<p>Vocal fold vibration results in voice production. Optimal hydration levels contribute to self-sustained vocal fold vibration and preservation of voice quality. Adequate hydration is implicated as a factor in maintaining voice and preventing voice problems. Voice problems affect up to one third of adults during their lifetime. But whether altered hydration state adversely affects vocal fold biology and biomechanics is still unclear. To untangle the effects of systemic dehydration on vocal fold biology, we developed a water restriction protocol on lab animals that can translate to humans. Our results showed that dehydration induced by restricted water access downregulated the gene expression of IL-1α and desmoglein-1, upregulated the gene expression level of hyaluronidase-2, and downregulated hyaluronic acid (HA).</p> <p>Clinically, hydration treatments are hypothesized to maintain the viscoelastic properties of vocal folds. However, our understanding of the relationship between vocal fold tissue hydration level and biomechanical properties is still evolving. To investigate the effects of dehydration on biomechanical properties we used an ex vivo experimental design. We hypothesized that the optimal stiffness of vocal folds would be impacted after dehydration via losing both water and HA, but that the stiffness properties would recover through rehydration. To test this hypothesis, we experimentally treated porcine vocal fold samples using two different approaches: 1) immersion in hypertonic solution (15% NaCl in ddH2O) and PBS sequentially to mimic dehydration and rehydration, and 2) incubation with hyaluronidase (Hyal) to mimic HA loss during dehydration. Our results showed that loss of water increased tissue stiffness and could be recovered through rehydration in a certain degree. In addition, loss of HA increased tissue stiffness. </p> <p>In While dehydration decreases total body blood volume, different tissues and organs of the body may be impacted in different ways from dehydration. Therefore, it is important to investigate the hemodynamic alterations during changes to hydration status. Magnetic resonance angiography (MRA) and ultrasound imaging were employed to identify the delicate vascular geometry and hemodynamics of the laryngeal blood supply. Animals underwent both MRA and ultrasound imaging at baseline, dehydration and rehydration time points. Our results showed that dehydration impacted the blood supply to larynx. This blood supply was restored through rehydration treatment.</p> <p>Overall, this research has been successful in establishing a mild dehydration animal model, providing evidence from gene and protein levels that dehydration affects cytokine production and extracellular matrix components (ECM) in vocal fold, demonstrating the vocal fold tissue biomechanical behavior after dehydration and loss of HA, and offering a combination application of MRA and ultrasound imaging to study vascular geometry and hemodynamics of the blood supply to the vocal fold region.</p>

<p>A multitude of neurologic diseases are increasing in patients that both diminish quality and quantity of life. My dissertation research focused on unraveling the blood-brain barrier’s alterations (BBB), primarily in lung cancer brain metastases, the most common brain metastasis in patients. We optimized a reliable and reproducible mouse model for creating brain metastases using patient derived brain seeking cells of non-small lung cancer (NSCLC) using ultrasound-guided intracardiac injection. I then evaluated brain tissue with qualitative and quantitative immunofluorescence for individual components of the BBB. Using this experimental method, I was able to identify the specific shift of each BBB component over time in NSCLC brain metastases. I then used human brain metastases specimens to demonstrate the clinical relevance of my findings. These results show distinct alterations in the BBB, which have the potential for targeting therapeutic delivery to extend patient survival. I was also able to characterize a novel epithelial-mesenchymal (EMT) phenotype in vertebral metastases of NSCLC in our model, with features similar to those seen in human patients. Most recently, I analyzed patterns of paracellular permeability associated with each BBB component of NSCLC brain metastases which may provide direct passageways for therapeutic delivery. Altogether, this research offered foundational evidence for the future development of targeted novel therapeutics, including nanoparticles. Outside of the brain metastases field, we used an experimental framework to successfully characterize the BBB alterations in a traumatic brain injury model (bTBI). These findings provided the first description of this unique pathology and the framework for developing therapeutics in other neurologic diseases. Although my research work has focused on animal models of disease, future directions based on my research work include the developing a novel 3D BBB-on-chip device to enable high throughput novel therapeutic delivery through the BBB. Long-term, identifying targetable alterations in the restrictive BBB using <i>in vitro</i> and <i>in vivo</i> models provides a potential conduit for effective prevention and treatment of a myriad of neurologic diseases to prolong patient survival and quality of life.</p>