ABSTRACT
Clinically, atrophy of the intrinsic laryngeal musculature is poorly defined likely related to limited understanding
of fundamental biological processes underlying this complex, aberrant tissue phenotype. This lack of insight
underlies suboptimal therapeutic strategies for these challenging patients. In addition to fundamental
investigation regarding this phenotype, we hypothesize that initiation and maintenance of atrophy of the
intrinsic laryngeal musculature is related to signaling events in the mucosa. Specifically, our laboratory
elucidated the role of TGF-ß signaling with an emphasis on therapeutic strategies targeting the SMAD family of
signaling proteins in the vocal fold lamina propria. SMADs, however, also mediate muscle atrophy in other
systems, specifically through regulation of atrogenes and myostatin, a member of the TGF-ß superfamily. We
hypothesize that the inherent response to injury in the lamina propria elicits and/or enhances an atrophic in the
muscle. This concept is inherently innovative in that it refutes clinical dogma suggesting the vocal fold mucosa
and muscle of the vocal folds operate as wholly separate and distinct entities. In that regard, we propose to
interrogate fundamental and functional laryngeal muscle outcomes of recurrent laryngeal nerve injury-mediated
thyroarytenoid atrophy in the context of both acute and chronic mucosal injury. In addition, we seek to
interrogate key biochemical relationships and interactions between multiple cell types from the vocal folds to
provide foundational insight into processes underling atrophy. And finally, we seek to provide preliminary data
related to therapeutic strategies to prevent/treat laryngeal muscle atrophy targeting SMAD signaling.
Ultimately, these data represent substantive contributions to the literature and are foundational for the
development of novel treatment strategies for millions of patients with disability related to voice disorders and
laryngeal disease.