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Carmen C. Brewer, Ph.D., Chief Research Audiologist
This video explores how Carmen Brewer, Ph.D., and Kelly King, Au.D., Ph.D., NIDCD research audiologists at the NIH Clinical Center's Audiology Unit, study and help to treat young patients with a rare disease.
The Audiology Unit functions as both a research and clinical laboratory. Within these broad areas, we develop and conduct audiology-specific research studies; collaborate with intramural investigators in the development and implementation of protocols that include assessment of the auditory and vestibular systems; provide audiology services to support NIH Clinical Center patient needs; and provide clinical and research training and mentoring.
Currently, our research can be divided into four areas: 1) natural history of disorders affecting the auditory and vestibular systems; 2) clinical monitoring of potentially ototoxic therapeutic and diagnostic interventions; 3) auditory processing skills; and 4) investigation of normal variation in auditory and vestibular function.
Christopher Zalewski, Ph.D., assesses balance function using dynamic computerized platform posturography.
Our natural history studies are directed toward identifying and defining distinctive auditory and vestibular phenotypes, understanding their pathogenesis, and correlating these phenotypes with underlying molecular genotypes. Many of our studies are multidisciplinary and part of NICHD, NEI, NCI, NIAMS, NINDS, and NHGRI clinical research protocols on a variety of chromosomal and syndromic disorders affecting hearing and balance. We use a comprehensive battery of auditory and vestibular measures that includes otoacoustic emissions, wideband acoustic reflectance, assessment of auditory processing, auditory and vestibular evoked potentials, videonystagmography, rotary vestibular testing, and computerized dynamic platform posturography. Examples of ongoing research include examining auditory and/or vestibular manifestations of neurofibromatosis type 2 (NF2), Usher syndrome, enlarged vestibular aqueducts (EVA), Niemann-Pick type C (NPC), xeroderma pigmentosum (XP) and Moebius syndrome.
Vestibular function is assessed using rotary vestibular testing.
Videonystagmography is used to assess vestibular function.
Our clinical monitoring studies focus on hearing loss and other aspects of auditory function associated with ototoxins and clinical noise (e.g., MRI, TMS). They are conducted with the aim of early identification of hearing loss or other subtle damage to the ear as well as long term monitoring of patients treated with potentially ototoxic drugs such as aminoglycoside antibiotics, cisplatinum, experimental therapies, and as the result of radiation therapy to the brain. One investigation in which the NIDCD Audiology Unit has been involved combines a natural history study and clinical monitoring of hearing function during an experimental treatment of persons with Niemann-Pick type C1, a rare, progressive, and fatal disease.
Audiology students prepare to test auditory processing skills of twins.
We conduct studies of auditory processing (AP) that focus on heritability of these skills in the general population and manifestation of these abilities in certain patient groups. In conjunction with the NIDCD’s Laboratory of Molecular Genetics we have shown that dichotic listening, or the ability to listen to and understand different speech signals presented to each ear at the same time, is inherited (Morell, et al. 2007). We have recently expanded our findings to show that there is heritability for AP of non-speech signals as well (Brewer et al., in press). This will enable us to understand better the underpinnings of AP. To date, much of this work was conducted at the Annual Twins Days Festival in Twinsburg, Ohio, where our team of researchers evaluated the AP skills of volunteer twin pairs. We are also examining AP skills in groups of patients with syndromes that may affect AP such as OCA, NF1 and WAGR syndrome.
We also investigate normative aspects of auditory and vestibular function in healthy volunteers. Our goals are to better understand normal function, determine ranges of normal variability, and identify the best and novel methods for evaluating the auditory and vestibular systems. We are currently examining the feasibility of methods to evaluate otolith organs of the balance system using rotary vestibular testing and measures of eye muscles associated with the vestibular system (ocular vestibular evoked myogenic potentials or oVEMP). In a separate study, we are evaluating stability of auditory nerve responses to sound over repeated measures with the goal of using this as a monitoring tool for subtle changes in auditory function that are not detected by a standard audiogram.
Student Mentorship Programs
The Audiology Unit offers clinical and research mentorship opportunities. A placement at the NIH is best suited for a person who is interested in the medical or genetic aspects of audiology, or both, as well as those who may have an interest in eventually pursuing a Ph.D. or a career in research. Please see How to Apply for Clinical and Research Mentorship Opportunities in the NIDCD Audiology Unit for application instructions.
Dr. Brewer provides instruction to a student as a patient is prepared for auditory evoked potential testing.
Clinical mentorship opportunities are available to Doctor of Audiology (Au.D) or Ph.D. students only. These are offered year round on a semester or quarterly basis, in conjunction with the student’s academic program. We see adult and pediatric patients with a wide range of rare diseases and syndromes, patients on potentially ototoxic and/or investigational treatments, as well as healthy volunteers. Students are given the opportunity to work closely with NIDCD otolaryngologists, other physicians, and various other medical professionals. In addition, students may participate in weekly lab meetings and periodic journal clubs, attend NIDCD seminar lecture series, and have opportunities to attend NIH-sponsored lectures from world-renowned scientists and physicians.
Semester, summer, and project-based research opportunities are available to high school, undergraduate, and graduate students.
Summer research program: This opportunity is available to high school, undergraduate, and graduate students and is subject to availability from year-to-year depending on research needs. Projects include retrospective review and data analysis, and preparation for data acquisition for upcoming projects. Those interested in participating in the NIH summer student research program must apply though www.training.nih.gov/programs/sip. We give preference to those pursuing a career in audiology or hearing science. Summer students participate in lab meetings and journal club. Those completing a project with data analysis are expected to present at least one status report in our lab meetings and to prepare a poster for presentation at the NIH Summer Research Festival.
Case discussion with audiology students.
Semester- and project-based research: This opportunity is available to doctoral students in audiology/hearing science who are seeking to complete a research project as part of their academic requirements for the doctoral degree. We primarily offer opportunities for retrospective review and data analysis, and mentor the student through literature review, design of experimental questions, database management, statistical analysis, and research product development. The research product may be a capstone project, thesis, dissertation, research poster, and/or a manuscript submitted for publication. Independent work is expected. Approval by your academic advisor is required before we will agree to a research rotation. You will be required to lead at least one journal club, and make at least one presentation during lab meeting.
Selected Student Projects
- Megan Brenda, B.A. postbaccalaureate IRTA, undergraduate degree in psychology and speech and hearing sciences, University of Mexico. Brendal M, King K, Zalewski C, Finucane B, Introne W, Brewer C, Smith A. Auditory phenotype of Smith-Magenis syndrome. Poster presented at American Society of Human Genetics, Baltimore, October 2015.
- Hope Schmid, undergraduate communication sciences and disorders major, The Pennsylvania State University, University Park, PA. Schmid H, King K, Zalewski C, Giri N, Alter B, Kim HJ, Brewer C. The power of reflectance: identifying middle ear abnormalities in Fanconi Anemia. Poster presented at the NIH Summer Student Poster Series, August 2015.
- Spencer Lindsey, M.D., otolaryngology resident, Georgetown University, Washington DC. Lindsey S, Brewer C, Stakhovskaya O, Kim HJ, Zalewski C, King K, Marshall J, Gunay-Aygun M. Auditory and otologic phenotypic manifestations of Alstrom syndrome. Poster presented at the Combined Otolaryngology Spring Meeting, Boston, April 2015.
- Olga Stakhovskaya, M.D., Ph.D., doctoral student in audiology (Au.D.), University of Maryland, College Park, MD. Stakhovskaya O, King KA, Zalewski CK, Warren K, Adams D, Brewer C. Long-term stability and accuracy of otoacoustic emissions in pediatric ototoxicity monitoring. Poster presented American Auditory Society Scientific and Technical Meeting, Scottsdale, AZ, March 2015 *Travel award winner.
- D. Rudyard Nast, B.S., doctoral student in audiology (Au.D.), University of Florida, Gainsville, FL. Nast DR, Zalewski C, King K, Manoli I, Sloan J, Venditti C, Brewer C. Auditory Phenotype of patients with isolated methylmelonic acidemia. Poster presented American Auditory Society Scientific and Technical Meeting, Scottsdale, AZ, March 2014. *Travel award winner.
- Talah Wafa, Au.D., doctoral student in audiology and hearing science, Gallaudet University, Washington DC. Wafa T, Shultz J, Zalewski C, King K, Turiff A, Griffith A, Friedman T, Zein W, Brewer C. Comprehensive vestibular assessment in Usher syndrome: Genotype/phenotype correlations. Poster presented at NIH Research Festival, Bethesda, October 2013.
- Carmen C. Brewer, Ph.D Chief Research Audiologist +1 301 496 5294 (Send e-mail (link sends e-mail))
- Kelly King, Au.D., Ph.D. +1 301 496 5036 (Intramural, Audiology Unit) (Send e-mail (link sends e-mail))
- Talah Wafa, Au.D. Doctoral fellow +1 301 402 2154 (Send e-mail (link sends e-mail))
- Christopher Zalewski, Ph.D. Research Audiologist +1 301 496 5145 (Send e-mail (link sends e-mail))
- Zalewski CK, Chien WW, King KA, Muskett JA, Baron RE, Butman JA, Griffith AJ, Brewer CC. Vestibular dysfunction in patients with enlarged vestibular aqueduct. Otolaryngol Head Neck Surg. 2015 Aug 153(2):257-62.
- Lawrence MG, Leiding JW, Lyons JJ, Hsu AP, Nelson CC, Jones N, Fitzgerald A, Chien WW, Workman L, Platts-Mills TA, Brewer C, Gafni RI, Stone KD, Milner JD, Holland SM. GATA3 haploinsufficiency does not block allergic sensitization or atopic disease. J Allergy Clin Immunol. 2015 Aug 15.
- Muskett J, Chattaraj P, Heneghan JF, Reimold FR, Shmukler BE, Brewer CC, King KA, Zalewski CK, Shawker TH, Butman JA, Kenna MA, Chien WW, Alper SL, Griffith AJ. Atypical patterns of segregation of familial enlargement of the vestibular aqueduct. Laryngoscope. 2015 Oct 20. Doe: 10.1002/lary.25737. [Epub ahead of print] PubMed PMID 26485571
- Raza M, Mattera R, Morell R, Sainz E, Rahn R, Gutierrez J, Paris E, Root J Solomon B, Brewer C, Basra MA, Khan S, Riazuddin S, Braun A, Bonfacino JS, Drayna D. Association between rare variants in AP4E1, a component of intracellular trafficking and persistent stuttering. Am J Human Genetics. 20152015 Nov 5;97(5):715-25. doi: 10.1016/j.ajhg.2015.10.007. PubMed PMID: 26544806.
- Brewer CC, Zalewski C, King K, Zobay O, Riley A, Ferguson M, Bird J, McCabe M, Hood L, Drayna D, Griffith A, Morell R, Friedman TB, Moore DR. Heritability of non-speech auditory processing skills. European J. of Human Genetics. In press.
- King KA, Gordon-Salant S, Yanjanin N, Zalewski C, Houser A, Porter FD, Brewer CC. Auditory phenotype of Niemann-Pick disease, type C1. Ear Hear. 2014 Jan-Feb;35(1):110-7.
- Chien WW, Leiding JW, Hsu AP, Zalewski C, King K, Holland SM, Brewer C. Auditory and vestibular phenotypes associated with GATA3 mutation. Otol Neurotol. 2014 Apr;35(4):577-81.
- Olivier KN, Shaw PA, Glaser TS, Bhattacharyya D, Fleshner M, Brewer CC, Zalewski CK, Folio LR, Siegelman JR, Shallom S, Park IK, Sampaio EP, Zelazny AM, Holland SM, Prevots DR. Inhaled amikacin for treatment of refractory pulmonary nontuberculous mycobacterial disease. Ann Am Thorac Soc. 2014 Jan;11(1):30-5.
- Holliday MA, Kim HJ, Zalewski CK, Wafa T, Dewan R, King KA, Brewer CC, Butman JA, Asthagiri AR. Audiovestibular characteristics of small cochleovestibular schwannomas in neurofibromatosis type 2. Otolaryngol Head Neck Surg. 2014 Apr 8;151(1):117-124.
- King KA, Gordon-Salant S, Pawlowski KS, Taylor AM, Griffith AJ, Houser A, Kurima K, Wassif CA, Wright CG, Porter FD, Repa J, Brewer CC. Hearing loss is an early consequence of Npc1 gene deletion in the mouse model of Niemann-Pick disease, type C. J Assoc Res Otolaryngol. 2014 Aug;15(4):529-41.
- Totochny M, Tamura D, Pantell M, Zalewski C, Bradford P, Merchant S, Nadol J, Khan S, Schiffmann R, Pierson T, Wiggs E, Griffith A, DiGiovanna J, Kraemer K, Brewer C. Auditory analysis of xeroderma pigmentosum, 1971-2012: Hearing function, acute sun sensitivity and DNA repair complementation group predict neurologic degeneration. Brain. 2013 Jan;136(Pt 1):194-208. doi: 10.1093/brain/aws317 PMID: 23365097.
- Kim HJ, Hagan M, Butman JA, Baggenstos M, Brewer C, Zalewski C, Linehan WM, Lonser RR.Surgical resection of endolymphatic sac tumors in von Hippel-Lindau disease: findings, results, and indications. Laryngoscope. 2013 Feb;123(2):477-83.
- Viana L, Seyyedi M, Brewer CC, Zalewski C, DiGiovanna J, Tamura D, Totonchy M, Kraemer, KH, Nadol JB Jr. Histopathology of the inner ear in patients with xeroderma pigmentosum and neurological degeneration. Otology and Neurotology. 34:1230-1236, 2013.
- Chattaraj P, Reimold FR, Muskett JA, Shmukler BE, Chien WW, Madeo AC, Pryor SP, Zalewski CK, Butman JA, Brewer CC, Kenna MA, Alper SL, Griffith AJ. Use of SLC26A4 mutation testing for unilateral enlargement of the vestibular aqueduct. JAMA Otolaryngol Head Neck Surg. 2013 Sep;139(9):907-13. PubMed PMID: 24051746.
- Seaman BJ, Guardiani EA,Brewer CC, Zalewski CK, King KA, Rudy S, Van Waes C, Morgan RA, Dudley ME, Yang JC, Rosenberg SA, Kim HJ. Audiovestibular dysfunction associated with adoptive cell immunotherapy for melanoma. Otolaryngol Head Neck Surg. 2012 Oct;147(4):744-9.
- Sibley CH, Plass N, Snow J, Wiggs EA, Brewer CC, King KA, Zalewski C, Kim HJ, Bishop R, Hill S, Paul SM, Kicker P, Phillips Z, Dolan JG, Widemann B, Jayaprakash N, Pucino, Stone DL, Chapelle D, Snyder C, Butman JA, Wesley R, Goldbach-Mansky R. Sustained response and prevention of damage progression in patients with neonatal-onset multisystem inflammatory disease treated with anakinra: a cohort study to determine three- and five-year outcomes.Arthritis Rheum. 2012 Jul;64(7):2375-86.
- Asthagiri AR, Vasquez RA, Butman JA, Wu T, Morgan K, Brewer CC, King K, Zalewski C, Kim HJ, Lonser RR. Mechanisms of hearing loss in neurofibromatosis type 2. PLoS One. 2012;7(9):e46132.
- Rehman A, Gul K, Morell R, Lee K, Ahmed Z, Riazuddin S, Ali R, Shahzad M, Jaleel, A, Andrade P, Khan SN, Khan S, Brewer C, Ahmad W, Leal S, Riazuddin S, Friedman TB. Mutations of GIPC3cause nonsyndromic deafness DFNB72but not DFNB81 that also maps to chromosome 19p,Human Genetics, e pub June 2011.
- Ahmadi N, Brewer C, Zalewski C, King K, Butman J, Plass N., Henderson C, Goldbach-Mansky R, Kim J. Cryopyrin-Associated Periodic Syndromes (CAPS): Otolaryngologic and Audiologic Manifestations, Otolaryngology-Head and Neck Surgery, epub March 31, 2011.
- Guardiani E, Zalewski C, Brewer C, Merideth M, Introne W, SmithACM, Gordon L, Gahl W, Kim HJ. Otologic and Audiologic Manifestations of Hutchinson-Gilford Progeria Syndrome,Laryngoscope, epub Sept 6, 2011.
- Schultz JM, Bhatti R, Madeo A, Turriff A, Muskett A, Zalewski C, King K, Ahmed Z, Riazuddin S, Ahmad N, Hussain Z, Qasim M, Khan S, Meltzer M, Liu X, Munisamy M, Ghosh M, Rehm H, Tsilou E, Griffith A, Zein W, Brewer C, Riazuddin S, Friedman,TB. Allelic hierarchy of CDH23mutations causing nonsyndromic deafness DFNB12 or Usher Syndrome USH1D, Human Genetics, epub Sept 22, 2011.
- Yanjanin N, Velez J, Gropman A, King K, Bianconi S, Conley S, Brewer C, Solomon B, Pavan W, Arcos-Burgos M, Patterson M, and Porter FD. Linear progression, independent of age of onset, in Niemann-Pick disease, type C. Am Journal of Medical Genetics Part B: NeuropsychiatricGenetics, 153B (1): 132-40, 2010.
- King K, Choi BY, Zalewski C, Madeo AC, Manichaikul A, Pryor SP, Ferruggiaro A, Eisenman D, Kim HN, Niparko J, Thomsen J, Butman JA, Griffith AJ, Brewer CC. SLC26A4 genotype, but not cochlear radiologic structure, is correlated with hearing loss in ears with an enlarged vestibular aqueduct. Laryngoscope, 120(2), 384-9, 2010.
- Khan SG, Oh KS, Emmert S, Imoto K, Tamura D, Digiovanna JJ, Shahlavi T, Armstrong N, Baker CC, Neuburg M, Zalewski C, Brewer C, Wiggs E, Schiffmann R, Kraemer KH. XPC initiation codon mutation in xeroderma pigmentosum patients with and without neurological symptoms. DNA Repair (Amst). 8(1): 114-25, 2009.
- Jones JL, Zalewski C, Brewer C, Lucker J, Drayna D. Widespread auditory deficits in tune deafness. Ear Hear. Feb; 30(1):63-72, 2009.
- Choi BY, Stewart A, Madeo A, Pryor S, Lenhard S, Kittles R, Eisenman D, Kim HJ, Niparko J, Thomsen J, Arnos K, Nance W, King K, Zalewski C, Brewer, C., Shawker T, Reynolds J, Butman J, Karniski J, Alper S, Griffith A. Hypo-functional SLC26A4 variants associated with nonsyndromic hearing loss and enlargement of the vestibular aqueduct: genotype-phenotype correlation or coincidental polymorphisms? Hum. Mutat., 2009.
- Jones, JL, Lucker, J, Zalewski C, Brewer, C, and Drayna, D. Phonological Processing In Adults with Deficits in Musical Pitch Recognition. Journal of Communciation Disorders, 42, 2009.
- Johnson L, Morgan R, Dudley M, Cassard L, Yang JC, Hughes MS, Kammula US, Royal RE, Sherry RM, Wunderlich JR, Lee CC, Restifo NP, Schwarz SL, Cogdill AP, Bishop RJ, Kim H, Brewer CC, Rudy SF, Vanwaes C, Davis JL, Mathur A, Ripley RT, Nathan DA, Laurencot CM, Rosenberg SA. Gene therapy with human and mouse t-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood, 114(3) 535-546, 2009.
- Makishima T, King K, Brewer CC, Zalewski CK, Butman J, Bakalov VK, Bondy C, Griffith AJ.Otolaryngologic markers for the early diagnosis of Turner syndrome. Int J Pediatr Otorhinolaryngol, 73(11) 1564-7, 2009.
- Rossi S, Hallett M, Rossini PM, Pascual-Leone A and the Safety of TMS Consensus Group [Brewer, CC, et al.]. Safety, Ethical Considerations, and Application Guidelines for the Use of Transcranial Magnetic Stimulation in Clinical Practice and Research. Clin Neurophysiol, 120(12), 2008-39, 2009.
- Choi BY, Madeo AC, King KA, Zalewski CK, Pryor SP, Muskett JA, Nance WE, Butman JA, Brewer CC, Griffith AJ. Segregation of enlarged vestibular aqueducts in families with non-diagnostic SLC26A4 genotypes. J Med Genet. 46(12):856-61, 2009.
- Merideth M, Gordon L, Claus S, Sachdey V, Smith A, Perry M, Brewer C, Zalewski C, Kim HJ, Solomon B, Brooks B, Gerber L, Turner M, Domingo D, Hart T, Graf J, Reynolds J, Gropman A, Yanovski J, Collins F, Nabel E, Cannon R, Gahl W, Introne W. Hutchinson-Gilford Progeria syndrome: phenotype and course. New England Journal of Medicine, 358(6): 592-604, 2008.
- Braun A, McArdle J, Nechaev V, Zalewski,C, Brewer C, Drayna, D. Tune deafness: processing melodic errors outside of conscious awareness as reflected by components of the auditory ERP. PLoS ONE, 3(6): e2394, June 11, 2008.
- Reis M, Kim J, Zalewski C, Mastrioianni M, Moore D, Brady R, Schiffman R, Brewer C. Neuropathic and cerebrovascular correlates of hearing loss in Fabry disease. Brain, 130:143-150, 2007.
- Makishima T, Madeo AC, Brewer CC, Zalewski CK, Butman JA, Sachdev V, Arai AE, Holbrook BM, Rosing DR, Griffith AJ. Nonsyndromic hearing loss DFNA10 and a novel mutation of EYA4: evidence for correlation of normal cardiac phenotype with truncating mutations of the Eya domain. American Journal of Medical Genetics, 143(14): 1592-8, 2007.
- Morell R, Brewer C, Dongliang G, Snieder H, Zalewski C, King K, Drayna D, Friedman T. A twin study of auditory processing indicates that dichotic listening ability is a strongly heritable trait.Human Genetics, 122 (1), 103-111, 2007.
- Jagannathan J, Butman JA, Lonser RR, Vortmeyer AA, Zalewski C, Brewer C, Oldfield EH, Kim HJ.Endolymphatic sac tumor demonstrated by intralabyrinthine hemorrhage. Case report.Journal of Neurosurgery, 107(2): 421-425, 2007.
- Jagannathan J, Lonser RR, Stanger RA, Butman JA, Vortmeyer AA, Zalewski C, Brewer C, Surowicz CM, Kim HJ. Cochlear implantation for hearing loss associated with bilateral endolynphatic sac tumors in von Hippel-Lindau disease. Otology and Neurotology, 28(7): 927-930, 2007.
- King K, Makishima T, Zalewski C, Bakalov, V, Griffith A, Bondy C, Brewer C. Analysis of Auditory Phenotype and Karyotype in 200 Females with Turner syndrome. Ear and Hearing, 28:831-841, 2007.
- Doherty ES, Lachbawan F, Hadley DW, Brewer C, Zalewski C, Kim HJ, Solomon B, Robenbaum K, Domingo D, Hart TC, Brooks B, Immken L, Lowry RB, Kimonis V, Shanske AL, Jehee FS, Bueno MRP, Knightley C, McDonald-McGinn D, Zacai E, Muenke M. Muenke syndrome (FGFR3) related craniosynostosis): expansion of the phenotype and review of the literature.American Journal of Medical Genetics, Part A 143A: 3204-3215, 2007.