The Mouse Auditory Testing (MAT) Core facility assists the Principle Investigators of the NIDCD and their collaborators with auditory and vestibular function testing in mice. Two physiological measures of auditory function are employed at the MAT Core: the auditory brainstem response (ABR) and distortion-product otoacoustic emissions (DPOAEs). The ABR is an evoked potential that can be used to estimate hearing thresholds. DPOAEs are soft sounds that are recorded in the ear canal using a small microphone. DPOAEs can be used to screen for hearing loss and to evaluate inner ear function; specifically, the presence of DPOAEs indicates normal function of outer hair cells in the inner ear. The facility also assists with noise exposure protocols. Development of a vestibular sensory evoked potentials (VsEPs) system was completed this year. VsEPs are recorded by placing electrodes on the scalp and recording the electrical potentials generated by the vestibular nervous system in response to linear movements of the head. Dr. Fitzgerald and Dr. Talah Wafa (Post-Doctoral Fellow) collaborated with Dr. Sherri Jones, Dr. Timothy Jones, and Dr. Sarath Vijayakumar of the University of Nebraska-Lincoln and with Connor Schultz (Student), John Kakareka (Electronics Engineer), and Thomas Pohida (Staff Scientist) from the Signal Processing and Instrumentation Section (SPIS) of the Computational Bioscience and Engineering Lab (CBEL) in the Center for Information Technology (CIT) at the NIH. Elizabeth Wilson Bernhard (Biologist, Laboratory of Molecular Genetics, NIDCD) assisted with pilot data collection. Dr. Fitzgerald trained 10 NIDCD investigators in auditory function testing and two NIDCD investigators in vestibular function testing. Five investigators completed auditory function testing independently but received support from the MAT Core. Dr. Fitzgerald trained two investigators from other NIH Institutes (NIMH, NIA) and one investigator from outside the NIH (School of Medicine, University of Maryland-Baltimore) in auditory testing and data analyses. Dr. Fitzgerald began training two investigators from the Blast-Induced Neurotrauma Branch at Walter Reed Army Institute of Research in vestibular function testing and data analyses. Dr. Fitzgerald collaborated on and/or supported 29 projects conducted in nine NIDCD labs, including a collaboration between the Kelley lab at NIDCD and the Blast-Induced Neurotrauma Branch at Walter Reed Army Institute of Research. Dr. Fitzgerald collaborated on two projects from labs in other NIH institutes (NIA, NIMH). Dr. Fitzgerald was a co-author on two manuscripts published this past year. Information on collaborations with specific laboratories is listed below. Inner Ear Gene Therapy Program (PI: Wade Chien, M.D.) Dr. Fitzgerald collaborated on and/or supported seven projects investigating the use of gene therapy to remediate hearing loss. Dr. Fitzgerald assisted with preparation of one published manuscript. Dr. Fitzgerald trained Dr. Hong Jun Wang (Staff Scientist) in auditory function testing and data analyses and provided support to Kevin Isgrig (Biologist). Section on Sensory Cell Biology (PI: Lisa Cunningham, Ph.D.) Dr. Fitzgerald provided support to Katie Spielbauer (MRSP Fellow) and Dr. Katharine Fernandez (Staff Scientist) for two projects examining the prevention of Cisplatin ototoxicity. Laboratory of Molecular Genetics (PI: Thomas Friedman, Ph.D.) Dr. Fitzgerald collaborated on six projects examining auditory function in various mutant mouse strains, including projects with Dr. Inna Belyantseva (Staff Scientist), Dr. Jonathan Bird (Visiting Post-Doctoral Fellow), Dr. Melanie Barzik (Staff Scientist), Dr. Ayesha Imtiaz (Post-Doctoral Fellow), and Dr. Risa Tona (Post-Doctoral Fellow). Dr. Fitzgerald assisted Dr. Robert Morell (Director, Genomics and Computational Biology Core) with three projects investigating auditory function in mutant mice. Dr. Fitzgerald assisted with set-up and calibration of noise exposure experiments. Dr. Fitzgerald trained Randall Harley (Post-Bac IRTA) and Connor Hill (Post-Bac IRTA) and provided continued training and/or support to Rabia Faridi (Pre-Doctoral Visiting Fellow), Risa Tona (Post-Doctoral Fellow), Kerianne Richards (Bioinformatist, Genomics and Computational Biology Core) and Elizabeth Wilson Bernhard (Biologist). Dr. Fitzgerald and Elizabeth Wilson Bernhard continued work on a survey of auditory sensitivity with age in the Friedman lab C57Bl6J and B6.CAST-Cdh23 Ahl+/Kjn mice. Dr. Fitzgerald assisted with preparation of one published manuscript. Section on Molecular Biology and Genetics (PI: Andrew Griffith, M.D., Ph.D.) Dr. Fitzgerald continued training Danielle Harrow (Biologist) in auditory testing and data analyses and collaborated on and/or supported her two projects examining auditory function in mutant mice. Section on Structural Cell Biology (PI: Bechara Kachar, Ph.D.) Dr. Fitzgerald continued training Miloslav Sedlacek (Post-Doctoral Fellow) in auditory testing and data analyses and collaborated and/or supported his three projects examining auditory function in mutant mice. Laboratory of Cochlear Development (PI: Matthew Kelley, Ph.D.) Dr. Fitzgerald continued training Dr. Elizabeth Driver (Staff Scientist) in auditory testing and data analyses for her project investigating a mouse model of riboflavin transporter deficiency syndrome. Dr. Fitzgerald began training Rodrigo Urioste (Student) and Yan Su in vestibular function testing for a collaboration between the Kelley lab and the Blast-Induced Neurotrauma Branch at Walter Reed Army Institute of Research on the effects of blast exposure on auditory and vestibular function in mice. Integrative Theraputics Program (PI: Nicole Schmitt, M.D.) Dr. Fitzgerald supported a study of the effects of immunotherapy on Cisplatin otoxicity in mice conducted in collaboration with Dr. Lisa Cunningham's lab. Section on Neuronal Circuitry (PI: Catherine Weisz, Ph.D.) Dr. Fitzgerald continued work on a new, custom system for a future project on DPOAE suppression in mice. Section on Sensory Cell Regeneration and Development (PI: Doris Wu, Ph.D.) Dr. Fitzgerald continued training Dr. Kazuya Ono (Post-Doctoral Fellow) for a project examining auditory function in mutant mice. Dr. Fitzgerald and Dr. Talah Wafa trained Dr. Ono in vestibular function testing and data analyses for a collaboration on vestibular and auditory function in mutant mice. Laboratory of Molecular Gerontology, NIA (PI: Vilhelm Bohr, M.D., Ph.D.) Dr. Fitzgerald trained M. Nazir Okur (Post-Doctoral Fellow) in auditory function testing and data analyses for a project on a mouse model of Cockayne Syndrome (CS) conducted in collaboration with the Kelley Lab. Unit on Neural Circuits and Adaptive Behaviors, NIMH (PI: Kaun Hong Wang, Ph.D.) Dr. Fitzgerald trained Fhatarah Zinnamon (NIMH-UCL GPP Program IRTA Fellow) in auditory function testing and data analyses for her project examining Df1/+ mice. In July 2017, the MAT Core participated in the annual Earssentials workshop, a week-long course designed to expose new trainees to auditory research at the NIDCD through lectures and laboratory exercises. Twelve students participated in a laboratory training exercise on auditory testing in mice given by Dr. Fitzgerald, Elizabeth Wilson Bernhard, and Katharine Fernandez.

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6
Fiscal Year
2017
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Deafness & Other Communication Disorders
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Nakanishi, Hiroshi; Kurima, Kiyoto; Pan, Bifeng et al. (2018) Tmc2 expression partially restores auditory function in a mouse model of DFNB7/B11 deafness caused by loss of Tmc1 function. Sci Rep 8:12125
Imtiaz, Ayesha; Belyantseva, Inna A; Beirl, Alisha J et al. (2018) CDC14A phosphatase is essential for hearing and male fertility in mouse and human. Hum Mol Genet 27:780-798
Bird, Jonathan E; Barzik, Melanie; Drummond, Meghan C et al. (2017) Harnessing molecular motors for nanoscale pulldown in live cells. Mol Biol Cell 28:463-475
Breglio, Andrew M; Rusheen, Aaron E; Shide, Eric D et al. (2017) Cisplatin is retained in the cochlea indefinitely following chemotherapy. Nat Commun 8:1654
Tran, Linda; Allen, Clint T; Xiao, Roy et al. (2017) Cisplatin Alters Antitumor Immunity and Synergizes with PD-1/PD-L1 Inhibition in Head and Neck Squamous Cell Carcinoma. Cancer Immunol Res 5:1141-1151
Isgrig, Kevin; Shteamer, Jack W; Belyantseva, Inna A et al. (2017) Gene Therapy Restores Balance and Auditory Functions in a Mouse Model of Usher Syndrome. Mol Ther 25:780-791
Nishio, Ayako; Ito, Taku; Cheng, Hui et al. (2016) Slc26a4 expression prevents fluctuation of hearing in a mouse model of large vestibular aqueduct syndrome. Neuroscience 329:74-82
Chien, Wade W; McDougald, Devin S; Roy, Soumen et al. (2015) Cochlear gene transfer mediated by adeno-associated virus: Comparison of two surgical approaches. Laryngoscope :
Morozko, Eva L; Nishio, Ayako; Ingham, Neil J et al. (2015) ILDR1 null mice, a model of human deafness DFNB42, show structural aberrations of tricellular tight junctions and degeneration of auditory hair cells. Hum Mol Genet 24:609-24
Chien, Wade W; Isgrig, Kevin; Roy, Soumen et al. (2015) Gene therapy restores hair cell stereocilia morphology in inner ears of deaf whirler mice. Mol Ther :

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