Multi-Omic and Functional Analyses for Hearing Preservation and Restoration

National Institute On Deafness And Other Communication Disorders

Investigators

Linked publications & trials

Abstract

Our laboratory, situated within the neurotology branch, is dedicated to investigating the coordinated regulation of gene expression across the diverse cell types of the inner ear. Our primary objective is to comprehend the molecular programs governing inner ear development and function, ultimately striving to pioneer new therapies for both genetic and acquired hearing loss. Our collaborative efforts encompass a wide spectrum, ranging from genetics and functional genomics to imaging and hearing/balance physiology. We employ a diverse range of in vitro and in vivo models. In addition to our innovative research pursuits, we also place a strong emphasis on nurturing the next generation of scientists and clinician-scientists. Outlined below are the three key focus areas that drive our work: Cell-Type Specific Molecular Pathways in Inner Ear Development: Our expertise lies in identifying transcription factors and gene regulatory networks pivotal to inner ear development and function. Through this exploration, we unveil novel genes and pathways critical to the restoration of hearing. Sex Differences in Hearing and the Molecular Basis of Acquired Hearing Loss: Our research is geared towards deciphering the fundamental differences in hearing physiology and susceptibility to noise between genders. Our goal is to pave the way for potential therapeutic interventions. Tools for Sharing, Visualizing, and Analyzing Multi-Omic Data: We have developed the gene Expression Analysis Resource (umgear.org), a comprehensive platform for the visualization, analysis, and sharing of multi-omic data. This year marked a significant transition for our laboratory, as we moved from the University of Maryland School of Medicine to the National Institute on Deafness and Other Communication Disorders. Despite the considerable efforts required for this transition, including setting up the new lab, staffing, and adapting and re-establishing animal protocols, we continued to make substantial progress on all three fronts. Cell-Type Specific Molecular Pathways in Inner Ear Development: We made strides in understanding the molecular pathways downstream of RFX in vestibular hair cell development. We highlighted the crucial role of group 1 RFX transcription factors in differentiation and function. Our investigations also unveiled the signaling pathway influenced by IKZF2 in outer hair cell development, shedding light on its involvement in differentiation and maintenance. Notably, our work showcased the presence of four distinct molecular, functional, and spatial populations within otic mesenchyme cells. This research emphasized the significance of this cell type, often understudied despite its abundance during development, and its role in inner ear paracrine signaling. Sex Differences in Hearing Physiology and Prevention of Acquired Hearing Loss: Our studies identified downstream mediators of the estrogen signaling pathway as pivotal for otoprotection in female mice. Moreover, we successfully established Metformin's otoprotective role against noise-induced hearing loss in male mice, with differential outcomes observed in females. Tools for Sharing, Visualization, and Analyzing Multi-Omic Data: We advanced the development of the gEAR portal, reaching over 2000 registered users and 1137 datasets. Collaborating with a user-interface/user-experience group from the University of Maryland College Park, we designed a blueprint to revamp the interface based on user feedback. We introduced analysis and visualization tools, including a projection tool, and made substantial enhancements to the workbench. Through more than ten workshops during the Association for Research in Otolaryngology meetings, we assisted users in mastering the platform. Our commitment to staying current saw us continually update the platform with newly published datasets from the field. These accomplishments underscore our dedication to pioneering advancements in the understanding of inner ear biology, with the ultimate goal of alleviating the burden of hearing loss.