Yehoash Raphael

Summary

Affiliation: University of Michigan
Country: USA

Publications

  1. ncbi request reprint Auditory hair cell replacement and hearing improvement by Atoh1 gene therapy in deaf mammals
    Masahiko Izumikawa
    Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, MSRB 3, Room 9303, 1150 W Medical Center Drive, Ann Arbor, Michigan 48109 0648, USA
    Nat Med 11:271-6. 2005
  2. ncbi request reprint p27(Kip1) deficiency causes organ of Corti pathology and hearing loss
    Sho Kanzaki
    Kresge Hearing Research Institute, The University of Michigan Medical School, MSRB III Room 9303, 1150 West Medical Center Drive, Ann Arbor, MI 48109 0648, USA
    Hear Res 214:28-36. 2006
  3. pmc Gene transfer using bovine adeno-associated virus in the guinea pig cochlea
    S B Shibata
    Department of Otolaryngology, Kresge Hearing Research Institute, The University of Michigan, Ann Arbor, MI 48109 5648, USA
    Gene Ther 16:990-7. 2009
  4. pmc BDNF gene therapy induces auditory nerve survival and fiber sprouting in deaf Pou4f3 mutant mice
    H Fukui
    Kresge Hearing Research Institute, Department of Otolaryngology, The University of Michigan, Ann Arbor, MI 48109 5648, USA
    Sci Rep 2:838. 2012
  5. ncbi request reprint Non-sensory cells in the deafened organ of Corti: approaches for repair
    Yehoash Raphael
    Department of Otolaryngology, Kresge Hearing Research Institute, University of Michigan, Ann Arbor, Michigan, USA
    Int J Dev Biol 51:649-54. 2007
  6. ncbi request reprint Severe vestibular and auditory impairment in three alleles of Ames waltzer (av) mice
    Y Raphael
    Kresge Hearing Research Institute, The Department of Otolaryngology, The University of Michigan, Ann Arbor, MI 48109 0648, USA
    Hear Res 151:237-249. 2001
  7. ncbi request reprint Structure and innervation of the cochlea
    Yehoash Raphael
    Kresge Hearing Research Institute, The University of Michigan, MSRB 3, Rm 9303, 1150 W Medical Center Drive, Ann Arbor, MI 48109 0648, USA
    Brain Res Bull 60:397-422. 2003
  8. ncbi request reprint Hearing and hair cells are protected by adenoviral gene therapy with TGF-beta1 and GDNF
    Kohei Kawamoto
    Kresge Hearing Research Institute, Department of Otolaryngology Head and Neck Surgery, The University of Michigan, Ann Arbor, Michigan 48109 0648, USA
    Mol Ther 7:484-92. 2003
  9. ncbi request reprint A glucocorticoid reduces adverse effects of adenovirus vectors in the cochlea
    Shin Ichi Ishimoto
    Kresge Hearing Research Institute, University of Michigan, Ann Arbor, Mich 48109 0506, USA
    Audiol Neurootol 8:70-9. 2003
  10. pmc Cochlear implants and ex vivo BDNF gene therapy protect spiral ganglion neurons
    Darius Rejali
    Kresge Hearing Research Institute, University of Michigan Medical School, Ann Arbor, Michigan, USA, and University Hospitals Warwickshire and Coventry NHS Trust, Coventry CV2 2DX, UK
    Hear Res 228:180-7. 2007

Research Grants

  1. GDNF Protection in the Inner Ear
    Yehoash Raphael; Fiscal Year: 2005
  2. CORE--MORPHOLOGY
    Yehoash Raphael; Fiscal Year: 2002

Detail Information

Publications70

  1. ncbi request reprint Auditory hair cell replacement and hearing improvement by Atoh1 gene therapy in deaf mammals
    Masahiko Izumikawa
    Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, MSRB 3, Room 9303, 1150 W Medical Center Drive, Ann Arbor, Michigan 48109 0648, USA
    Nat Med 11:271-6. 2005
    ..The data suggest a new therapeutic approach based on expressing crucial developmental genes for cellular and functional restoration in the damaged auditory epithelium and other sensory systems...
  2. ncbi request reprint p27(Kip1) deficiency causes organ of Corti pathology and hearing loss
    Sho Kanzaki
    Kresge Hearing Research Institute, The University of Michigan Medical School, MSRB III Room 9303, 1150 West Medical Center Drive, Ann Arbor, MI 48109 0648, USA
    Hear Res 214:28-36. 2006
    ..Manipulations to regulate the time and place of p27 inhibition will be necessary for inducing functionally useful hair cell regeneration...
  3. pmc Gene transfer using bovine adeno-associated virus in the guinea pig cochlea
    S B Shibata
    Department of Otolaryngology, Kresge Hearing Research Institute, The University of Michigan, Ann Arbor, MI 48109 5648, USA
    Gene Ther 16:990-7. 2009
    ..BAAV facilitates efficient transduction of the membranous labyrinth epithelium with minimum pathogenicity and may become clinically applicable for inner ear gene therapy...
  4. pmc BDNF gene therapy induces auditory nerve survival and fiber sprouting in deaf Pou4f3 mutant mice
    H Fukui
    Kresge Hearing Research Institute, Department of Otolaryngology, The University of Michigan, Ann Arbor, MI 48109 5648, USA
    Sci Rep 2:838. 2012
    ..This enhanced nerve survival and regenerative sprouting may improve the outcome of cochlear implant therapy in patients with hereditary deafness...
  5. ncbi request reprint Non-sensory cells in the deafened organ of Corti: approaches for repair
    Yehoash Raphael
    Department of Otolaryngology, Kresge Hearing Research Institute, University of Michigan, Ann Arbor, Michigan, USA
    Int J Dev Biol 51:649-54. 2007
    ..The mitotic potential of these cells should facilitate production of cells for therapies based on recapitulation of development or insertion of stem cells...
  6. ncbi request reprint Severe vestibular and auditory impairment in three alleles of Ames waltzer (av) mice
    Y Raphael
    Kresge Hearing Research Institute, The Department of Otolaryngology, The University of Michigan, Ann Arbor, MI 48109 0648, USA
    Hear Res 151:237-249. 2001
    ..These changes are followed by degeneration of the cochlear and vestibular neuroepithelium...
  7. ncbi request reprint Structure and innervation of the cochlea
    Yehoash Raphael
    Kresge Hearing Research Institute, The University of Michigan, MSRB 3, Rm 9303, 1150 W Medical Center Drive, Ann Arbor, MI 48109 0648, USA
    Brain Res Bull 60:397-422. 2003
    ..This review deals with the structure of the normal mature mammalian cochlea and includes recent data on the molecular organization of the main cell types within the cochlea...
  8. ncbi request reprint Hearing and hair cells are protected by adenoviral gene therapy with TGF-beta1 and GDNF
    Kohei Kawamoto
    Kresge Hearing Research Institute, Department of Otolaryngology Head and Neck Surgery, The University of Michigan, Ann Arbor, Michigan 48109 0648, USA
    Mol Ther 7:484-92. 2003
    ..Our results suggest that the adenovirus-mediated overexpression of GDNF and TGF-beta1 can be used in combination to protect cochlear hair cells and hearing from ototoxic trauma...
  9. ncbi request reprint A glucocorticoid reduces adverse effects of adenovirus vectors in the cochlea
    Shin Ichi Ishimoto
    Kresge Hearing Research Institute, University of Michigan, Ann Arbor, Mich 48109 0506, USA
    Audiol Neurootol 8:70-9. 2003
    ..These data demonstrate that immunosuppressive treatment can reduce the negative consequences of repeated adenovirus-mediated gene therapy...
  10. pmc Cochlear implants and ex vivo BDNF gene therapy protect spiral ganglion neurons
    Darius Rejali
    Kresge Hearing Research Institute, University of Michigan Medical School, Ann Arbor, Michigan, USA, and University Hospitals Warwickshire and Coventry NHS Trust, Coventry CV2 2DX, UK
    Hear Res 228:180-7. 2007
    ..This protective effect decreased in the higher cochlear turns. The data demonstrate the feasibility of combining cochlear implant therapy with ex vivo gene transfer for enhancing spiral ganglion neuron survival...
  11. pmc Over-expression of BDNF by adenovirus with concurrent electrical stimulation improves cochlear implant thresholds and survival of auditory neurons
    JENNIFER A CHIKAR
    Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan Medical School, Ann Arbor, MI 48109 5616, United States
    Hear Res 245:24-34. 2008
    ..These results indicate that the changes in the anatomy of the auditory nerve induced by the combination of Ad.BDNF inoculation and the electrical stimulation used for testing improved functional measures of CI performance...
  12. ncbi request reprint Transgene correction maintains normal cochlear structure and function in 6-month-old Myo15a mutant mice
    Sho Kanzaki
    Kresge Hearing Research Institute, University of Michigan, MSRB III Room 9303, Ann Arbor, MI 48109 0648, USA
    Hear Res 214:37-44. 2006
    ..In addition, excess Myo15a expression has no physiologically significant protective or deleterious effects on hearing of normal mice, suggesting that the dosage of Myo15a may not be problematic for gene therapy...
  13. pmc Effects of hearing preservation on psychophysical responses to cochlear implant stimulation
    Stephen Y Kang
    Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, Ann Arbor, MI 48109 5616, USA
    J Assoc Res Otolaryngol 11:245-65. 2010
    ..We hypothesize that the differences in detection thresholds between groups are caused by the electrical activation of the hair cells in group I animals and/or differences between groups in the condition of the spiral ganglion neurons...
  14. pmc Cochlear infrastructure for electrical hearing
    Bryan E Pfingst
    Department of Otolaryngology, Kresge Hearing Research Institute, University of Michigan, 1150 West Medical Center Drive, Ann Arbor, MI 48109 5616, USA
    Hear Res 281:65-73. 2011
    ..Results of these studies support the efforts to improve the biological infrastructure in the implanted ear and guide strategies which optimize stimulation patterns to match patient-specific conditions in the cochlea...
  15. pmc Response of the flat cochlear epithelium to forced expression of Atoh1
    Masahiko Izumikawa
    Kresge Hearing Research Institute, The University of Michigan Medical School, Ann Arbor, MI 48109 5648, USA
    Hear Res 240:52-6. 2008
    ....
  16. ncbi request reprint Dietary thyroid hormone replacement ameliorates hearing deficits in hypothyroid mice
    I Jill Karolyi
    Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109 0618, USA
    Mamm Genome 18:596-608. 2007
    ..We conclude that TH supplement administered during the critical period of hearing development in mice can prevent deafness associated with congenital hypothyroidism of heterogeneous genetic etiology...
  17. pmc Transgenic BDNF induces nerve fiber regrowth into the auditory epithelium in deaf cochleae
    Seiji B Shibata
    Kresge Hearing Research Institute, Department of Otolaryngology, The University of Michigan, 1150 W Med Cntr Dr, Ann Arbor, MI 48109 5648, USA
    Exp Neurol 223:464-72. 2010
    ..This model also provides a general experimental stage for drawing nerve fibers into a tissue devoid of neurons, and studying the interaction between the nerve fibers and the tissue...
  18. ncbi request reprint Adenovirus-mediated expression of brain-derived neurotrophic factor protects spiral ganglion neurons from ototoxic damage
    Toshihiko Nakaizumi
    KHRI, University of Michigan, Ann Arbor, Mich 48109 0648, USA
    Audiol Neurootol 9:135-43. 2004
    ..CNTF did not significantly enhance the protective effect of BDNF. These data present possible strategies for enhancing SGN survival in cochlear implant procedures...
  19. pmc Deafness and permanently reduced potassium channel gene expression and function in hypothyroid Pit1dw mutants
    Mirna Mustapha
    Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109 5618, USA
    J Neurosci 29:1212-23. 2009
    ..In summary, we suggest that these defects in outer hair cell and strial cell function are important contributors to the hearing impairment in Pit1(dw) mice...
  20. ncbi request reprint Defects in vestibular sensory epithelia and innervation in mice with loss of Chd7 function: implications for human CHARGE syndrome
    Meredith E Adams
    Department of Otolaryngology, The University of Michigan, Ann Arbor, Michigan 48109, USA
    J Comp Neurol 504:519-32. 2007
    ..These observations have important functional implications for understanding the clinical manifestations of CHD7 mutations in humans and for designing therapies to treat inner ear vestibular dysfunction...
  21. pmc Whirler mutant hair cells have less severe pathology than shaker 2 or double mutants
    Mirna Mustapha
    Department of Human Genetics, University of Michigan, 4909 Buhl Building, 1241 East Catherine Street, Ann Arbor, MI 48109 0618, USA
    J Assoc Res Otolaryngol 8:329-37. 2007
    ..This suggests that MYOSIN XV may interact with other proteins besides WHIRLIN that are important for hair cell maturation...
  22. ncbi request reprint Characterization of two transgene insertional mutations at pirouette, a mouse deafness locus
    Hana Odeh
    Department of Otolaryngology Kresge Hearing Research Institute, University of Michigan Medical School, Ann Arbor, Mich 48109 0648, USA
    Audiol Neurootol 9:303-14. 2004
    ....
  23. pmc Detection of pulse trains in the electrically stimulated cochlea: effects of cochlear health
    Bryan E Pfingst
    Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, 1150 West Medical Center Drive, Ann Arbor, Michigan 48109 5616, USA
    J Acoust Soc Am 130:3954-68. 2011
    ..The amount of multipulse integration was correlated with the health of the implanted cochlea with implications for perception of more complex prosthetic stimuli...
  24. pmc Hyaluronic acid enhances gene delivery into the cochlea
    Seiji B Shibata
    Kresge Hearing Research Institute, Department of Otolaryngology, The University of Michigan, Ann Arbor, MI 48109 5648, USA
    Hum Gene Ther 23:302-10. 2012
    ....
  25. pmc Manipulating cell cycle regulation in the mature cochlea
    Ryosei Minoda
    Kresge Hearing Research Institute, The University of Michigan, MSRB 3, Rm 9303, 1150 W Medical Center Drive, Ann Arbor, MI 48109 0648, USA
    Hear Res 232:44-51. 2007
    ..The data also suggest that induced proliferation, by itself, does not generate new hair cells in the cochlea...
  26. ncbi request reprint Math1 gene transfer generates new cochlear hair cells in mature guinea pigs in vivo
    Kohei Kawamoto
    Kresge Hearing Research Institute, Department of Otolaryngology, The University of Michigan, Ann Arbor, Michigan 48109 0648, USA
    J Neurosci 23:4395-400. 2003
    ....
  27. ncbi request reprint Gene-based diagnostic and treatment methods for tinnitus
    Donna M Martin
    Departments of Pediatric Genetics and Human Genetics, University of Michigan, 9220B MSRB 3, Ann Arbor, MI 48109 0648, USA
    Int Tinnitus J 9:3-10. 2003
    ..The use of viral vectors for gene therapy may involve side effects, including immune response to the viral proteins. Treatment with immunosuppressive medications can reduce the negative consequences of adenovirus-mediated gene therapy...
  28. pmc Mature middle and inner ears express Chd7 and exhibit distinctive pathologies in a mouse model of CHARGE syndrome
    Elizabeth A Hurd
    Department of Pediatrics, 3520A MSRB I, University of Michigan, Ann Arbor, MI 48109 5652, USA
    Hear Res 282:184-95. 2011
    ..Together, these data indicate that Chd7(Gt)(/+) mice have combined conductive and sensorineural hearing loss, correlating with changes in both middle and inner ears...
  29. pmc The ATP-dependent chromatin remodeling enzyme CHD7 regulates pro-neural gene expression and neurogenesis in the inner ear
    Elizabeth A Hurd
    Department of Pediatrics, The University of Michigan, Ann Arbor, MI 48109, USA
    Development 137:3139-50. 2010
    ..These data indicate that epigenetic regulation of gene expression by CHD7 must be tightly coordinated for proper development of inner ear neuroblasts...
  30. ncbi request reprint Chronic excitotoxicity in the guinea pig cochlea induces temporary functional deficits without disrupting otoacoustic emissions
    Colleen G Le Prell
    Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan Medical School, Ann Arbor, Michigan 48109 0506, USA
    J Acoust Soc Am 116:1044-56. 2004
    ..Results from the current experiment address the permanence of deficits induced by chronic (14 day) excitotoxic insult as well as deficits in psychophysical detection of longer duration acoustic signals...
  31. pmc Notch signaling and Atoh1 expression during hair cell regeneration in the mouse utricle
    Guo peng Wang
    Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, Ann Arbor, MI 48109, USA
    Hear Res 267:61-70. 2010
    ..qRTPCR data showed a post trauma decrease of Hes5 and an increase in Atoh1. Atoh1 up-regulation may either be a result of Hes5 down-regulation or mediated by another signaling pathway...
  32. ncbi request reprint Transgene expression in neonatal mouse inner ear explants mediated by first and advanced generation adenovirus vectors
    Sho Kanzaki
    Kresge Hearing Research Institute, The University of Michigan, MSRB 3, Room 9303, Ann Arbor, MI 48109 0648, USA
    Hear Res 169:112-20. 2002
    ..The data demonstrate that differentiating HCs and SCs in mouse explants can be transduced by adenovirus vectors, suggesting that cultures of mouse ears are a valuable model for developing inner ear gene therapy protocols...
  33. pmc Age-related changes in cochlear gene expression in normal and shaker 2 mice
    Tzy Wen L Gong
    Kresge Hearing Research Institute, Department of Otolaryngology Head Neck Surgery, University of Michigan Medical School, Ann Arbor, MI 48109 0648, USA
    J Assoc Res Otolaryngol 7:317-28. 2006
    ..These results identified potential cellular pathways associated with myosin XV defects, and age-associated molecular events that are likely to be involved in maturation of the cochlea and auditory function...
  34. ncbi request reprint The fate of outer hair cells after acoustic or ototoxic insults
    Karen A Abrashkin
    Kresge Hearing Research Institute, Department of Otolaryngology, Rm 9301 MSRB 3, Ann Arbor, MI 48109 0648, USA
    Hear Res 218:20-9. 2006
    ..The data show that cochlear supporting cells surround the corpses and/or debris of degenerated outer hair cells, and suggest that outer hair cell remains are phagocytosed by supporting cells within the epithelium...
  35. pmc The use of a dual PEDOT and RGD-functionalized alginate hydrogel coating to provide sustained drug delivery and improved cochlear implant function
    JENNIFER A CHIKAR
    Neuroscience Program, University of Michigan, 4137 Undergraduate Research Bldg, 204 Washtenaw Ave, Ann Arbor, MI 48109 2215, USA
    Biomaterials 33:1982-90. 2012
    ..This coating is non-cytotoxic, clinically relevant, and has the potential to significantly improve the cochlear implant user's experience...
  36. pmc Visualization of spiral ganglion neurites within the scala tympani with a cochlear implant in situ
    JENNIFER A CHIKAR
    Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, 1150 W Medical Center Drive, Room 4605 Med Sci II, Ann Arbor, MI 48109 5616, USA
    J Neurosci Methods 179:201-7. 2009
    ..This paper presents a novel histological technique that enables simultaneous visualization of the in situ cochlear implant and neurofilament-labeled nerve processes within the scala tympani, and the spatial relationship between them...
  37. pmc The role of bone morphogenetic protein 4 in inner ear development and function
    Marsha N Blauwkamp
    Cellular and Molecular Biology Program, 2966 Taubman Medical Library, University of Michigan, Ann Arbor, MI 48109 0619, USA
    Hear Res 225:71-9. 2007
    ..Thus Bmp4(+/-) mice have structural and functional deficits in the inner ear...
  38. ncbi request reprint Glial cell line-derived neurotrophic factor and chronic electrical stimulation prevent VIII cranial nerve degeneration following denervation
    Sho Kanzaki
    Kresge Hearing Research Institute, University of Michigan, Ann Arbor, Michigan 48109 0648, USA
    J Comp Neurol 454:350-60. 2002
    ..We suggest that GDNF/ES combined treatment in cochlear implant recipients will improve auditory perception. These findings may have implications for the prevention and treatment of other neurodegenerative processes. ...
  39. pmc Age-related changes in expression of CTL2/SLC44A2 and its isoforms in the mouse inner ear
    Lisa A Beyer
    Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI 48109, USA
    Hear Res 282:63-8. 2011
    ..The changes we observed in isoform distribution are indicative of differential developmental roles and age related changes between the two isoforms of CTL2/SLC44A2 in the inner ear...
  40. pmc Nestin-expressing cells in the developing, mature and noise-exposed cochlear epithelium
    Reiko Watanabe
    Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, Ann Arbor, MI 48109 5648, USA
    Mol Cell Neurosci 49:104-9. 2012
    ..As such, this population of cells could serve to generate cochlear stem cells for research and potential therapy, and may be a target for treatments based on induced transdifferentiation of endogenous cochlear cells...
  41. pmc Nerve maintenance and regeneration in the damaged cochlea
    Seiji B Shibata
    Kresge Hearing Research Institute, Department of Otolaryngology, The University of Michigan, 1150 W Medical Center Dr, Ann Arbor, MI 48109 5648, USA
    Hear Res 281:56-64. 2011
    ..Research on enhancing the biological infrastructure of the deafened cochlea in order to improve cochlear implant efficacy is of immediate clinical importance...
  42. pmc Electromotile hearing: acoustic tones mask psychophysical response to high-frequency electrical stimulation of intact guinea pig cochleae
    Colleen G Le Prell
    Kresge Hearing Research Institute, 1301 East Ann Street, Ann Arbor, Michigan 48109 0506, USA
    J Acoust Soc Am 120:3889-900. 2006
    ..Based on the masking effects, it is concluded that sinusoidal electric stimulation of the intact cochlea results in perception of a tonal (rather than a broadband or noisy) sound at a frequency of 8 kHz or above...
  43. ncbi request reprint Strategies for replacing lost cochlear hair cells
    Ryosei Minoda
    Kresge Hearing Research Institute, The University of Michigan Medical School, MSRB III Room 9303, Ann Arbor, MI 48109 0648, USA
    Neuroreport 15:1089-92. 2004
    ..Consequently, sensorineural hearing loss is permanent. In designing therapy for sensorineural deafness, the most important task is to find a way to generate new cochlear hair cells to replace lost cells...
  44. pmc Gene therapy for the inner ear
    Hideto Fukui
    Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, 1150 West Medical Center Dr, Ann Arbor, MI 48109 5648, USA
    Hear Res 297:99-105. 2013
    ..We then review the progress toward using gene transfer for therapies in both auditory and balance systems, and discuss the technological milestones needed to advance to clinical application of these methods...
  45. pmc Localized cell and drug delivery for auditory prostheses
    Jeffrey L Hendricks
    Department of Biomedical Engineering, The University of Michigan, 1107 Gerstacker Building, 2200 Bonisteel Boulevard, Ann Arbor, MI 48109 2099, USA
    Hear Res 242:117-31. 2008
    ..Together, these methods and pharmaceutical agents can be used to optimize the tissue-device interface for improved AP safety and effectiveness...
  46. pmc Notch signaling and Hes labeling in the normal and drug-damaged organ of Corti
    Shelley A Batts
    Kresge Hearing Research Institute, University of Michigan Medical School, MSRB 3, 1150 West Medical Center Drive, Ann Arbor, MI 48109 5648, USA
    Hear Res 249:15-22. 2009
    ..Additionally, since Hes activity antagonizes the transcription of pro-sensory Atoh1, the presence of Hes after a lesion may prohibit the occurrence of transdifferentiation in the surviving supporting cells...
  47. ncbi request reprint Loss of Chd7 function in gene-trapped reporter mice is embryonic lethal and associated with severe defects in multiple developing tissues
    Elizabeth A Hurd
    Department of Pediatrics, The University of Michigan Medical Center, Ann Arbor, Michigan 48109 0652, USA
    Mamm Genome 18:94-104. 2007
    ..These studies demonstrate the utility of Chd7(Gt) as a reporter-tagged loss-of-function allele for future studies exploring developmental mechanisms of Chd7 deficiency...
  48. ncbi request reprint Transdifferentiation and its applicability for inner ear therapy
    Shelley A Batts
    Department of Otolaryngology, Kresge Hearing Research Institute, MSRB 3, Room 9301, Ann Arbor, MI 48109 0648, USA
    Hear Res 227:41-7. 2007
    ..The hope is that this information can be used to design therapies to replace lost hair cells and restore impaired hearing in humans...
  49. ncbi request reprint Cell division and maintenance of epithelial integrity in the deafened auditory epithelium
    Young Ho Kim
    Department of Otolaryngology, Kresge Hearing Research Institute, Ann Arbor, Michigan 48109, USA
    Cell Cycle 6:612-9. 2007
    ..Presence of mitosis in the tissue presents therapeutic opportunities for gene transfer and stem cells therapies...
  50. pmc Mutations in Grxcr1 are the basis for inner ear dysfunction in the pirouette mouse
    Hana Odeh
    Department of Otolaryngology, Kresge Hearing Research Institute, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Am J Hum Genet 86:148-60. 2010
    ..Our results suggest that deafness in pirouette mutants is associated with loss of GRXCR1 function in modulating actin cytoskeletal architecture in the developing stereocilia of sensory hair cells...
  51. ncbi request reprint WDR1 colocalizes with ADF and actin in the normal and noise-damaged chick cochlea
    Seung Ha Oh
    Kresge Hearing Research Institute, Department of Otolaryngology Head and Neck Surgery, The University of Michigan Medical School, Ann Arbor, MI 48109 0506, USA
    J Comp Neurol 448:399-409. 2002
    ..These results suggest that WDR1 may play a role either in restoring cytoskeletal integrity in supporting cells or in a cell signaling pathway required for regeneration...
  52. ncbi request reprint From gene identification to gene therapy
    Sho Kanzaki
    Kresge Hearing Research Institute, Ann Arbor, Mich, USA
    Audiol Neurootol 7:161-4. 2002
    ..Future identification of the genes that are important for protection and regeneration, along with improved gene transfer technology, will allow the use of gene therapy for treating hereditary and environmental inner ear disease...
  53. pmc The use of neurotrophin therapy in the inner ear to augment cochlear implantation outcomes
    Cameron L Budenz
    Kresge Hearing Research Institute, University of Michigan, Ann Arbor, Michigan 48109, USA
    Anat Rec (Hoboken) 295:1896-908. 2012
    ..While further research must be done before these therapies can be applied clinically, neurotrophin therapies for the inner ear show great promise in enhancing CI outcomes and the treatment of hearing loss...
  54. ncbi request reprint Mutation of the novel gene Tmie results in sensory cell defects in the inner ear of spinner, a mouse model of human hearing loss DFNB6
    Kristina L Mitchem
    Department of Otolaryngology Kresge Hearing Research Institute, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    Hum Mol Genet 11:1887-98. 2002
    ..The spinner mutant is thus a valuable model for insight into mechanisms of human deafness and development of sensory cell function...
  55. ncbi request reprint PITX2 is required for normal development of neurons in the mouse subthalamic nucleus and midbrain
    Donna M Martin
    Department of Pediatrics and Communicable Diseases, The University of Michigan, Ann Arbor, MI 48109, USA
    Dev Biol 267:93-108. 2004
    ..Our results suggest a role for Pitx2 in regulating regionally specific terminal neuronal differentiation in the developing ventrolateral thalamus and midbrain...
  56. ncbi request reprint The cytocaud: a hair cell pathology in the waltzing Guinea pig
    Sho Kanzaki
    Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI 48109, USA
    Audiol Neurootol 7:289-97. 2002
    ..Our data suggest that the cytocauds in vestibular hair cells of the waltzing guinea pig are highly organized structures associated with a failure to detach from the basement membrane...
  57. ncbi request reprint Myo15 function is distinct from Myo6, Myo7a and pirouette genes in development of cochlear stereocilia
    I Jill Karolyi
    Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109 0638, USA
    Hum Mol Genet 12:2797-805. 2003
    ..These data suggest that the function of Myo15 is distinct from that of Myo6, Myo7a or pi in development and/or maintenance of stereocilia...
  58. pmc Connexin 26 null mice exhibit spiral ganglion degeneration that can be blocked by BDNF gene therapy
    Yohei Takada
    Kresge Hearing Research Institute, Department of Otolaryngology Head and Neck Surgery, University of Michigan, 1150 West Medical Center Dr, Ann Arbor, MI 48109 5648, USA Department of Otolaryngology, Kansai Medical University, 2 3 1, Shinmachi, Hirakata, Osaka 573 1191, Japan
    Hear Res 309:124-35. 2014
    ....
  59. pmc siRNA targeting Hes5 augments hair cell regeneration in aminoglycoside-damaged mouse utricle
    Jae Yun Jung
    KHRI, Otolaryngology, Head and Neck Surgery, The University of Michigan, Ann Arbor, Michigan 48109 5648, USA
    Mol Ther 21:834-41. 2013
    ..The data suggest that siRNA technology may be useful for inducing repair and regeneration in the inner ear and that the Notch signaling pathway is a potentially useful target for specific gene expression inhibition...
  60. pmc Long-term effects of acoustic trauma on electrically evoked otoacoustic emission
    Kirin Halsey
    Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan Medical School, Ann Arbor, MI 48109 0506, USA
    J Assoc Res Otolaryngol 6:324-40. 2005
    ..The presence of EEOAE fine structure in the postexposure response is an indicator of TTS in advance of CAP recovery. The results suggest that the EEOAE might be used to differentiate the mechanisms associated with TTS and PTS...
  61. ncbi request reprint Identification and characterization of choline transporter-like protein 2, an inner ear glycoprotein of 68 and 72 kDa that is the target of antibody-induced hearing loss
    Thankam S Nair
    Department of Otolaryngology Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan 48109 0506, USA
    J Neurosci 24:1772-9. 2004
    ..Sera from patients with autoimmune hearing loss bind to guinea pig inner ear with the same pattern as CTL2 antibodies. Thus, CTL2 is a possible target of autoimmune hearing loss in humans...
  62. doi request reprint Have you heard? Viral-mediated gene therapy restores hearing
    Donna M Martin
    Department of Pediatrics, The University of Michigan, Ann Arbor, MI 48109, USA
    Neuron 75:188-90. 2012
    ..In this issue of Neuron, Akil et al. (2012) show that AAV-mediated introduction of wild-type VGLUT3 in the genetically deaf mouse cochlea results in significantly improved hearing...
  63. ncbi request reprint Manipulating gene expression in the mature inner ear
    Mark A Crumling
    Kresge Hearing Research Institute, The University of Michigan, MSRB III Room 9303, Ann Arbor, MI 48109 0648, USA
    Brain Res 1091:265-9. 2006
    ....
  64. pmc Future approaches for inner ear protection and repair
    Seiji B Shibata
    Kresge Hearing Research Institute, Department of Otolaryngology, The University of Michigan, Ann Arbor, MI 48109 5648, USA
    J Commun Disord 43:295-310. 2010
    ..Here we aim to equip the provider with information about some of the progress made for protective and reparative approaches for treating inner ears...
  65. pmc COQ6 mutations in human patients produce nephrotic syndrome with sensorineural deafness
    Saskia F Heeringa
    Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA
    J Clin Invest 121:2013-24. 2011
    ..These data suggest that coenzyme Q10-related forms of SRNS and hearing loss can be molecularly identified and potentially treated...
  66. ncbi request reprint Prospects for gene therapy in hearing loss
    Karen B Avraham
    Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
    J Basic Clin Physiol Pharmacol 14:77-83. 2003
    ..This review is not meant to be comprehensive, but to highlight some of the most recent developments in the field. Several recent reviews have described potential therapeutic approaches...
  67. ncbi request reprint Cochlear pathology, sensory cell death and regeneration
    Yehoash Raphael
    KHRI, The University of Michigan Medical School, Ann Arbor 48109, USA
    Br Med Bull 63:25-38. 2002
    ..This chapter discusses the potential for some of these approaches...
  68. ncbi request reprint Gene transfer into supporting cells of the organ of Corti
    Shin Ichi Ishimoto
    University of Tokyo, Department of Otolaryngology, Japan
    Hear Res 173:187-97. 2002
    ..The ability to deliver transgenes that are expressed in the supporting cells is an important step in the development of clinically applicable treatments that involve hair cell regeneration...
  69. ncbi request reprint Claudin 14 knockout mice, a model for autosomal recessive deafness DFNB29, are deaf due to cochlear hair cell degeneration
    Tamar Ben-Yosef
    Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA
    Hum Mol Genet 12:2049-61. 2003
    ..Our data suggest that the TJ complex at the apex of the reticular lamina requires claudin 14 as a cation-restrictive barrier to maintain the proper ionic composition of the fluid surrounding the basolateral surface of outer hair cells...
  70. ncbi request reprint Antioxidant gene therapy can protect hearing and hair cells from ototoxicity
    Kohei Kawamoto
    Department of Otolaryngology, Kansai Medical University, 10 15 Fumizono cho, Moriguchi, Osaka 570 8506, Japan
    Mol Ther 9:173-81. 2004
    ..Furthermore, they confirm that reactive oxygen species contribute to aminoglycoside ototoxicity and suggest antioxidant gene therapy as a potential therapeutic strategy to reduce inner ear oxidative stress...

Research Grants4

  1. GDNF Protection in the Inner Ear
    Yehoash Raphael; Fiscal Year: 2005
    ..The data we propose to generate will enhance our understanding of the mechanisms of action of GDNF in normal and injured inner ear epithelia, knowledge that may eventually lead to better clinical treatments ..
  2. CORE--MORPHOLOGY
    Yehoash Raphael; Fiscal Year: 2002
    ..Dr. Raphael will also be involved in preparing the data for presentation in meetings or peer reviewed papers. ..