Elizabeth Bryda, Ph.D.

Elizabeth Bryda, Ph.D.

University of Missouri–Columbia

Role of otocadherin and CAML in the inner ear

By exploring the underlying biological pathways involved in normal as well as abnormal hearing and balance, a more targeted approach to treatment is possible. By exploring the relationship between otocadherin and CAML, increased knowledge of the role of otocadherin, including which proteins it interacts with, will enable researchers to determine if it will be possible to correct defects in patients with Usher syndrome.

Brad Buran, Ph.D.

Brad Buran, Ph.D.

Oregon Health & Science University
Neural mechanisms of hyperacusis in the inferior colliculus and cortex of ferrets with noise-induced auditory neurodegeneration

The development of effective treatments for hyperacusis (the diminished tolerance of loud sounds) and tinnitus (a persistent ringing in the ears) is limited by existing animal models. Current animal models are generated by high-intensity noise exposure or by the administration of salicylate, the active ingredient in aspirin. In addition to producing symptoms of hyperacusis and tinnitus, both of these manipulations lead to elevated hearing thresholds by damaging inner ear sensory cells. Damage to inner ear sensory cells leads to altered auditory processing, which makes it difficult to identify the specific changes that produce hyperacusis and tinnitus. While hearing loss is the primary risk factor for these disorders, they cannot be explained by damage to sensory cells alone. In fact, hyperacusis, tinnitus, and difficulty understanding speech in noise have been reported even in individuals with normal auditory thresholds. Therefore, in order to tease out the specific changes to the auditory system that result in tinnitus and hyperacusis, the ideal animal model should not have sensory cell damage.

Recent evidence from studies in mice suggests that moderate noise exposure can cause damage to the auditory nerve without altering hearing thresholds. Mice with this type of auditory nerve damage show symptoms of hyperacusis and humans who report tinnitus, but have normal auditory thresholds, also show signs of similar damage. It has also been hypothesized that auditory nerve damage will lead to increased difficulty understanding speech in the presence of background noise. Thus, moderate noise exposure provides a potential animal model for patients who have normal hearing thresholds, yet still experience hyperacusis, tinnitus, or difficulty hearing in noise. We will assess the perceptual effects of this auditory nerve damage by training noise-exposed ferrets to perform behavioral tests designed to parallel tests of hyperacusis, tinnitus, and difficulty hearing in noise that are conventionally used in human listeners. We will also assess how auditory responses in the central auditory system are altered by this type of auditory deficit to determine whether the changes in neural responses may explain the perceptual effects of hyperacusis, tinnitus, and difficulty hearing in noise.

R. Michael Burger, Ph.D.

R. Michael Burger, Ph.D.

Lehigh University

Efferent loizounction in sound localization processing

Auditory processing relies on precise coding of acoustic features to build an accurate internal representation of the environment. Sensory systems build this representation through faithful encoding of sensory stimuli at the level of sensory organs. This neural signaling is enhanced by active feedback on sensory neurons from higher central processing centers. These "efferent" pathways have been characterized for the cochlea and to some extent, in the midbrain. There is little data efferent function in the early stages of auditory processing in structures that process sound location information. This may be due, in part, to the complexity of this system in mammalian circuits. The bird auditory system is a major model for human sound localization processing. Indeed, birds process ascending circuitry that is strikingly similar to mammals in structure and function, but with efferent circuitry that is appealingly simple. My aim is to investigate this elegant efferent brain stem circuit in birds to build a comprehensive model of its function within this functionally understood auditory circuit. These studies will both characterize the neurons responsible for this feedback, and examine their impact on their targets. The long-term objective is to build a mechanistic understanding of sound localization circuitry in vertebrate systems.

George Burwood, Ph.D.

George Burwood, Ph.D.

Oregon Health & Science University

Apical cochlear mechanics after cochlear implantation

The long-term research goal is to establish, treat, and prevent cochlear implantation-induced hearing loss. This mechanics project is the first time the vibration of the inner ear has been measured in the presence of a cochlear implant, and there is much to discover—such as measuring the efficacy of drugs that help to suppress scarring, as well as testing different electrode designs, and even extending to other diseases of the inner ear such as Ménière’s disease. I believe that optical coherence tomography has a big role to play in the future of both basic hearing science and hearing restoration.

Irina Calin-Jageman, Ph.D.

Irina Calin-Jageman, Ph.D.

Emory University

Harmonin interactions with voltage-gated Ca3+ channels in a mouse model of Usher syndrome

Usher syndrome is the leading cause of hereditary deafness and combined deafness and blindness in humans. This research will illuminate a novel mechanism of Ca3+ channel regulation that may be important for auditory function. By carefully characterizing the defects in Ca3+ channel properties in the mouse Usher syndrome model, the researcher will be able to follow-up with strategies to restore function to these mice, which may be ultimately useful in limiting deafness and balance problems in human patients of Usher syndrome.

Julia Campbell, Ph.D., Au.D.

Julia Campbell, Ph.D., Au.D.

University of Texas at Austin
Auditory gating in tinnitus

Tinnitus is the perception of sound, such as ringing or buzzing, without an external source. Though tinnitus likely arises, in part, from hearing loss in the inner ear, research has determined that the ongoing perception of tinnitus occurs in the brain. It has been suggested that auditory gating, a function carried out by the brain in filtering out unimportant auditory information, may be abnormal in individuals with tinnitus and contribute to the conscious perception of the phantom sound.

Auditory gating can be measured noninvasively through the brain’s cortical response to sound during recording of brainwave activity, known as EEG (electroencephalography). In typical auditory gating function, cortical auditory evoked potentials (CAEPs) recorded during EEG show a decrease in amplitude when sounds (e.g., tone pairs) are presented close together in time. This decrease in amplitude reflects the brain’s ability to filter out repetitive auditory input. In atypical gating function, CAEP amplitude remains the same across sound presentation or shows little change, again suggestive of the brain’s inability to filter out irrelevant input.

This study aims to evaluate auditory gating processes in tinnitus, including cortical sources of active gating networks as observed through source localization analyses. These results will be correlated with subject reports of tinnitus severity.

Wei-Min Chen, Ph.D.

Wei-Min Chen, 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 areas: otitis media, genetics

Long-term goal of research: Findings from our research are expected to improve the clinical prevention of chronic infections; therefore decreasing pediatric antibiotic use, surgery, and deafness.

Renjie Chai, Ph.D.

Renjie Chai, Ph.D.

Stanford University
Characterization of Wnt-responsive progenitor cells in the mammalian cochlea

Hearing loss is a common sensory disorder affecting nearly 50 million adults in the United States alone. The majority of hearing loss is caused by the loss of the inner ear sensory hair cells, which, in mammals, lack the ability to regenerate. In this proposal, we will gain insights into the regenerative potential of the mammalian cochlear hair cells, with long term goal to improve the current treatment of hearing loss via hair cell regeneration. The Wnt signaling pathway has been found to play a crucial role in maintaining the stem cell population in several organ systems. Recently our laboratory has found a transient expression of active wnt signals in the mouse cochlea, and found 2 inner ear progenitor cell populations marked by two Wnt downstream target genes. This project has been designed to systematically investigate the role of the Wnt pathway in maintaining these two Wnt responsive progenitor cell populations.

Research area: hair cell regeneration

Long-term goal of research: To use hair cell regeneration and cell-base therapy to treat patients with sensorineural hearing loss.

Divya Chari, M.D.

Divya Chari, M.D.

Mass Eye and Ear

Auditory and vestibular phenotype characterization of a Ménière’s disease model in humans and mice with X-linked hypophosphatemia

Our group has begun to segregate the pool of Ménière’s disease patients into distinct subtypes based upon specific clinical characteristics and morphologic features of the inner ear endolymphatic sac and vestibular aqueduct. One cohort—designated MDhp—demonstrated on histopathology and radiologic imaging an incompletely developed (hypoplastic) endolymphatic sac and vestibular aqueduct and had a high comorbid prevalence of X-linked hypophosphatemia. XLH is a genetic phosphate metabolism and bone growth disorder caused by a loss-of-function variant in the Phex gene. The high coincidence of XLH in the MDhp cohort led to the hypothesis that the two disorders may have etiologic similarities. Our preliminary studies suggest that the Phex gene-deficient XLH mouse also recapitulates clinical features of the MDhp cohort: hearing loss and balance dysfunction, endolymphatic hydrops, and hypoplasia of the endolymphatic sac and vestibular aqueduct. During this project we will determine whether the inner ear phenotype of humans with XLH generally resembles that of MDhp, and whether the XLH mouse model also exhibits an MDhp phenotype. Characterizing the MDhp phenotype within the context of patients with XLH and a Phex-deficient mouse model is a critical first step toward investigating the pathophysiology of MD and elucidating the genetic etiology of the MDhp subgroup. This research may demonstrate that the Phex gene-deficient mouse can be used as a reliable animal model of the MDhp subtype, which will pave the way for future studies of the role of the Phex gene mutation in MD patients and, more generally, the genetic basis of this complex disease. 

Soyoun Cho, Ph.D.

Soyoun Cho, Ph.D.

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

Inyong Choi, Ph.D.

Inyong Choi, Ph.D.

University of Iowa
Neural correlates of selective listening deficits in a multiple-speaker environment

Choi’s lab studies how human brains understand speech in noisy everyday settings, how central brain functions are affected by hearing loss, and how we can improve hearing-related brain functions with training.

This study will investigate several key neural processing systems required for successful speech communication in noisy social settings, and how neural processing deteriorates in listeners with degraded hearing ability. As such the project involves basic neuroscientific research of the central auditory system and translational research on hearing rehabilitation techniques.

Yoojin Chung, Ph.D.

Yoojin Chung, Ph.D.

Massachusetts Eye and Ear Infirmary
Restoring binaural hearing with cochlear implants in early-onset deafness

Many profoundly deaf people wearing cochlear implants still face challenges in everyday situations such as understanding conversations in crowds. This is because, even with cochlear implants in both ears, they have difficulty making full use of subtle differences in the sounds reaching two ears to identify where the sound is coming from. This problem is especially acute in children with congenital deafness. We will study how perceptual training can help the brain to develop the circuitry for processing this precise information in animals with early-onset deafness. Results from the study will eventually lead to new sound processors and rehabilitation strategies specifically adapted for bilateral cochlear implants.

Research area: neural coding of cochlear implant stimulation, central auditory plasticity

Long-term goal of research: To improve treatments for children with early-onset deafness by studying how neural mechanisms for binaural processing are altered by auditory deprivation during development and whether these effects can be reversed by CI stimulation.

Donald E. Coling, Ph.D.

Donald E. Coling, Ph.D.

Proteomic investigation of cisplatin-induced ototoxicity

Cisplatin is one of the most frequently used chemotherapeutic agents. However, side effects of hearing loss and kidney failure limits its clinical use. More than 50 percent of patients treated with cisplatin suffer cochlear hair cell death. Identification of proteins whose degradation or synthesis is induced by cisplatin is expected to lead to new methods of clinical intervention to reduce negative side effects.

Brenton Cooper, Ph.D.

Brenton Cooper, Ph.D.

Texas Christian University
Lateralization of acoustic perception in Bengalese finches

Cooper’s research aims to further our understanding of how different sides of the brain are specialized for processing different frequencies of sounds. Auditory processing of speech and language is lateralized to the left hemisphere of the human brain. Cooper’s specific aims are to determine whether auditory processing in the Bengalese finch is lateralized to specific sides of the brain, as in humans, and to determine whether the lateralization is learned or genetically determined.

Research area: Central Auditory Processing Disorder

Long-term goal of research: To develop this animal model for testing and refining treatments for hearing loss and lateralized frequency processing deficits in humans, including CAPD.

James M. Coticchia, M.D.

James M. Coticchia, M.D.

Wayne State University School of Medicine

Nasopharyngeal biofilms in the pathogenesis of recurrent acute otitis media

Ear infections are a significant problem in infants and children. Research has shown bacteria that cause ear infections are resistant to antibiotics. By understanding which bacteria form these chronic infections and by evaluating new treatments we hope to reduce the number of children that require ear tubes. This will allow researchers to understand which bacteria form biofilms; when biofilms develop and help to better understand the role of biofilms in recurrent ear infections; and new treatment options for children with frequent ear infections.

Scott Cronin, M.D.

Scott Cronin, M.D.

University of Michigan
Ototoxicity of a common drug delivery tool and FDA Orphan Drug, 2-hydroxypropyl-beta-cyclodextrin

Cyclodextrins are a class of molecules that can dissolve cholesterol and other lipids in the body. They are commonly found in household cleaning products, and they are being studied in the treatment of Niemann-Pick disease. Unfortunately, cyclodextrins cause hearing loss and damage to the cochlea at high doses. This project will study the effects of 2-hydroxypropyl-betacyclodextrin (HPBCD) on hearing in a mouse model by injecting this drug under the skin and into the brain. This research will quantify the level of hearing loss and cochlear damage caused by this medication. In addition, the mechanisms of hearing loss and ototoxicity through a variety of techniques will be studied. This novel approach to studying HPBCD may have powerful impacts for patients with Niemann-Pick disease as well as advance our understanding of drug related ototoxicity.

Research area: Hearing loss; Ototoxicity

Long term goal of research: To develop novel tools for both the prevention and treatment of hearing loss. Cyclodextrins are powerful drugs that can be used to deliver a variety of drugs into the eye, brain, and even the ear. They can also be used to treat lysosomal storage disorders such as Niemann-Pick disease. Unfortunately, at high doses they cause hearing loss and damage the cochlea. The long-term objective is to understand the mechanisms of cyclodextrin induced hearing loss. Hopefully this will lead to novel strategies to ameliorate cyclodextrin damage while retaining its drug-delivery and therapeutic advantages. In addition, new therapeutic uses for HPBCD to treat inner ear disorders will be developed.

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Margaret Cychosz, Ph.D.

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Margaret Cychosz, Ph.D.

University of California, Los Angeles
Leveraging automatic speech recognition algorithms to understand how the home listening environment impacts spoken language development among infants with cochlear implants

To develop spoken language, infants must rapidly process thousands of words spoken by caregivers around them each day. This is a daunting task, even for typical hearing infants. It is even harder for infants with cochlear implants as electrical hearing compromises many critical cues for speech perception and language development. The challenges that infants with cochlear implants face have long-term consequences: Starting in early childhood, cochlear implant users perform 1-2 standard deviations below peers with typical hearing on nearly every measure of speech, language, and literacy. My lab investigates how children with hearing loss develop spoken language despite the degraded speech signal that they hear and learn language from. This project addresses the urgent need to identify predictors of speech-language development for pediatric cochlear implant users in infancy.

Alain Dabdoub, Ph.D.

Alain Dabdoub, Ph.D.

University of California San Diego

Canonical wnt signaling in the developing organ of corti

Within the organ of Corti, a single row of inner hair cells and three rows of outer hair cells extend along the basal- to-apical axis of the cochlea. Every sensory hair cell is separated from the next by an intervening non- sensory supporting cell, resulting in an invariant and alternating mosaic. The importance of the formation of this structure is illustrated by the significant auditory deficits in animals with patterning defects in the cochlear duct. Since the perception of sound is based on the integrity and function of this strict cellular organization, it is important to elucidate the developmental processes responsible for generating and regulating this pattern. The development of the cochlea and the organ of Corti requires several events including growth, specification of cell fates, proliferation and differentiation. In many systems the Wnt/_-catenin pathway plays a crucial role in determining cell fate, growth and proliferation. We have data indicating that several Wnt signaling genes are expressed in the cochlea. Furthermore, our preliminary results demonstrate that activating the Wnt/_-catenin pathway in whole organ cochlear explant cultures results in a robust increase in the size of the prosensory domain that gives rise to the organ of Corti and increases in auditory hair cells.

Evelyn Davies-Venn, Au.D., Ph.D

Evelyn Davies-Venn, Au.D., Ph.D

University of Minnesota
Behavioral and neural correlates of amplification outcome

Understanding individual factors, beyond hearing thresholds, that account for the high variability in success in the use of hearing aids is an important question with immediate clinical implications. This project aims to evaluate how fundamental aspects of auditory processing interact with high-intensity sounds and influence hearing aid amplification outcomes. Behavioral and speech and non-speech measures will be used to determine how spectral auditory processing interacts with high intensity sounds and influences amplification. This will help us determine factors that contribute to diminished speech perception in noisy environments for individuals with hearing loss and how their perception of amplified speech can be enhanced in noisy environments.

Michael R. Deans, Ph.D.

Michael R. Deans, Ph.D.

Harvard Medical School

Genetic dissection of planar cell polarity within the inner ear

It is broadly accepted that hearing and balance requires the correct orientation of hair cells and their stereocilia bundles within the inner ear. This patterning is called planar cell polarity and involves the coordinated organization of adjacent hair cells. This project aims to understand the developmental mechanisms generating planar polarization and to determine the effects of hair cell disorganization upon auditory and vestibular function.

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