Immune Cell Modulation in Laryngotrachael Fibrosis

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 DESCRIPTION (provided by applicant): Dr. Alexander Hillel is a junior 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 voice and airway disorders. With the support of a Mentored Career Development Award, Dr. Hillel seeks to better understand the inflammatory mechanisms of laryngotracheal fibrosis (LTF) and apply regenerative medicine techniques to its treatment. Specifically, Dr. Hillel will be focusing on mammalian target of rapamycin (mTOR), which has been shown to activate the same type of T cells and macrophages in pulmonary fibrosis that has been observed in early models of LTF. Ultimately, he plans to develop a drug-eluting stent to target the immune mechanisms. Aim 1 will characterize the inflammatory response to mechanical injury in the mouse trachea and then determine the role of mTOR in regulating macrophages and T-lymphocytes that precede LTF in a novel in vivo in situ mouse model. Aim 2 will characterize the role of macrophages, T-lymphocytes, and their inflammatory cytokines in patient with and patients at risk for developing LTF. Finally, Aim 2 will focus on identifying an ideal bioabsorbable polymer to engineer a drug-eluting airway stent targeting mechanisms identified in earlier aims. During the course of this proposal, Dr. Hillel will enhance his research knowledge and skills with coursework in immunology, biostatistics, and ethical research, receive directed mentorship by an interdisciplinary team of experienced researchers, and be immersed in the interdisciplinary research and clinical environments of the Johns Hopkins School of Medicine, Johns Hopkins Bloomberg School of Public Health, and the Laryngeal Research Group at The Wisconsin Institute of Medical Research in Madison, Wisconsin. This Career Development Award will provide Dr. Hillel with the resources that he needs to become an independent investigator and future leader in voice science research.