General Hearing Health

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Nicole Tin-Lok Jiam, M.D.

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Nicole Tin-Lok Jiam, M.D.

Mass Eye and Ear

Age-specific cochlear implant programming for optimal hearing performance

Cochlear implants (CI) offer life-altering hearing restoration for deafened individuals who no longer benefit from hearing aid technologies. Despite advances in CI technology, recipients struggle to process complex sounds in real-world environments, such as speech-in-noise and music. Poor performance results from artifacts of the implants (e.g., adjacent channel interaction, distorted signal input) and age-specific biological differences (e.g., neuronal health, auditory plasticity). Our group determined that children with CIs require a better signal input than adults with CIs to achieve the same level of performance. Additional evidence demonstrates that auditory signal blurring in adults is less impactful on performance outcomes. These findings imply that age should be considered when programming a CI. However, the current clinical practice largely adopts a one-size-fits-all approach toward CI management and uses programming parameters defined by adult CI users. Our project’s main objective is to understand how to better program CIs in children to improve complex sound processing by taking into context the listening environment (e.g., complex sound processing in a crowded room), differences between age groups, and variations in needs or anatomy between individuals.

Christina L. Kaiser, Ph.D.

Christina L. Kaiser, Ph.D.

Boston University School of Medicine

An active role for the supporting cell cytoskeleton in controlling hair cell death and regeneration

Cochlear hair cells are the primary targets of most damaging agents. When these cells are lost in humans and other mammals, the resultant hearing loss is permanent. However, chickens and other avian species have the ability to replace lost cochlear hair cells. Cochlear hair cell regeneration occurs through two different mechanisms: Direct transdifferentiation (DT) and mitotic proliferation. In DT, supporting cells directly alter their gene expression to become new hair cells. Alternatively, in mitotic proliferation, normally quiescent supporting cells are induced to proliferate and differentiate into new hair cells and new supporting cells following the death and ejection of the original sensory cells. The experiments in this research are designed to examine how supporting cells regulate hair cell death and how this subsequently regulates supporting cell proliferation. Additionally, we are trying to prevent both the death and ejection of cochlear hair cells. If cochlear hair cells can be “trapped” and “rescued” by treatment with various inhibitors, these compounds may be useful therapeutic tools in hearing loss prevention.

Ravinder Kaur, Ph.D.

Ravinder Kaur, Ph.D.

Rochester General Hospital Research Institute
Differential Virulence gene expression of S. pneumoniae and Haemophilus influenzae in children with Acute Otitis Media & modulation of innate immune responses

Middle ear infections are the most common infectious disease among children leading to the use of antibiotics. Middle ear infections are typically followed by 4-12 weeks of middle ear effusion during which time children have diminished hearing leading to temporary delayed speech and language development. In developing countries, permanent hearing loss is not uncommon. Non-typeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae (Spn) are the two main bacteria that cause middle ear infections and are the target for new vaccine development. In the funded research, expression of various vaccine candidate proteins of NTHi and Spn in the nose (where middle ear infections start) and in the middle ear (where infections cause hearing loss) will be compared. Gene expression of the studied NTHi and Spn vaccine targets might be modulated by innate immunity of the host during disease progression and this too will be studied.

Research area: Middle Ear

Long-term goal of research: To develop a vaccine to prevent middle ear infections, thereby reducing hearing loss from this common childhood infection. Towards this goal here we will evaluate several vaccine candidates of the most common causes of middle ear infections to determine whether immunity induced by vaccination will be effective to rid the child of the bacteria when they reside in the nose and/or when they gain entry to the middle ear. We will also study how the gene expression of the studied vaccine targets might be influenced by the child’s immunity system.

Ravinder Kaur, Ph.D. is a Research Scientist at the Rochester General Hospital Research Institute. Kaur’s research focuses on the pathogenesis of middle ear infections and immune response of children to those infections with a goal of facilitating a vaccine to prevent hearing loss.

Judith Kempfle, M.D.

Judith Kempfle, M.D.

Click to download a PDF of Dr. Kempfle’s Meet the Researcher profile.

Subong Kim, Ph.D.

Subong Kim, Ph.D.

Purdue University
Influence of individual pathophysiology and cognitive profiles on noise tolerance and noise reduction outcomes

Listening to speech in noisy environments can be significantly challenging for people with hearing loss, even with help from hearing aids. Current digital hearing aids are commonly equipped with noise-reduction algorithms; however, noise-reduction processing introduces inevitable distortions of speech cues while attenuating noise. It is known that hearing-impaired listeners with similar audiograms react very differently to background noise and noise-reduction processing in hearing aids, but the biological mechanisms contributing to that variability is particularly understudied.

This project is focused on combining an array of physiological and psychophysical measures to obtain comprehensive hearing and cognitive profiles for listeners. We hope this approach will allow us to explain individual noise tolerance and sensitivity to speech-cue distortions induced by noise-reduction processing in hearing aids. With these distinct biological profiles, we will have a deeper understanding of individual differences in listeners and how those profiles affect communication outcomes across patients who are clinically classified with the same hearing status. This study’s results will assist in the development of objective diagnostics for hearing interventions tailored to individual needs.

Yayoi S. Kikkawa, M.D., Ph.D.

Yayoi S. Kikkawa, M.D., Ph.D.

University of Texas Southwestern Medical Center

Molecular and morphological analysis of protocadherin 15 in vestibular stereocilia development

Stereocilia of the inner ear hair cells are micro-scale mechanosensors which convert mechanical forces into electrochemical signals and its precise integrity is critical for hearing and balance. However, the molecular mechanism that regulates stereocilia integrity is not well understood. This proposal focuses on a cadherin-like protein, protocadherin 15 (Pcdh15). Mutations in human Pcdh15 cause Usher syndrome (USH type 1F), the leading cause of combined hearing and vision loss. The molecular characterization of Pcdh15 will lay the foundation for therapeutic strategies not only for Usher syndrome but also for other inner ear disorders associated with abnormalities of hair cell transduction.

Takako Kondo, Ph.D.

Takako Kondo, Ph.D.

Indiana University School of Medicine

Role of T1x3 signaling in inner ear sensory neuron development

The primary goal of this study is to elucidate novel functions of the Y1x3-class homeobox gene 3 (T1x3) in the development of inner ear sensory neurons. The specific aims in this study are: (1) To test whether T1x3 is required for normal development of inner ear sensory neurons, and (2) To test whether T1x3 is sufficient for multipotent progenitor cells in the early embryonic ear to become competent to commit to a glutamatergic neural subtype. The long-term goal of this study is to clearly understand the molecular mechanisms underlying specification of auditory and vestibular neurons.

Kelvin Y. Kwan, Ph.D.

Kelvin Y. Kwan, Ph.D.

Rutgers University
Identification of Transcription Factors for Hair Cell Regeneration

In mammals, when hair cells die from ototoxic drugs or loud noises, they are not replaced. Kwan’s efforts are focused on identifying transcription factors that promote repopulation and replacement of lost sensory hair cells. Transcription factors are DNA binding proteins that play crucial roles in global gene regulation. By repurposing transcription factors that are normally expressed during hair cell development, he plans to promote regeneration by controlled cell division to repopulate lost hair cells before differentiating nascent cells into hair cells.

Research area: hair cell regeneration

Long-term goal of research: To use a cocktail of small molecules that activates expression of transcription factors or their associated signaling pathways in order to promote functional auditory hair cell regeneration and alleviate hearing loss.

Kristy J. Lawton, Ph.D.

Kristy J. Lawton, Ph.D.

Washington State University Vancouver
Characterizing noise-induced synaptic loss in the zebrafish lateral line

Recent findings indicate that noise levels thought to be safe for auditory sensory hair cells may actually damage hearing at the level of peripheral auditory synapses. Little is known about this type of damage, which is usually not detectable using traditional audiograms and so has been dubbed “hidden hearing loss.” This project will study noise-induced hearing loss using zebrafish, where the auditory sensory cells are easily accessible and highly similar to those in humans, in order to uncover mechanisms of synaptic damage due to noise exposure. It will use a combination of techniques including immunohistochemistry and calcium imaging to directly examine the timing and extent of noise damage on peripheral auditory synapses.

Snezana Levic, Ph.D.

Snezana Levic, Ph.D.

University of California Davis

Mechanism of hair cell development and regeneration

Hair cells (HCs) convert sound signals into electrical impulses in the cochlea with remarkable precision and sensitivity. Our long-term goals are to stimulate HC regeneration in human inner ears in a controlled fashion, and to enable the functional innervation of the regenerated HC's by spiral ganglion neurons (SGNs). To do this, the functional mechanisms of the development of HCs must be understood. In the developing systems, there is temporal overlap between ion channel development, spontaneous activity and activity-dependent development. Therefore, APs could serve both intrinsic (ion channel expression) and extrinsic (neuronal refinement) development roles. We have identified differential patterning of APs in the developing cochlear axis that reflects differences in expression of ionic conductances. We will test the prediction that the activity of HCs influenced that of its neighbors, including the preservation of the synaptic transmission between auditory nerve and HCs. The proposed study will increase our understanding of the activity dependent development in the auditory system.

Geng-Lin Li, Ph.D.

Geng-Lin Li, Ph.D.

Oregon Health & Science University

Auditory signal coding at the hair cell ribbon synapses

The sense of hearing starts at hair cells, which connect to afferent fibers via ribbon synapses. Across these synapses, auditory signals contained in graded potentials on hair cells are transformed into all-or-none spikes on afferent fibers. Therefore, these synapses face the tremendous challenge of continuous coding of auditory signals over a remarkable dynamic range. It is not well understood how these specialized synapses achieve their extraordinary ability to release transmitters continuously. This has greatly impaired our ability to treat hearing loss. The long-term objective of this study is to investigate mechanisms of synaptic transmission and strategies for auditory signal coding at this very first chemical synapse along the auditory pathway. In two years, the specific aims are: 1) To study multivesicular release and its mechanisms; 2) To determine how the release of vesicles is transformed to spikes on afferent fibers; 3) To investigate short-term plasticity and how it helps the coding of auditory signals.

Yan Li, Ph.D.

Yan Li, Ph.D.

New York University School of Medicine

Mouse models of human syndromic hearing loss linked to mutant MYH9 alleles

Mutations within the nonmuscle myosin heavy chain type IIA (MYH9) have been linked to human hearing loss. The study will examine the biological role of MYH9 in hearing and the role of its mutant alleles MYH9R702C in hearing loss with the goal of developing and characterizing transgenic mouse models that express the mutant alleles MYH9R702C which is linked to syndromic hereditary hearing loss in humans. Characterizing these mice models will lead to elucidation of the role of MYH9 in hearing and help to development of therapeutic strategies for circumventing hearing loss due to MYH9 mutation.

Patricia A. Loomis, Ph.D.

Patricia A. Loomis, Ph.D.

Rosalind Franklin University of Medicine and Science

Splicing regulation of pre-mRNA generated from the deafness-associated Espin gene

The goal of this proposal is to determine how Espin gene expression is controlled at the level of RNA processing. Loss of function mutational analysis will identify RNA sequences on the Espin pre-mRNA that are essential for alternative splicing reactions. Proteins that bind the regulatory RNA sequences will be identified by UV-cross- linking, Western blotting and immunoprecipitation. Correlation of the in vitro analysis with in vivo activity will be accomplished through modulating by RNAi and overexpression the levels of these proteins in HeLa cells transfected with Espin mini-gene constructs containing genomic sequence corresponding to the alternatively spliced exon and flanking introns.

Sean Eric Low, Ph.D.

Sean Eric Low, Ph.D.

Rockefeller University
Ascertaining the contribution of Piezo proteins to Mechano-transduction in Zebrafish hair cells

The proteins that mediate the transformation of mechanical forces into electrical signals within the sensory cells that convey the senses of hearing and balance have yet to be identified. This lack of knowledge has undoubtedly hindered the identification of therapeutic compounds capable of alleviating the complications that arise from disorders in hearing and balance, such as deafness and vertigo. Recently, a member of the novel piezo protein family has been shown to contribute to cutaneous mechano-sensation, raising the possibility that related family members may contribute to hearing and balance. Dr. Low will utilize the simple vertebrate commonly known as zebrafish, to address this possibility.

Research area: Fundamental Auditory Research

Long term goal of research: To identify therapeutic agents that can restore normal hearing and balance in individuals who have either lost these senses, or suffer from conditions caused by abnormal activity in the sensory cells that mediate them.

Sean Low Ph.D. received a B.S. in Cellular and Molecular Biology in 2001, and a Ph.D. in Neuroscience in 2008 from the University of Michigan. Desiring to focus on sensory transduction, Low sought out a postdoctoral position in the Saint-Amant lab at the University of Montréal from 2009 – 2011, where he examined the role of a Piezo protein in cutaneous mechano-transduction. These studies evolved into an interest in mechano-transduction processes in general, and a second postdoctoral position with Dr. Hudspeth at The Rockefeller University beginning in 2011.

Anat Lubetzky, Ph.D.

Anat Lubetzky, Ph.D.

New York University
A balancing act in hearing and vestibular loss: assessing auditory contribution to multisensory integration for postural control in an immersive virtual environment

Humans are surrounded by sensory information and need to select the most reliable ones in order to maintain balance and disregard input that might make us fall. This is called “weighting” and “reweighting” of sensory inputs. This project uses a virtual reality, head-mounted display (HMD) application to test balance with varying sensory cues, including visual, somatosensory, and auditory. With this application, an individual’s ability to weight and reweight visual and auditory information based on their head and eye movement and their postural sway can be identified. This method has been successfully used in prior studies to test responses to visual changes. The novelty of this project includes: the addition of auditory cues scaled to well-established visual cues; the measurement of head movement via the HMD; and the portability, simplicity, and affordability of the HMD system, which increases the likelihood of future clinical translation of this assessment. In this current pilot study, 12 individuals with unilateral sensorineural hearing loss will be compared with 12 individuals with unilateral peripheral vestibular hypofunction and with 24 healthy controls. Wearing the HMD, they will go through a series of postural tasks with several combinations of visual and auditory cues of two intensity levels while standing on either a stable floor (all somatosensory cues available) or a compliant foam (to reduce somatosensory input). Their postural sway and head movement responses to the stimuli will be calculated, and gaze patterns among the groups will be compared, along with exploring whether changes in eye position can explain changes in head movement.

Anna Majewska, Ph.D.

Anna Majewska, Ph.D.

University of Rochester

Cortical synaptic plasticity in a mouse model of moderate sensorineural hearing loss

The development of cortical networks is exquisitely sensitive to patterned activity elicited through sensory stimulation. Although much is known about somatosensory and visual cortical development, very little is known about the development of auditory cortex network connectivity. Changes in hearing that occur as a result of defects in sensation at the cochlea likely affect the development of higher brain areas which process auditory information. Our research will explore changes in the neural networks that process auditory stimuli in the cortex in a mouse model where prestin, a protein crucial for outer hair cell electromotile function is absent during development. We will address this question by looking at synaptic sites which link individual neurons into networks and compare their density, distribution and dynamic remodeling in control and prestin-null mice. We hypothesize that changes in both static and dynamic synaptic structure will be present in the auditory cortex of prestin-null mice, suggesting that cortical auditory networks are altered by degraded hearing during development. This work will shed light on synaptic mechanisms and possible treatments of developmentally acquired hearing loss.

Ani Manichaikul, Ph.D.

Ani Manichaikul, Ph.D.

University of Virginia
Susceptibility to chronic otitis media: translating gene to function

Each year in the United States, over $5 billion is spent on healthcare for inflammation of the middle ear (ME) known as Otitis Media (OM) in children. Some children develop chronic middle ear infections known as chronic otitis media with effusion and/or recurrent otitis media (COME/ROM). Our goal is to find genetic factors that increase risk for COME/ROM in children. The discovery of causal variants would increase knowledge of novel genes and pathways involved in COME/ROM pathogenesis.

Research area: Otitis Media; Genetics

Long-term goal of research: To improve the clinical prevention of chronic infections; therefore decreasing pediatric antibiotic use, surgery, and deafness.

Adam Markaryan, Ph.D.

Adam Markaryan, Ph.D.

University of Chicago

Mitochondrial DNA deletions and cochlear element degeneration in presbycusis

The long term goal of the Bloom Temporal Bone Laboratory is to understand the molecular mechanisms involved in age-related hearing loss and develop a rationale for therapy based on this information. This project will quantify the mitochondrial DNA common deletion level and total deletion load in the cochlear elements obtained from individuals with presbycusis and normal hearing controls. The relationship between deletion levels, the extent of cochlear element degeneration, and the severity of hearing loss will be explored in human archival tissues to clarify the role of deletions in presbycusis.

This research award is funded by The Burch-Safford Foundation Inc.

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Matthew Masapollo, Ph.D.

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Matthew Masapollo, Ph.D.

University of Florida
Contributions of auditory and somatosensory feedback to speech motor control in congenitally deaf 9- to-10-year-olds and adults

Cochlear implants have led to stunning advances in prospects for children with congenital hearing loss to acquire spoken language in a typical manner, but problems persist. In particular, children with CIs show much larger deficits in acquiring sensitivity to the individual speech sounds of language (phonological structure) than in acquiring vocabulary and syntax. This project will test the hypothesis that the acquisition of detailed phonological representations would be facilitated by a stronger emphasis on the speech motor control associated with producing those representations. This approach is novel because most interventions for children with CIs focus strongly on listening to spoken language, which may be overlooking the importance of practice in producing language, an idea we will examine. To achieve that objective, we will observe speech motor control directly in speakers with congenital hearing loss and CIs, with and without sensory feedback.

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Jameson Mattingly, M.D.

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Jameson Mattingly, M.D.

The Ohio State University
Differentiating Ménière's disease and vestibular migraine using audiometry and vestibular threshold measurements

Patients presenting with recurrent episodic vertigo (dizziness), such as Ménière's disease (MD) and vestibular migraine (VM), can present a diagnostic challenge as they can both produce recurrent vertigo, tinnitus, motion intolerance, and hearing loss. Further complicating this issue is that the diagnosis of each is based upon patient history with little contribution from an objective measure. Previous attempts to better differentiate MD and VM have included a variety of auditory and vestibular tests, but these evaluations have demonstrated limitations or not shown the appropriate sensitivity and specificity to be used in the clinical setting. Recently, vestibular perceptual threshold testing has shown the potential to better differentiate MD and VM by demonstrating different and opposite trends with testing, and these evaluations are ongoing. In addition to vestibular evaluations, audiometry (hearing testing) is a mainstay of testing in those with vestibular symptoms, especially with any concern of MD, and is thus commonly available. Standard hearing testing, however, is not sensitive or specific enough alone to differentiate MD and VM, but this project’s hypothesis is that combining audiograms with vestibular perceptual threshold testing will result in a diagnostic power greater than that possible with either option used individually. The population of patients with MD and VM is an ideal setting to examine similarities and differences, as MD is classically an otologic disease and VM, in theory, has little to do with auditory function. Additionally, this same principal can be applied to any disease process that affects both vestibular and auditory function (such as tumors, ototoxicity).

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