Hearing Health

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.

James Dewey, Ph.D.

James Dewey, Ph.D.

University of Southern California
Filtering of otoacoustic emissions: a window onto cochlear frequency tuning

Healthy ears emit sounds that can be measured in the ear canal with a sensitive microphone. These otoacoustic emissions (OAEs) offer a noninvasive window onto the mechanical processes within the cochlea that confer typical hearing, and are commonly measured in the clinic to detect hearing loss. Nevertheless, their interpretation remains limited by uncertainties regarding how they are generated within the cochlea and how they propagate out of it. Through experiments in mice, this project will test theoretical relationships that suggest that OAEs are strongly shaped (or “filtered”) as they travel through the cochlea, and that this filtering is related to how well the ear can discriminate sounds at different frequencies. This may lead to novel, noninvasive tests of human cochlear function, and specifically frequency discrimination, which is important for understanding speech.

Noah R. Druckenbrod , Ph.D.

Noah R. Druckenbrod , Ph.D.

Harvard University
Identifying roles for contact-dependent signaling between neurons and glia during axon guidance and synaptic targeting

The mature cochlea is a spiraled hollow chamber of bone that contains all the necessary components to transmit sound information to the brain. This feat is accomplished by the precise arrangement of hair cells and spiral ganglion neurons (SGNs). This arrangement requires SGNs extend peripheral projections and establish precise synaptic connections with hair cells. What signals guide these axons through the three-dimensional terrain of the cochlea? Most studies focus on the roles of classically described axon guidance cues, which act over long distances to attract or repel axons. However, mounting evidence from recent studies and our own preliminary data lead us to hypothesize that contact-dependent signaling between SGNs and Schwann cells (SCs) are required for normal development of inner ear neural architecture and hearing. The precise role of contact-dependent interactions between SGN axons and SCs on auditory circuit formation remains unknown. This is due in part to the obstacles towards gathering high-resolution, time-lapsed information on the spatial relationships between SGNs and SCs in situ. Therefore, we will genetically label and characterize live cellular interactions between these cells in their normal, and then abnormal, physiological environment. We will measure the extent to which each of these cell types rely on each other for normal migration, differentiation, proliferation and survival. Because we have identified a mutant in which SGN-Schwann cell interaction appears disrupted, these studies will also provide insight to our understanding of Schwannoma formation. Schwannomas are Schwann cell tumors commonly found in the inner-ear and are thought to arise from a disruption in reciprocal signaling between spiral ganglion neurons (SGNs) and Schwann cells. As these tumors grow they compress afferent vestibular and auditory nerves, usually causing hearing loss, tinnitus, and dizziness. Therefore, these studies will not only contribute to our understanding of auditory circuit formation but also provide insight into what can go wrong when SGN-Schwann cell interaction is disrupted.

Brian R. Earl, Ph.D., CCCA, FAAA

Brian R. Earl, Ph.D., CCCA, FAAA

University of Cincinnati
Specifying the Integrity of Neurons in the Auditory Periphery (SiNAP)

Auditory nerve degeneration is thought to lead to difficulties with understanding speech, especially in noisy listening situations. Diagnosis of auditory nerve degeneration, however, may be missed by common hearing tests. This research examines the utility of a new technique to specify the extent and region of auditory nerve damage within the inner ear. Application of the technique in a clinical setting may help individualize hearing aids and cochlear implants, and in the future, guide delivery of therapeutic agents that can truly restore hearing to individuals with hearing loss.

Research area: Auditory physiology; Diagnostic audiology

Long-term goal of research: To develop tools for diagnosis of auditory nerve integrity that will improve the individualization of treatment options for individuals with hearing loss.

Mark Eckert, M.D.

Mark Eckert, M.D.

Medical University of South Carolina

Neural changes underlying speech-perception training in the aging brain

Many older adults with hearing loss have difficulty understanding speech in noisy environments and some feel socially isolated. Although hearing aids can improve speech understanding, hearing aid benefit may be limited if the perception of certain speech sounds has changed. Speech training programs have been shown to improve the recognition of amplified speech by older adults by focusing on re-learning cues important for perception of specific sounds. The goal of our study is to examine how the brain changes during speech training programs designed to improve speech understanding in noise. To achieve this goal, we are using MRI to examine brain activation before and after speech training and relate this activation to improvements in speech recognition. Our long term goal is to enhance the effectiveness of speech training programs by understanding the brain systems that are important for learning to hear amplified speech.

This research award is funded by the Centurions of the Deafness Research Foundation. DRF partnered with CORE Grants Program of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) to offer a one-year Centurion Clinical Research Award (CCRA) for clinical research in hearing and balance sciences.

David Ehrlich, Ph.D

David Ehrlich, Ph.D

New York University School of Medicine
Neural computations for vestibular control of movement initiation

Loss of balance and falls are common in aging populations and associated with various neurological disorders. Balance is sensed using vestibular organs in the inner ear and processed in the brainstem. However, it remains unclear how the brainstem transforms sensations of instability into corrective movements that restore balance. The objective of this project is to define how cells in the brainstem act collectively to produce rapid responses to sensations of instability. In order to measure balance responses in populations of cells located deep within the brain, this project will apply cutting-edge microscopy techniques to the zebrafish. These fish swim to remain balanced, providing a model for balance control and brainstem function in general.

Gregory I. Frolenkov, Ph.D.

Gregory I. Frolenkov, Ph.D.

University of Kentucky

Mechanoelectrical transduction without Myosin XVa

The long-term goal is to define the molecular and biophysical mechanisms shaping mechanosensitivity in cochlear hair cells. A common structural feature of hair cells in all vertebrates is the staircase arrangement of stereocilia, which is thought to be critical for mechanotransduction. This study will determine the distinguishing features of mechanotransduction in auditory hair cells of deaf shaker 2 mice that have abnormally short stereocilia due to a mutation in the motor domain of Myosin XVa.

Andy K. Groves, Ph.D.

Andy K. Groves, Ph.D.

Baylor College of Medicine
Development of Biomarkers to Study Strial Development and Degeneration

The sensory hair cells of the cochlea are able to detect sound vibrations. Hair cells need a source of potassium that helps them to convert sound energy into electrical energy that is sent to the brain. Hair cells in our cochlea are bathed in a potassium-rich fluid called endolymph, and the potassium is constantly pumped into the endolymph by a specialized group of cells in the cochlea called the stria vascularis. As humans get older, the stria vascularis can degenerate, and so the “battery” that supplies potassium to the cochlea runs down, and we lose our hearing. The goal of this project is to understand how the stria vascularis develops, and to devise ways of looking at changes in this structure with age.

Research areas: the development and regeneration of the inner ear, stria vascularis development

Long-term goal of research: We hope this knowledge may allow us to repair or slow down damage to the cochlea and lessen the effects of age-dependent hearing loss.

Kristin Hamre, Ph.D.

Kristin Hamre, Ph.D.

University of Tennessee Health Science Center

Evaluation of Stereocilia Morphology in Genotypically Math 1-null Cells in Chimeric Mice

The current time period represents an exciting one in the field of auditory functioning with the advent of stem cells and the identification of molecules that control the formation of hair cells (HCs) holding the promise of creating new HCs. One such molecule is the transcription factor Math1 that has been shown to be critical for HC generation. We have examined environmental interactions in the development of HCs and emphasize its importance in hair cell generation by showing that cells that lack Math1 can form hair cells given the correct context. However, it remains unclear whether or not these cells fully differentiate or become functional. This grant is designed to address this issue by examining the morphology of the region of the hair cell that responds to sound, the stereocilia. Analysis will determine whether this region expresses its characteristic markers in a normal manner and whether they are organized correctly. This experiment will provide useful information for further studying how the mutant HCs develop and mature in the chimeric inner ear. The use of these animals creates a system to gain further understanding of the factors that affect hair cell differentiation, knowledge essential in any corrective therapies.

Michelle L. Hastings, Ph.D.

Michelle L. Hastings, Ph.D.

Rosalind Franklin University of Medicine and Science

Therapeutic correction of Ush1c splicing in a mouse model of usher syndrome

Usher syndrome is the leading genetic cause of combined hearing and vision loss. The long-term objective of this project is to develop therapeutics for the disease. Antisense oligonucleotides (ASOs) will be used in a mouse model of Usher syndrome to correct a specific genetic defect that causes the disease. This work will demonstrate the efficacy of ASOs as a therapeutic for Usher syndrome and will also provide insights about curing the disease.

Ronna Hertzano, M.D., Ph.D.

Ronna Hertzano, M.D., Ph.D.

University of Maryland School of Medicine

A new protocol for selective and efficient sorting of the auditory sensory epithelium

The goal of this project is to develop methods for separating and characterizing the unique cell types of the auditory sensory epithelium using methods commonly used by immunologists. This could also result in the identification of new cell type-specific proteins and possibly new deafness genes.

Todd A. Hillman, M.D.

Todd A. Hillman, M.D.

Allegheny-Singer Research Institute

Otologic implant polymers for biofilm control in chronic otitis media

Chronic otitis media, including chronic serous otitis media and chronic otorrhea, is a leading cause of hearing loss in the world. This proposal will investigate the role of bacterial biofilms in chronic otitis and explore novel biofilm resistant materials for use in patients with this disease process.

Hui Hong, Ph.D.

Hui Hong, Ph.D.

Creighton University

Peripheral auditory input regulates lateral cochlear efferent system

When we think about hearing, we often picture sound traveling from the ear to the brain—a one-direction sensory pathway. However, hearing also involves a lesser-known feedback system called the auditory efferent system, which sends signals from the brain back to the ear. This system helps regulate how we hear in different sound environments and plays a protective role for the inner ear. Hearing loss is a prevalent health issue in modern society and is closely associated with other auditory disorders. Most research on hearing loss has focused on the sensory pathway. In contrast, much less is known about how the efferent system contributes to these conditions.

This project focuses on the lateral olivocochlear (LOC) neurons, the most abundant auditory efferent neurons, to understand how their function changes after noise-induced hearing loss. These changes include both the neurons’ own activity and the inputs that regulate that activity. A key question is whether the observed changes are driven directly by noise exposure or by the resulting hearing loss. To address this, we will compare LOC function following noise- induced hearing loss with that following non-noise-induced hearing loss, the latter produced by targeted ear lesions. Our approach combines whole-cell patch-clamp electrophysiology, a classic technique for recording the activity of individual neurons, with state-of-the-art optogenetics, which allows precise control and study of neuronal inputs. This research will deepen our understanding of how hearing loss impacts the auditory efferent system and help resolve inconsistencies observed in clinical studies on efferent involvement in conditions such as central auditory processing disorder, hyperacusis, and tinnitus. Ultimately, these insights will guide clinicians in refining therapeutic interventions by pinpointing dysfunctions within the brain and suggesting strategies for functional recovery. They will also help tailor treatments based on the underlying cause of hearing loss.

Mingqian Huang, Ph.D.

Mingqian Huang, Ph.D.

Massachusetts General Hospital

Expression and function of Mlf1, a candidate gene involved in both Pou4f3 and pRb pathways, in a zebrafish model

The proposed research is to understand the potential role of Mlf1 gene in hair cell development. Mlf1 has been implicated in the pathways controlled by two hair cell genes, Pou4f3 and pRb, both of which could give rise to deafness if mutated. Therefore dysfunction of Mlf1 may play a role in deafness.

Sung-Ho Huh, Ph.D.

Sung-Ho Huh, Ph.D.

Washington University
Role of FGF's in Cochlear Sensory Epithelium

Congenital sensorineural hearing loss is one of the most common hereditary disabilities, affecting 1 in 1000 children. Fgf20 null mice have congenital hearing loss associated with loss of sensory cells, and inactivation of both Fgf9 and Fgf20 result in a shortened cochlea. The goal of our research is to understand the cellular and molecular functions of Fgf9 and Fgf20 in inner ear development in vivo. The ultimate goal of this research is to learn how to direct the regeneration of malformed or damaged sensory tissue to restore or improve hearing.

Research area: hair cell regeneration

Long-term goal of research: My long term goal is to understand how Fgf signaling regulates the development, maintenance and repair of sensory hair cells and supporting cells in the cochlea. Due to lack of regenerative ability in humans after loss or dammage of hair cells, it is critical to identify signals that can reactivate developmental pathways and thus permit repair and regeneration of the damaged cochlea. Studying the mechanisms that regulate cochlear development will provide valuable clues about molecules that can be tested for regenerative activity and will thus benefit future translational studies aimed at inducing hair cell regeneration in adult humans.

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