Research

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

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. 

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.