Dr. Alexander Hillel is a faculty member in the Department of Otolaryngology-Head & Neck Surgery at the Johns Hopkins School of Medicine where his clinical practice is dedicated to the medical and surgical management of laryngotracheal stenosis. With the support of a R01 Research Project Grant, he seeks to better understand mechanisms of laryngotracheal stenosis (LTS) and apply regenerative medicine techniques to its treatment. Specifically, Dr. Hillel will be focusing on the mTOR mechanism and targeted inhibition of mTOR as a novel approach to treating LTS in vitro on human LTS-scar fibroblasts and in vivo in a validated mouse model of LTS. This proposal will study the mechanism of how mTOR suppression works on the pathologic T-cell and fibroblast subsets that are critical to the development of iLTS. It also will study how the dysregulated T-cell subsets interact with healthy and diseased fibroblasts to understand the pathogenesis of this devastating disease. Finally, the proposal will test a novel drug eluting stent to deliver mTOR suppression directly to the site of disease in the larynx and trachea to target diseased T-cells and fibroblasts without side effects of systemic mTOR inhibition. Through a combination of in vitro and in vivo modeling, participation from patients with iLTS, and a novel biomaterials approach, the investigator team is uniquely poised to transform our understanding and treatment of LTS. Preclinical validation of mTOR inhibition as a treatment for LTS is a critical step prior to translation to human studies.
Laryngotracheal stenosis (obstructing scar in the larynx and trachea) occurs in patients after long-term breathing tube placement and can result in communication disability and high mortality rates due to the obstructed airway. This proposal will investigate the mechanism of how mTOR suppression works on the pathologic T-cell and fibroblast subsets that are critical to the development of iLTS. Finally, the proposal will test a novel drug eluting stent to deliver mTOR suppression directly to the site of disease in the larynx and trachea to target diseased T- cells and fibroblasts without side effects of systemic mTOR inhibition. !
