General Hearing Health

Dunia Abdul-Aziz, M.D.

Dunia Abdul-Aziz, M.D.

Mass Eye and Ear, Harvard Medical School
Targeting epigenetics to restore hair cells

Most commonly, deafness is due to loss of cochlear sensory hair cells, which can occur because of genetic diseases, loud noise, certain drugs, or aging, and it can also result in the development of sometimes disabling ringing in the ear (tinnitus) and sound sensitivity (hyperacusis). Balance disorders similarly arise from loss of respective sensory hair cells in the inner ear vestibular organ. Treatments aimed at reversing hearing loss by stimulating the recovery of hair cells are greatly needed. The death of these hair cells in the ear is permanent because the inner ear loses its ability to replenish lost cells once it has matured, which occurs shortly after birth in mice and in the fetus in humans. To reestablish this potential and to recover lost hair cells, this project uses a novel technology to reprogram stem cells from the inner ear to turn into hair cells. This has pointed to a new candidate drug target, lysine-specific demethylase 1 (Lsd1), an epigenetic regulator that appears to be at least partly responsible for this loss of regenerative capacity. By targeting Lsd1, this project will study its role in the formation of hair cells and investigate its potential as a drug target for treatment of hearing loss.

Tamara Alliston, Ph.D.

Tamara Alliston, Ph.D.

University of California San Francisco

The role of cochlear capsule bone remodeling in hearing loss

Although several bone diseases cause sensorineural hearing loss, the mechanism by which bony defects impair auditory function remains unclear. The long term goal of this research is to better understand the role of bone in the sensorineural function of the ear—with the objective of identifying bone targets that might be therapeutically effective in the prevention or reversal of hearing loss. The goal of this proposal is to test the hypothesis that abnormal remodeling of the cochlear capsule results in hearing loss by damaging the material quality of the cochlear bone matrix. Our recent studies on bone disease-associated hearing loss have shown that cochlear bone hardness is critical for hearing. Understanding bisphosphonate action in the ear is clinically important because drugs are commonly used to treat osteoporosis and bone disease-associated hearing loss.

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Pierre Apostolides, Ph.D.

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Pierre Apostolides, Ph.D.

University of Michigan
Novel mechanisms of cortical neuromodulation

Although there is currently no cure for tinnitus, recent experimental studies propose vagus nerve stimulation (VNS) may be a potential treatment to mitigate the condition because VNS releases natural chemicals (neuromodulators) that increase the brain’s ability to change. This is interesting because VNS has previously received Food and Drug Administration approval for treating drug-resistant epilepsy and treatment-resistant major depressive disorder. Despite considerable interest, how neuromodulators released by VNS could be therapeutically useful for tinnitus is unknown. This project will employ cutting-edge techniques to test a novel hypothesis: A major mechanism of action for neuromodulators is that they affect the function of dendrites, the long cable-like structures upon which neurons receive and integrate electrical signals. By identifying how neuromodulators impact the function of dendrites, these experiments may uncover novel targets for developing new treatments for tinnitus.

Franziska Auer, Ph.D.

Franziska Auer, Ph.D.

New York University

Defining myelin’s role in developing vestibular circuits

The vestibular system serves a vital purpose, to stabilize posture and gaze by producing corrective head and body movements. Vestibular circuits are myelinated early in life, suggesting a crucial role in proper balance development. In addition, balance, posture, and gait deficits are common symptoms for patients affected by diseases where myelin breaks down. Myelination alters conduction velocity thus it is crucial for circuit function. Recent studies have shown that the formation of novel myelin plays an essential role in memory formation and learning. The overall goal of this project is to define a role for myelin in vestibular circuit development and postural behaviors. We will investigate the consequences of loss of vestibular myelin on postural development. The work will also establish and validate transformative new tools to selectively disrupt the myelination of genetically defined subsets of neurons. I will test the role of myelin in different circuits for postural behavior, locomotion, and coordination in order to understand myelin’s contributions to circuit function. These novel tools will also permit future investigations into the role of myelin in auditory circuits and the consequences for hearing health.

Rajeshwar Awatramani, Ph.D.

Rajeshwar Awatramani, Ph.D.

Northwestern University

Conditional genetic manipulations at molecular intersection points to identify the embryonic origin of brainstem auditory neurons

Essential to typical sound recognition is the proper development of the auditory processing centers in the brainstem. Auditory information from the inner ear coalesces in a tonotopic distribution upon the brainstem cochlear nuclei. Utilizing a newly developed intersectional genetic fate mapping approach, the aim of this research project is to decipher genetic programs underlying the formation of these auditory nuclei.

Rachael R. Baiduc, Ph.D., MPH

Rachael R. Baiduc, Ph.D., MPH

University of Colorado Boulder
Hearing loss and cardiovascular disease risk burden: epidemiological and physiological data

Although hearing loss is often considered in isolation, recent evidence points toward comorbidity with other conditions including cardiovascular disease (CVD). Both hearing loss and CVD are prevalent chronic conditions, and the auditory system has a demonstrated vulnerability to cardiovascular-related diseases. Given that audiologists are likely to see patients with co-occurring conditions, a better understanding of CVD risk factors is useful. This study will use, for the first time, the notion of risk burden to explore the link between CVD and hearing loss in a large dataset, and will examine the link using specific measures of auditory status in a cross-sectional study. Through the use of cost-effective, clinically available techniques in conjunction with epidemiological data, a greater understanding of CVD risk factors that contribute to hearing loss will be a key toward prevention, early identification, and treatment.

Renee Banakis Hartl, M.D., Au.D.

Renee Banakis Hartl, M.D., Au.D.

University of Colorado, Denver
Effect of deafness duration on the efficacy of cochlear implants for single-sided deafness

One of the large challenges in attempting to predict outcomes of cochlear implantation is due to the diverse clinical characteristics of implant candidates. Our initial studies have worked to isolate the effect of one variable (duration of deafness) in a specific etiology (single-sided deafness) on implant efficacy. By studying auditory neurophysiological responses to cochlear implant stimulation in an animal model for single-sided deafness, we can investigate objective performance and changes in brainstem physiology.

Francisco Barros-Becker, Ph.D.

Francisco Barros-Becker, Ph.D.

University of Washington

Aminoglycoside compartmentalization and its role in hair cell death

The goals for this project are to develop new tools that will help the scientific community to deepen our understanding of the vesicular network in hair cells, both during stress and normal conditions. We will develop novel fluorescent probes to mark the different compartments in the vesicular network. This will allow for visualization of the drug as it transitions through various levels within the vesicular network. In order to better analyze these structures, we will pair these images with custom-made image analysis algorithms that will allow us to study vesicles in a deeper way. Overall, these tools will allow us to open new research avenues that will help to further understand how aminoglycosides, and other drugs with ototoxic effects, like cisplatin, a cancer chemotherapy drug, are killing hair cells. Our results could help direct new research and lead to novel therapeutic treatments to avoid further hearing loss in patients undergoing these treatments.

Gregory J. Basura, M.D., Ph.D.

Gregory J. Basura, M.D., Ph.D.

University of North Carolina at Chapel Hill

Synaptic organization and plasticity in the auditory cortex following cochlear ablation: role of serotonin neurotransmission

The long-term objective of this proposal is to investigate mechanisms of plasticity in auditory cortex neurons following bilateral cochlear ablation. The evaluation of auditory cortex neuronal functioning in an animal model of deafness and the progressive identification of neurotransmitter receptor systems that may modulate their activity after hearing loss, may lead to the development of pharmacologic tools to facilitate restorative hearing.

Dwight E. Bergles, Ph.D.

Dwight E. Bergles, Ph.D.

Johns Hopkins University

Connexin involvement in spontaneous activity in the developing cochlea

Our recent studies indicate that spontaneous activity in the developing auditory nerve is initiated by the release of ATP from supporting cells in the organ of Corti. The goal of these studies is to evaluate the role of connexins in triggering ATP release from supporting cells. We propose to use electrophysiological and imaging methods in whole-mount preparations of pre-hearing cochleas to probe the sensitivity of spontaneous activity to manipulations that inhibit gap junction/hemichannel activity. We will extend these studies by testing whether expression of connexin 26 mutants associated with congenital hearing loss (R75W, W44C) alters this spontaneous activity. The studies outlined in this proposal seek to test the hypothesis that connexins play an essential role in the propagation of Ca2+ waves through the support cell network, and are responsible for the release of ATP in the developing organ of Corti.

Keith Bryan, Ph.D.

Keith Bryan, Ph.D.

University of Iowa
Investigating the Role of CaBP1 in KCNQ4 Channel Modulation

KCNQ4 potassium channels play an important role in controlling the responsiveness of auditory hair cells to sound stimulation. Mutation of the gene encoding this channel cause deafness in humans, which is typically due to improper functioning of these channels in the ear. I have identified a novel interaction between Ca2+ binding protein 1 (CaBP1), which is highly expressed in auditory hair cells, and KCNQ4. The goal of this research is to evaluate the functional consequences of this interaction on the cellular localization and biophysical properties of KCNQ4 channels in auditory hair cells.

Research area: fundamental auditory research

Long-term goal of research: To understand at the molecular level how hair cells function normally in sound detection and develop novel therapeutic strategies for treating patients with inherited forms of hearing loss.

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.

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.

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.

Soyoun Cho, Ph.D.

Soyoun Cho, Ph.D.

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

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.

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.

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