Human temporal bone studies have contributed significantly to our understanding of the pathophysiology of hearing and balance disorders. However, despite previous efforts to elucidate the underlying mechanisms of involved in the pathogenesis of temporal bone disorders, there is a tremendous need to create and study temporal bone specimens from patients with well-defined clincial auditory and vestibular disorders who have undergone quantitative auditory and vestibular function testing, and examination by experienced neurotologists. We propose that the advancement of temporal bone science to elucidate the molecular and cellular pathophysiology behind audiovestibular diseases requires a systematic, prospective clinicopathological correlative approach, coupled with rapid fixation and tissue-processing protocols aimed at antigenic and morphological preservation, and the application of the most modern accurate and reliable methodology for quantification and identification of pathological changes in protein and mRNA gene expression. To accomplish this, we propose in aim 1 to expand the National Temporal Bone Hearing and Balance Resource Registry by recruiting donors and obtaining detailed clinical histories and testing on all those pledging temporal bones, in aim 2 to further develop novel human temporal bone processing techniques to maximize morphologic and antigenic and nucleic acie preservation, in aim 3 to apply the modern techniques of immunohistochemistry, unbiased stereology, in situ hybridization and extraction of RNA on microdissected human temporal bone specimens. Additionally, traditional histopathological correlations will be made. DNA will be analyzed for susceptibility genes and correlations between DMA and RNA expression.
In aim 4, we plan to train clinician-scientists and postdoctoral students in temporal bone science and neurotology.
In aim 5, we plan to systematically categorize and digitalize images to allow data sharing, and plan to cooperate fully with the Temporal Bone Research Consortium and to collaborate with other temporal bone research laboratories. We will collaborate with Dr. Kumar Alagramam in the development of RNA extraction using laser capture microdissection, and with Dr. Allen Ryan in the application of in situ hybridization on formalin-fixed paraffin-embedded sections.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Resource-Related Research Projects--Cooperative Agreements (U24)
Project #
5U24DC008635-04
Application #
7673925
Study Section
Special Emphasis Panel (ZDC1-SRB-R (39))
Program Officer
Platt, Christopher
Project Start
2006-09-20
Project End
2011-08-31
Budget Start
2009-09-01
Budget End
2010-08-31
Support Year
4
Fiscal Year
2009
Total Cost
$392,918
Indirect Cost
Name
University of California Los Angeles
Department
Surgery
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Nguyen, Kimanh D; Mowlds, Donald; Lopez, Ivan A et al. (2014) Mu-opioid receptor (MOR) expression in the human spiral ganglia. Brain Res 1590:10-9
Ahmed, Sameer; Vorasubin, Nopawan; Lopez, Ivan A et al. (2013) The expression of glutamate aspartate transporter (GLAST) within the human cochlea and its distribution in various patient populations. Brain Res 1529:134-42
Balaker, Ashley E; Ishiyama, Paul; Lopez, Ivan A et al. (2013) Immunocytochemical localization of the translocase of the outer mitochondrial membrane (Tom20) in the human cochlea. Anat Rec (Hoboken) 296:326-32
Calzada, Audrey P; Lopez, Ivan A; Beltran Parrazal, Luis et al. (2012) Cochlin expression in vestibular endorgans obtained from patients with Meniere's disease. Cell Tissue Res 350:373-84
Calzada, Audrey P; Balaker, Ashley E; Ishiyama, Gail et al. (2012) Temporal bone histopathology and immunoglobulin deposition in Sjogren's syndrome. Otol Neurotol 33:258-66
Calzada, Audrey P; Lopez, Ivan A; Ishiyama, Gail et al. (2012) Otolithic membrane damage in patients with endolymphatic hydrops and drop attacks. Otol Neurotol 33:1593-8
Duong, Trac; Lopez, Ivan A; Ishiyama, Akira et al. (2011) Immunocytochemical distribution of WARP (von Willebrand A domain-related protein) in the inner ear. Brain Res 1367:50-61
Ishiyama, Gail; Geiger, Christopher; Lopez, Ivan A et al. (2011) Spiral and vestibular ganglion estimates in archival temporal bones obtained by design based stereology and Abercrombie methods. J Neurosci Methods 196:76-80
Ishiyama, Gail; Lopez, Ivan A; Beltran-Parrazal, Luis et al. (2010) Immunohistochemical localization and mRNA expression of aquaporins in the macula utriculi of patients with Meniere's disease and acoustic neuroma. Cell Tissue Res 340:407-19
Ishiyama, Akira; Mowry, Sarah E; Lopez, Ivan A et al. (2009) Immunohistochemical distribution of basement membrane proteins in the human inner ear from older subjects. Hear Res 254:1-14

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