The Mouse Auditory Testing Core (MATC) Facility assists the Principle Investigators of the NIDCD and their collaborators with auditory testing in mice, including experimental design, data collection and analyses, and preparation of auditory test data for presentation or publication. Dr. Fitzgerald trains investigators in auditory testing techniques. The facility also assists with protocols that require noise exposure. Two physiological measures of auditory function are employed at the MATC: 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. The ABR is measured by placing electrodes on the scalp and recording the potentials generated by the auditory nervous system when a sound is repeatedly presented to the ear. DPOAEs are soft sounds that are recorded in the ear canal and can be used to screen for hearing loss and to evaluate inner ear (cochlear) function. The presence of DPOAEs indicates normal function of outer hair cells in the inner ear. DPOAEs are measured by placing a small probe containing two speakers and a microphone in the opening of the ear canal. Two tones are played simultaneously to the ear, and the DPOAEs produced by the ear are recorded by the microphone. In the fourth year of operation, Dr. Fitzgerald trained 10 new investigators from the NIDCD and one investigator from the NEI in DPOAE and ABR testing and interpretation. An additional 10 investigators from the NIDCD continued training from the previous year or received on-going support from the MATC. Dr. Fitzgerald collaborated on 22 projects conducted in seven NIDCD labs and on one project for a lab in the NEI. Dr. Fitzgerald assisted with planning auditory test protocols, collection of DPOAE and ABR data, and analysis of auditory test data. Dr. Fitzgerald provided ongoing support such as equipment calibration and maintenance and troubleshooting as necessary. Dr. Fitzgerald was a co-author on two manuscripts published this past year and on one paper currently in press. Information on collaborations with specific laboratories is listed below. Neurotology Program (NIDCD), PI: Wade Chien, M.D. Dr. Fitzgerald collaborated on six projects investigating the use of gene therapy to remediate hearing loss. Dr. Fitzgerald assisted with manuscript preparation for two additional projects; both were accepted for publication in the past year. Dr. Fitzgerald trained Joan Guitart (Post-Bac IRTA), Dr. Jasmine Saleh (Post-Doctoral IRTA Fellow), and Jack Shteamer (Pre-Doctoral IRTA) in DPOAE and ABR testing and interpretation. Assistant investigators Kevin Isgrig (Biologist) and Dr. Bovey Zhu (Special Volunteer) received continued training and support. Section on Sensory Cell Biology (NIDCD), PI: Lisa Cunningham, Ph.D. Dr. Fitzgerald collaborated on two projects examining the use of moderate noise exposure to reduce the hearing loss caused by the ototoxic drug cisplatin. Dr. Fitzgerald also assisted with set-up and calibration of noise exposures for these experiments. Dr. Fitzgerald consulted with the Cunningham Lab and Audiology Unit regarding pilot projects examining ABR wave amplitudes in humans. Aaron Rusheen (Post-Bac IRTA) and Dr. Soymen Roy (Visiting Post-Doctoral Fellow) received continued training and support. Laboratory of Molecular Genetics (NIDCD), PI: Thomas Friedman, Ph.D. Dr. Fitzgerald collaborated on five projects in the Friedman lab examining auditory function in various mutant mouse strains, including projects with Dr. Inna Belyantseva (Staff Scientist), Dr. Jonathan Bird (Visiting Post-Doctoral Fellow), Dr. Meghan Drummond (Post-Doctoral IRTA Fellow), and Dr. Ayesha Imtiaz (Post-Doctoral Fellow). Dr. Fitzgerald also assisted Dr. Robert Morell (Director, Genomics and Computational Biology Core) with three projects investigating auditory function in three strains of mutant mice. Dr. Fitzgerald assisted with set-up and calibration of noise exposure experiments for Drs. Drummond and Morell. Dr. Fitzgerald trained Dr. Drummond, Joseph Duda (Student IRTA), Dr. Imtiaz, Alexis Oguh (Post-Bac IRTA), Arik Shams (Post-Bac IRTA), Daniel Sutton (Post-Bac IRTA), Elizabeth Thomason (Post-Bac IRTA), and Elizabeth Wilson (Biologist) in DPOAE and ABR testing and interpretation. Dr. Fitzgerald trained Dr. Drummond, Alexis Oguh, and Elizabeth Thomason in calibration and administration of noise exposure protocols. Dr. Fitzgerald and Elizabeth Wilson undertook a survey of auditory sensitivity with age in the Friedman lab C57BL/6J mouse colony in late September 2014. This project is ongoing. Section on Molecular Biology and Genetics (NIDCD), PI: Andrew Griffith, M.D., Ph.D. Dr. Fitzgerald provided continued support to Dr. Ayako Nishio (Visiting Post-Doctoral Fellow) on two projects investigating Slc26A4 mutant mice and to Dr. Kiyoto Kurima (Staff Scientist) on a project investigating Tmc1 and Tmc2 mutant mice. Laboratory of Auditory Restoration and Development (NIDCD), PI: Michael Hoa, M.D. Dr. Fitzgerald collaborated on a project investigating auditory and vestibular function in Sna1 mutant mice. Dr. Fitzgerald trained Dr. Rafal Olszewski (Biologist) in DPOAE and ABR testing and interpretation. Laboratory of Cochlear Development (NIDCD), PI: Matthew Kelley, Ph.D. Dr. Fitzgerald collaborated with Dr. Elizabeth Driver (Staff Scientist) on a project investigating a novel transport protein associated with human deafness. Dr. Fitzgerald consulted on experimental design and equipment setup 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. Dr. Fitzgerald trained Stephen McInturff (Post-Bac IRTA) in DPOAE and ABR testing and interpretation. Laboratory of Molecular Biology (NIDCD), PI: Doris Wu, Ph.D. Dr. Fitzgerald collaborated with Dr. Kazuya Ono (Visiting Post-Doctoral Fellow) on a project investigating auditory function in Raldh3 mutant mice. Dr. Fitzgerald trained Dr. Ono in DPOAE and ABR testing and interpretation. Neurobiology, Neurodegeneration, and Repair Laboratory (NEI), PI: Tiansen Li, Ph.D. Dr. Fitzgerald collaborated with Dr. Vetrival Sengottuvel (Visiting Post-doctoral Fellow) on a project investigating a novel photoreceptor protein and how the loss of this protein impacted auditory function. Dr. Fitzgerald trained Dr. Sengottuvel in DPOAE and ABR testing and interpretation. In July 2015, the MATC participated in the second annual Earssentials, a week-long course designed to expose new trainees to auditory research at the NIDCD through lectures and laboratory exercises. 16 students from both the NIDCD and outside the NIH participated in a laboratory training exercise on DPOAE and ABR measures in mice given by Dr. Fitzgerald and Elizabeth Wilson (Biologist, Laboratory of Molecular Genetics). Assembly of a vestibular sensory evoked potentials (VsEPs) system began in the summer of 2013 and is nearing completion. VsEPs are recorded by placing electrodes on the scalp, similar to an ABR, and recording the electrical potentials generated by the vestibular nervous system in response to linear movements of the head. Dr. Fitzgerald collaborated with Jessica Crouch (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) on a custom-made component that will convert acceleration to jerk for calibration of the stimulus.

Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Deafness & Other Communication Disorders
Department
Type
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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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