Professional Education


  • Doctor of Philosophy, Northwestern University (2015)
  • Bachelor of Arts, University of California Berkeley (2004)

Stanford Advisors


All Publications


  • Profiles of Stimulus-Frequency Otoacoustic Emissions from 0.5 to 20 kHz in Humans JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY Dewey, J. B., Dhar, S. 2017; 18 (1): 89-110

    Abstract

    The characteristics of human otoacoustic emissions (OAEs) have not been thoroughly examined above the standard audiometric frequency range (>8 kHz). This is despite the fact that deterioration of cochlear function often starts at the basal, high-frequency end of the cochlea before progressing apically. Here, stimulus-frequency OAEs (SFOAEs) were obtained from 0.5 to 20 kHz in 23 young, audiometrically normal female adults and three individuals with abnormal audiograms, using a low-to-moderate probe level of 36 dB forward pressure level (FPL). In audiometrically normal ears, SFOAEs were measurable at frequencies approaching the start of the steeply sloping high-frequency portion of the audiogram (∼12-15 kHz), though their amplitudes often declined substantially above ∼7 kHz, rarely exceeding 0 dB SPL above 8 kHz. This amplitude decline was typically abrupt and occurred at a frequency that was variable across subjects and not strongly related to the audiogram. In contrast, certain ears with elevated mid-frequency thresholds but regions of normal high-frequency sensitivity could possess surprisingly large SFOAEs (>10 dB SPL) above 7 kHz. When also measured, distortion-product OAEs (DPOAEs) usually remained stronger at higher stimulus frequencies and mirrored the audiogram more closely than SFOAEs. However, the high-frequency extent of SFOAE and DPOAE responses was similar when compared as a function of the response frequency, suggesting that middle ear transmission may be a common limiting factor at high frequencies. Nevertheless, cochlear factors are more likely responsible for complexities observed in high-frequency SFOAE spectra, such as abrupt amplitude changes and narrowly defined response peaks above 10 kHz, as well as the large responses in abnormal ears. These factors may include altered cochlear reflectivity due to subtle damage or the reduced spatial extent of the SFOAE generation region at the cochlear base. The use of higher probe levels is necessary to further evaluate the characteristics and potential utility of high-frequency SFOAE measurements.

    View details for DOI 10.1007/s10162-016-0588-2

    View details for Web of Science ID 000392946400005

    View details for PubMedID 27681700

  • Neuroplastin Isoform Np55 Is Expressed in the Stereocilia of Outer Hair Cells and Required for Normal Outer Hair Cell Function. journal of neuroscience Zeng, W., Grillet, N., Dewey, J. B., Trouillet, A., Krey, J. F., Barr-Gillespie, P. G., Oghalai, J. S., Müller, U. 2016; 36 (35): 9201-9216

    Abstract

    Neuroplastin (Nptn) is a member of the Ig superfamily and is expressed in two isoforms, Np55 and Np65. Np65 regulates synaptic transmission but the function of Np55 is unknown. In an N-ethyl-N-nitrosaurea mutagenesis screen, we have now generated a mouse line with an Nptn mutation that causes deafness. We show that Np55 is expressed in stereocilia of outer hair cells (OHCs) but not inner hair cells and affects interactions of stereocilia with the tectorial membrane. In vivo vibrometry demonstrates that cochlear amplification is absent in Nptn mutant mice, which is consistent with the failure of OHC stereocilia to maintain stable interactions with the tectorial membrane. Hair bundles show morphological defects as the mutant mice age and while mechanotransduction currents can be evoked in early postnatal hair cells, cochlea microphonics recordings indicate that mechanontransduction is affected as the mutant mice age. We thus conclude that differential splicing leads to functional diversification of Nptn, where Np55 is essential for OHC function, while Np65 is implicated in the regulation of synaptic function.Amplification of input sound signals, which is needed for the auditory sense organ to detect sounds over a wide intensity range, depends on mechanical coupling of outer hair cells to the tectorial membrane. The current study shows that neuroplastin, a member of the Ig superfamily, which has previously been linked to the regulation of synaptic plasticity, is critical to maintain a stable mechanical link of outer hair cells with the tectorial membrane. In vivo recordings demonstrate that neuroplastin is essential for sound amplification and that mutation in neuroplastin leads to auditory impairment in mice.

    View details for DOI 10.1523/JNEUROSCI.0093-16.2016

    View details for PubMedID 27581460