About the Researchers

Rachael Baiduc is a hearing scientist and an Assistant Professor in the department of Speech, Language, and Hearing Sciences at the University of Colorado Boulder where she directs the Hearing Epidemiology and Research Diagnostics (HEARD) Laboratory. Her primary research interest is exploring risk factors for hearing loss especially cardiovascular disease and its antecedents. She received both her doctorate in communication sciences and disorders and her master’s degree in public health from Northwestern University in Illinois.

Melinda Anderson is an Assistant Professor at the University of Colorado School of Medicine. She is also Director of Audiology at the University of Colorado Health Hearing and Balance Clinic. Melinda’s primary research interests revolve around individuals with hearing loss and their use of hearing aids. This path of work includes clinical outcomes for users of hearing aids, the interaction between hearing aid outcomes and cognition, and the impact of age and memory status on speech perception.

About the Research

Sex Differences in the Association between Hearing Loss and Cardiovascular Disease Risk Burden
Hearing loss and cardiovascular disease (CVD) are two common chronic conditions among older adults. Research suggests that these conditions differentially affect men and women. Some individual CVD risk factors (for example, diabetes and hypertension) have been linked to hearing loss but the effect of CVD risk factors in combination has been evaluated more limitedly, particularly in the context of sex-based differences. The proposed project will examine relationships between hearing and CVD risk factors in isolation and in combination.

We will use sophisticated statistical modeling techniques (machine learning) to explore these associations using clinical data from the University of Colorado Hospital and UCHealth electronic medical records. We believe that this approach to assessing hearing outcomes may ultimately improve early identification and screening of at-risk patients, particularly those with adverse cardiometabolic risk profiles.

About the Researcher

Monita Chatterjee is an auditory scientist at Boys Town National Research Hospital where she directs the Auditory Prostheses & Perception Laboratory. She investigates the basic mechanisms underlying auditory processing by cochlear implant listeners, including studies of channel-interaction, amplitude modulation processing, modulation masking/modulation detection interference, and voice pitch coding, an area of specific deficits in listeners with cochlear implants. Chatterjee obtained her PhD in Neuroscience from Syracuse University. Her work is funded by the NIH.

About the Research

Age-Related Changes in the Perception of Emotional Speech with Cochlear Implants
Cochlear implant users’ impairment in speech emotion recognition has been linked to their quality of life, yet relatively little is known about the processes limiting their perception of spoken emotions. The findings of the proposed work will inform scientists and clinicians about basic mechanisms of speech emotion recognition, specifically the roles of prosodic and semantic cues, the effects of their degradation, and how these roles change with age-related alterations in sensitivity to these cues. The resulting information is likely to benefit the development of improved rehabilitation tools, clinical protocols, devices and processing strategies. Such improvements are urgently needed to improve social communication and quality of life in cochlear implant patients. The information will also be helpful to patients and their conversational partners, who may need to consider changing their communication style as one way to work around a fundamental limitation of the device.

About the Researcher

Allison Coffin is an Associate Professor in the department of Integrative Physiology and Neuroscience at Washington State University (WSU) Vancouver, where her lab researches sensory hair cell function and hearing preservation/loss through studying fish. She is president of the nonprofit organization Science Talk, which aims to help scientists increase the impact of their science communication through workshops and networking.

About the Research

AMPA receptor-mediated glutamate excitotoxicity and noise-induced synaptic damage
Loud noise can be fun – like when we enjoy a concert or sporting event. Loud noise can also damage our hearing, making it harder to converse with friends and family. Exposure to loud noise damages cells in our inner ears that transmit signals to the brain, and this damage can start very early, before we really recognize that we don’t hear as well as we used to. This research asks how noise damages the connection between the cells in our ears and our brains. We hypothesize that loud noise causes the nerve cells in our ears to get overly excited – and that this excess activity ultimately damages these cells and reduces the ability for these nerve cells to transmit information about the sounds around us. We use zebrafish to test this hypothesis – a small fish that has hearing cells on the outside of the body, making this fish an ideal animal to observe changes in hearing cells as they occur. Our research will provide valuable information about cellular level changes following exposure to loud noise, which will likely increase precision in therapeutic development.

About the Researcher

Michael Ghiam received his medical degree from Vanderbilt University School of Medicine, and is now a resident in Otolaryngology at the University of Miami. Given the serious impact hearing loss can have on the cognitive function of patients, Ghiam’s research has focused on the genetics of hearing loss in order to find novel therapeutic interventions in the future.

Ghiam’s mentor for this project is Simon Angeli, MD, Professor of Clinical Otolaryngology, Director of the University of Miami Ear Institute, and Neurotology Fellowship Director at the University of Miami.

About the Research

Utility of Perilymph microRNA Sampling for Identification of Active Gene Expression Pathways in Sensorineural Hearing Loss
Sensorineural hearing loss (SNHL) is the most common neurodegenerative process in humans and has been estimated to affect 360 million people worldwide. While recent advances in genetic testing has helped identify patients with genetically determined hearing loss, the genetics of acquired and progressive hearing loss (those that develop later in life) remains elusive. Recently, research on microRNAs has shown that they play essential roles in a variety of other neurological disease. Studies on animal models have shown that these micoRNAs play a key role in the development of the ear and hearing loss in animals. In our study, we want to study how microRNA expression in humans contributes to hearing loss. We will collect and characterize microRNA from patients with sensorineural hearing loss and hope that this will open novel pathways for both diagnostic and therapeutic interventions.

About the Researcher

Stefania Goncalves, MD is the first T32-Research Track Resident at the University of Miami, Miller School of Medicine. She was born and raised in Venezuela were she obtained her Medical Doctorate degree. Before starting residency, she held a Research Fellow position at the University of Miami where she took the lead on different otology-related research projects. Currently, she is a PGY3 mainly interested in the Neurotology field.  

Goncalves’s mentors Christine Dinh, MD (Surgeon Scientist) and Esperanza Bas, Pharm D, PhD. both at the University of Miami, have a broad experience in Otology and Neurotology translational research.

About the Research

Laminin-coated Cochlear Implant Electrodes can Promote Schwan Cell Dedifferentitation, Migration and Guide Neural Axon Growth In Vitro
Cochlear implants (CIs) electrically stimulate spiral ganglion neurons (SGN) and restore hearing to patients with severe-to-profound sensorineural hearing loss. However, cochlear implantation causes a local neuro-inflammatory response and scar tissue deposition that can interfere with the electrical stimulation of SGNs. By directing and enhancing SGN outgrowth towards CI electrodes, we can improve CI performance and hearing outcomes in patients.

Schwan cells (SC) are the predominant glial cells of the peripheral nervous system. SCs wrap around axons of motor and sensory neurons and produce a myelin sheath, which is important for insulation and the efficient conduction of electrical impulses along nerve fibers. Following nerve injury, myelinating
SCs enter into an active state, where they become differentiated SCs that orchestrate the regeneration of injured peripheral nerves.

This study will investigate the role of various cellular components on Schwann cell function and axon growth. We hope to improve patient outcomes by optimizing CI electrode designs to maximize SGN growth and remyelination.

About the Researcher

Cody Jeu, MD, received his medical degree from University of Texas Medical Branch at Galveston and is now a resident in Otolaryngology at the University of Illinois College of Medicine. His current research looks at the functional impact of malpositioned lower lateral cartilage in primary rhinoplasty patients.

About the Research

A cochlear implant simulation study to determine the effects of transposing frequencies on binaural benefits
Listening with two ears can help people localize sounds and understand speech in noisy environments. However, individuals with a cochlear implant (CI) in each ear, i.e., bilateral CIs, do not receive the full benefit of having two ears. Part of the reason for these reduced benefits is that bilateral CIs are independently programmed in clinics, and this programing does not account for differences in the relative locations of the CI electrodes in each ear. While this can potentially be addressed by creating individualized programs for each ear that account for differences in electrodes across ears, current approaches to do this often results in some frequencies only being presented to one ear or the other. The goal of this study is to determine if the benefits of having two ears can be preserved or improved for bilateral CI users by presenting all frequencies to both ears through new programming methods.

About the Researchers

Benjamin Johnson MD, is a resident physician in the University Hospitals Cleveland Medical Center and Case Western Reserve University’s Department of Otolaryngology-Head and Neck surgery. He studied chemical engineering at Stanford University and worked at Sandia National Laboratories (a Department of Energy Research Laboratory). He is constantly looking for ways to make an impact in his field and is excited to team up with Prof. Kumar Alagramam and members of his hearing research group to help continue working on novel drug development, like using anti-malarial Artesunate to treat a rare but progressive from of hearing loss, Usher Syndrome type 3A.

About the Research

Antimalarial Artesunate as a Novel Treatment to Mitigate Hearing Loss Associated with Usher Syndrome Type IIIA
Usher Syndrome type 3A (USH3A) is a genetic disorder that results in post-lingual progressive loss of vision and hearing. On average 1.2 out of every 100,000 people are affected by this disorder. The underlying cause is a mutation in a gene called clarin1 which is responsible for making a protein that is essential for the function of hair cells – sensory cells in our inner ear critical for balance and hearing. No treatment is available to stop or slow the progression of vision or hearing loss in USH3A.

To understand the genetics behind Usher syndrome and to create a platform to test new drugs and therapies, our laboratory created a mouse model that mimics the progression of hearing loss associated with the clarin1-N48K mutation, the most common USH3A causative mutation in both North America and among those of Ashkenazi Jewish descent. Affected mice have the same defect in the clarin1 gene as humans and produce a defective version of the clarin1 protein that largely fail to sort to its designated ‘zip code’ in the cell, namely the cell surface. The cell surface localization of the clarin1 protein is necessary for the hair cells to function normally. Testing showed mice that harbor the clarin1-N48K mutation develop hearing but fail to retain that function, similar to the USH3A patients with that mutation. Available evidence led to the hypothesis that attenuation of hearing loss could be achieved if the levels of the mutant clarin1 protein reaching the cell surface could be enhanced with a drug or other agents. A review of the literature and preliminary work in our lab pointed to the antimalarial drug, Artesunate, as a good candidate to test our hypothesis.

Previous work demonstrated that the clarin1 protein localizes to the cell surface, but the clarin1-N48K version of the protein is largely ‘stuck’ in the endoplasmic reticulum, a part of a cell where proteins are synthesized and processed before it is sorted to the cell surface. Also, previous work showed that artesunate could liberate ER-bound clarin1-N48K protein and restore hair cell function in a zebrafish model of USH3A. In the proposed work, the efficacy of artesunate to mitigate hearing loss in a mammalian model of clarin1-N48K USH3A will be tested.

About the Researcher

Matthew Maksimoski received his medical degree from the University of Cincinnati College of Medicine and is now a resident in Otolaryngology – Head and Neck Surgery at Northwestern University Feinberg School of Medicine.

About the Research

Long term outcomes from gamma knife treatment for vestibulocochlear nerve schwannomas in a large, tertiary care, academic hospital

Vestibular schwannomas represent a non-cancerous growth of a nerve which contributes to balance. These masses frequently enlarge and cause hearing loss in patients afflicted with this disease. Surgery, observation, and radiation are all options for treatment. Traditionally, radiation has been proposed as safe for hearing, with less risks than surgery or watchful waiting, but as we learn more about radiation and its risks, this has been called into question. Previous studies have examined the short term (under 5 year) effects of stereotactic radiosurgery on the vestibulocochlear system following this procedure. 

Northwestern’s Otolaryngology Department has a 20+ year history of patients who have been treated for vestibular schwannomas with radiation, and with this wide-reaching population, we are searching for answers as to whether in the long term radiation really does preserve hearing, or if there are hidden downstream effects that may not be known. We hope, with a population of hundreds of patients, to be able to shed some light on the potential long-term hearing effects of this radiation treatment, and to give patients the most accurate and helpful guidance we can.

About the Researcher

Dhasakumar Navaratnam MD, PhD is a neurotologist and neurologist who provides advanced comprehensive evaluation and treatment for patients with hearing and balance problems. He received his MD from the University of Colombo and his PhD from the University of Oxford. He completed his residency in neurology and post-doctoral training in hearing research at the University of Pennsylvania, Philadelphia, PA. Dr. Navaratnam is funded by the NIH and performs basic science research on aspects of hearing and balance, and regeneration in the auditory and vestibular systems.

About the Research

Defining the molecular and cellular basis of Meniere’s disease using single cell RNA sequencing
This proposal seeks to identify the molecular and cellular events underlying Meniere’s disease (MD) using single cell RNA sequencing of inner ear tissue from patients with the disease.

The use of SCRNA seq will allow us to make an unbiased assessment of the pathophysiology of Meniere’s disease using tissue from patients with Meniere’s disease. There are many confounding theories on its causation. Our underlying hypotheses is that immunological mechanisms, and disordered salt and water exchange play a significant part in the evolution of the disease. In experiments with
adult mouse inner ears, we have identified three populations of macrophages and several populations of lymphocytes. We believe these cells play a significant part in disease evolution and causation.

About the Researchers

Habib Rizk, MD, is an Assistant Professor of Otology-Neurotology in the Department of Otolaryngology- Head & Neck Surgery at the Medical University of South Carolina. He serves as director of the vestibular program and chairs the Clinical and Translational Research Ethics Consultation Service. He is on the board of directors of the American Balance Society, and a member of the Equilibrium Committee of the American Academy of Otolaryngology – Head & Neck Surgery. His academic and clinical interests pertain to all areas of otology and neurotology with a specific focus on medical and surgical management of vestibular disorders.

Yaun Fang Liu, MD, and Shaun A. Nguyen, MD, FAPCR. are co-investigators on this project.

About the Research

Assessing the Efficacy of a Serotonin and Norepinephrine Reuptake Inhibitor for Improving Meniere’s Disease Outcomes
Meniere’s disease is a major cause of vertigo, affecting around 190 people per 100,000 in the US. As of yet, the cause of Meniere’s disease is uncertain and there is no gold-standard treatment. Given the lack of high-level evidence for current medications (diuretics, betahistine, steroid injections), we want to compare the efficacy of oral, daily venlafaxine to placebo as a new treatment for Meniere’s disease. Venlafaxine is a serotonin and norepinephrine reuptake inhibitor (SNRI) which is well-tolerated in the treatment of depression and anxiety. There is evidence that serotonin can modulate balance function in vestibular nuclei, the inferior olive, and the cerebellum. Norepinephrine has also been shown to inhibit activity in vestibular nuclei. Furthermore, venlafaxine can reduce vasopressin receptor activation, which changes inner ear pressure by reducing the endolymphatic hydrops (swelling of the fluid spaces of the inner ear that is correlated to symptoms of Meniere’s disease). This trial will take place in a multidisciplinary, neurotology clinic. We will compare changes in patient-reported symptoms using quality-of-life questionnaires. Our findings may introduce venlafaxine as a potential therapy that could benefit many patients suffering from Meniere’s disease.

About the Researcher

Tal Teitz, PhD, is an Assistant Professor of Pharmacology in the Pharmacology and Neuroscience department within the School of Medicine at Creighton University. She received her graduate degree in Biochemistry under the mentorship of Dr. Dan Canaani at the Tel Aviv University. She continued post doc training with Dr. Yuet Wai Kan at the UCSF Medical School at San Francisco and continued her work at Memorial Sloan Kettering Hospital in NYC. She joined St. Jude Children’s Research Hospital, Memphis Tenn., in 1998, where she worked on neuroblastoma and molecular mechanisms of cell death in childhood tumors. In 2012, she joined Dr. Jian Zuo’s group at St. Jude Children’s Hospital to develop studies on drug therapy for hearing loss. Dr. Teitz joined the faculty at Creighton University in April 2018, where she is currently building a research group to identify and develop drugs for prevention of hearing loss.

About the Research

Repurposing an FDA Approved Drug Dabrafenib for Protection from Noise-induced Hearing Loss
Hearing loss caused by noise exposure and aging is a major unmet medical need in our society, affecting over 600 million people worldwide. To date, no drugs have been approved by the FDA to treat hearing loss and development of a drug to treat the condition would be a significant contribution to human health. We recently conducted screens of large number of compounds (above 4,500 compounds) for cisplatin-induced cell-death protection in an inner ear cell line and identified a top candidate compound dabrafenib (TAFINLAR). The drug is orally bioavailable, and FDA approved for treatment in humans against several cancers. Dabrafenib protected mouse cochlear explants against hair cell death induced by cisplatin, protected in mice by oral delivery against cisplatin-induced hearing loss and best protective effects were demonstrated against noise- induced hearing loss. Thus, we aim to rapidly repurpose dabrafenib for oral delivery to humans to protect from noise-induced hearing loss. In this study, we will test in mice different regimens of drug administration and various noise levels to optimize the drug dabrafenib for clinical studies in humans. We are deeply grateful to the American Hearing Research Foundation for supporting us in achieving this aim. Our studies will hopefully provide one of the first FDA approved drugs repurposed specifically for hearing protection.

About the Researcher

Dr. Zheng is an Associate Professor in the Department of Otolaryngology-Head and Neck Surgery, Feinberg School of Medicine of Northwestern University. She also holds joint appointments in the Department of Communication Sciences and Disorders at Northwestern University. Dr. Zheng is a Fellow of the Hugh Knowles Center for Hearing Research. She received her Ph. D degree from Michigan State University. The long-term goal of Zheng’s lab is to identify and investigate molecules that play important roles on the auditory and vestibular systems, and to further develop a better strategy to prevent hearing loss and vestibular disorders.

About the Research

Investigating functions of a cilium protein in vestibular system
Vestibular disorders are important public health problems resulting in substantial economic and societal costs. In fact, 69 million Americans suffer some form of vestibular dysfunction. However, effective treatments are difficult as the etiologies of these disorders remain largely enigmatic.

Cilia are microtubule (MT)-based surface projections that play vital roles in various tissues and cells. In our body, there are two major types of cilia: motile cilia and non-motile, sensory cilia. The majority of motile cilia are composed of MTs in the ‘9+2’ configuration, i.e., 2 central singlet MTs surrounded by 9 doublet MTs. In contrast, most of sensory cilia do not have the central MT pairs. However, unlike most sensory cilia, sensory cilia on vestibular hair cells have the central MT pair, similar to the motile cilia. It is known that the central MT singlet pair in motile cilia is required for the synchronized back-and-forth planar motion but why non-motile vestibular sensory cilia also have a ‘9+2’ configuration remains unclear. We have discovered that CAMSAP3 proteins are required for the formation of the central singlet MTs for motile cilia. Therefore, we hypothesize that CAMSAP3 is also crucial for the formation of normal vestibular sensory cilia, which are critical to transmit signals of head position/movements to the brain. To test our hypothesis, we will investigate the role of CAMSAP3 using a conditional knockout mouse model specific to the inner ear. Different techniques including confocal microscopy, transmission electron microscopy, and scanning electron microscopy will be used to test our hypothesis. The data obtained from the proposed experiments will provide new scientific knowledge fundamental to the basic biology regarding ciliogenesis and ciliary function as well as help us to understand the pathologies underlying vestibular disorders.