The universality of fibrosis as an underlying etiology for many voice disorders stems from the reparative response to injury. To date, treatments have been largely unsatisfactory. Acknowledging that healing is complex, we seek to expand our recent findings elucidating one regulatory mechanism underlying repair in the vocal folds. Specifically, we seek increased insight into the transforming growth factor (TGF)-? signaling cascade. Our preliminary data suggest that targeting this pathway, not TGF-? directly, but rather upstream, to be optimal. Smad3, an upstream cytoplasmic signaling protein provides an ideal target for the use of RNA- based therapeutics, specifically small interfering ribonucleic acid (siRNA). However, delivery of siRNA in vivo is complicated by the inherent proteolytic environment. We hypothesize that lipid nanoparticle delivery will address these issues, delivering optimal drug concentrations with reduced toxicity. This investigation is germane;cumulative estimates regarding the incidence of voice disorders across the lifespan are not known, but are hypothesized to be higher than the 3-9% of the population figure that is often cited. This innovative approach has potential to evolve to the clinic across multiple organ systems.

Public Health Relevance

Vocal fold fibrosis is a source of common, debilitating voice disorders and treatments remain unsatisfactory. We seek to employ RNA-based therapeutics and furthermore optimize in vivo delivery of these compounds with the ultimate goal of facilitating a more regenerative model of healing in the vocal folds.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Motor Function, Speech and Rehabilitation Study Section (MFSR)
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Shekim, Lana O
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New York University
Schools of Medicine
New York
United States
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Hiwatashi, Nao; Kraja, Iv; Benedict, Peter A et al. (2018) Nanoparticle delivery of RNA-based therapeutics to alter the vocal fold tissue response to injury. Laryngoscope 128:E178-E183
Mukudai, Shigeyuki; Hiwatashi, Nao; Bing, Renjie et al. (2018) Phosphorylation of the glucocorticoid receptor alters SMAD signaling in vocal fold fibroblasts. Laryngoscope :
Dion, Gregory R; Benedict, Peter A; Coelho, Paulo G et al. (2018) Impact of medialization laryngoplasty on dynamic nanomechanical vocal fold structure properties. Laryngoscope 128:1163-1169
Hiwatashi, Nao; Mukudai, Shigeyuki; Bing, Renjie et al. (2018) The effects of cytosporone-B, a novel antifibrotic agent, on vocal fold fibroblasts. Laryngoscope 128:E425-E428
Hiwatashi, Nao; Bing, Renjie; Kraja, Iv et al. (2017) NR4A1 is an endogenous inhibitor of vocal fold fibrosis. Laryngoscope 127:E317-E323
Hiwatashi, Nao; Benedict, Peter A; Dion, Gregory R et al. (2017) SMAD3 expression and regulation of fibroplasia in vocal fold injury. Laryngoscope 127:E308-E316
Kraja, Iv; Bing, Renjie; Hiwatashi, Nao et al. (2017) Preliminary study of a novel transfection modality for in vivo siRNA delivery to vocal fold fibroblasts. Laryngoscope 127:E231-E237
Dion, Gregory R; Coelho, Paulo G; Teng, Stephanie et al. (2017) Dynamic nanomechanical analysis of the vocal fold structure in excised larynges. Laryngoscope 127:E225-E230
Hiwatashi, Nao; Bing, Renjie; Kraja, Iv et al. (2017) Mesenchymal stem cells have antifibrotic effects on transforming growth factor-?1-stimulated vocal fold fibroblasts. Laryngoscope 127:E35-E41
Dion, Gregory R; Jeswani, Seema; Roof, Scott et al. (2016) Functional assessment of the ex vivo vocal folds through biomechanical testing: A review. Mater Sci Eng C Mater Biol Appl 64:444-453

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