelial Regeneration

Our laboratory has demonstrated pathological changes, or remodeling, in the composition and organization of the laryngeal epithelium in humans and animal models in response to exposure to inhaled tobacco products insults, notably cigarette smoke (CS). Remodeling affects the ability of the epithelium to function as an effective barrier and likely predisposes the tissue to disease development. CS has been implicated in the pathogenesis of multiple vocal fold diseases. Despite the prevalence and likely importance of epithelial remodeling in CS-induced laryngeal disease, its etiology is poorly understood. This is due to a lack of basic knowledge of the mechanisms which dictate laryngeal epithelial regeneration versus permanent tissue remodeling linked to CS. Specifically, little is known about the biology of the basal cell (BC) population, a reservoir of progenitor cells in the laryngeal epithelium. 

We are testing whether BC are critical to normal laryngeal epithelial regeneration and whether CS-induced alterations in BC biology are associated with epithelial remodeling and disease development. Studies on human tissue specimens alone cannot offer insight into the full trajectory of the role of BC in laryngeal regeneration as well as injury and disease development. Consequently, we use novel in vivo and in vitro models of CS exposure developed in our laboratory to study laryngeal BC properties in differentiated epithelium, primary culture, and physiologically relevant three-dimensional epithelial cell culture systems

Laryngeal Mucus Production

The vocal folds are exposed to ~25 million pollutant, viral, and bacterial insults each day and require protection from this myriad of inhaled insults. Mucus is the thin layer of fluid that covers the surface of the vocal folds and is the first line of defense in the larynx. However, an increased amount of thick, tacky mucus is commonly observed on the vocal folds in persons with inflammatory voice disorders. This phenomenon, described as “mucus aggregation,” is not trivial. Mucus aggregation is one of the most common complaints of persons with voice disorders and leads to phonotraumatic behaviors, negatively impacts vocal fold vibration and voice quality, and may even promote the accumulation of noxious irritants in the larynx. 

Currently, a major obstacle in treating mucus aggregation is that biological mechanisms regulation laryngeal mucus production in normal or inflamed larynges are not known. We are actively seeking to elucidate cellular and molecular mechanisms underlying laryngeal mucus production and to assess clinical mucus aggregation and vocal function during normal and inflammatory conditions.  Our findings add to the knowledge base necessary to develop strategies to normalize the laryngeal mucus layer. Such strategies will likely not only have a positive impact on voice production, but also overall laryngeal health. 

Laryngeal Health Effects of E-Cigarettes

E-cigarettes (e-cigs) are popular recreational tools among adolescents and adults and the use of these products continue to accelerate at an alarming pace. E-cigs are battery-powered devices designed to produce a vapor, which is inhaled by the user. These devices work by heating and aerosolizing a liquid mixture typically consisting of propylene glycol (PG) and vegetable glycerin (VG), mixed with varying concentrations of nicotine and flavors. The epithelial surfaces of the respiratory tract, including the larynx, are the first set of tissues to receive this assault. Despite its critical functions, the larynx is a significantly understudied region of the respiratory tract and the effect of e-cigs on laryngeal health is almost entirely unknown. There is a lack of evidence for the safety of these devices, and it is likely e-cigs pose a significant potential health threat to the larynx. In addition, e-cigs may provide a pathway to smoking conventional cigarettes, a major cause of preventable harm in the larynx. Our long-term goal is to elucidate the effects of e-cigs on laryngeal health. Consequently, we have developed in vivo mouse and in vitro cell culture models of e-cig exposure that are used to study the pathophysiological changes that may occur in the larynx of human e-cig users.

Elucidating the effects of e-cigs on biological mechanisms that contribute to the development of laryngeal disease is of significance for making informed clinical recommendations regarding the use of these products.

Novel Interventions for Voice Disorders

We are also interested in clinical and quality of life outcomes in patients with voice disorders undergoing surgical or behavioral interventions. One area of current focus is developing novel interventions for essential vocal tremor (EVT). Deep brain stimulation (DBS) of the thalamus has emerged as a leading and effective surgical intervention for essential tremor of the limbs. However, the effects of DBS treatment on EVT are almost entirely unknown. 

The objective of this project to the evaluate the effect of DBS on physiologic, acoustic, and perceptual measures of EVT. Results of this work will provide evidence regarding the promising application of DBS to address EVT in patients with essential tremor and have the potential to alter treatment paradigms for these difficult-to-serve patients.