PROJECT SUMMARY/ABSTRACT Overall Plan for the Translational Hearing Center This Center of Biomedical Research Excellence (COBRE) application is to establish the Translational Hearing Center, administered by centrally-located Creighton University, with Boys Town National Research Hospital (BTNRH) and the University of Nebraska Medical Center (UNMC), as institutional partners. Our overall goal is to build a critical mass of academic translational researchers developing therapeutic interventions to preserve or restore hearing and vestibular function from a wide range of etiologies that cause hearing loss and vestibular deficits. Hearing loss in infants and children results in delayed acquisition of listening and spoken language skills critical for academic achievement and maximal career trajectories of affected individuals. In the aging population, hearing loss and vestibular deficits without appropriate rehabilitation accelerates aging and cognitive decline. Aim 1: Develop the infrastructure and expertise base for translational auditory and vestibular research. COBRE funding will enable an Administrative Core within the Center to provide a unique, transformational research environment for junior investigators to translate their basic science discoveries into therapeutic strategies that preserve or restore hearing and vestibular function. This will establish a broader nonclinical research program. The Administrative Core will coordinate interactions between project leaders with their Mentors, and an External Advisory Committee. The Administrative Core will develop a Drug Discovery and Delivery Core that will coordinate necessary drug screen assays and production of derivatives of lead compounds and their delivery to the inner ear and associated central neural pathways, as well as an Auditory Vestibular Technology Core to validate the efficacy of lead candidate ototherapeutics hits. Aim 2: Build a critical mass of funded investigators leading translational auditory and vestibular research. We will examine both peripheral and central mechanisms of hearing loss and vestibular dysfunction, and identify pharmacotherapeutic strategies preserve or restore hearing and vestibular function, with multiple levels of research funding for investigators. We also have an outstanding Mentoring Plan for project leaders, complementing their expertise with senior investigations as Internal Mentors and biostatistical support, as well as outside investigators with translational and clinical expertise as External Mentors. Additional mentoring is provided by Research Core staff, grantsmanship classes and Mock Study Sections of proposals prior to review. Evaluations of research progress, and all other Center activities, are also key to optimize Center success. The Center will also benefit from the burgeoning translational research environment in Omaha, Nebraska. Future plans call for continued expansion of the Center to include submission of Investigational New Drug applications, safety and efficacy studies and clinical trials in partnership with patient populations served by Creighton University’s academic medical center, Catholic Health Initiatives (CHI) Health system, BTNRH and UNMC.

PROJECT NARRATIVE Overall: Translational Hearing Center The Translational Hearing Center will build a broad, critical mass of academic translational researchers to develop therapeutics that preserve or restore sensory function in genomic, medical and environmental settings known to cause hearing loss or vestibular deficits. This will accelerate translation of candidate therapeutics towards clinical trials in an increasingly wider range of etiologies that predispose individuals to a higher risk of hearing loss or vestibular deficits.