Research Presenting the 2023 First-Year Emerging Research Grants Scientists.

Presenting the 2023 First-Year Emerging Research Grants Scientists

Through the Emerging Research Grants (ERG) program, Hearing Health Foundation (HHF) provides seed money to scientists working across the entire spectrum of hearing and balance research, including many underfunded areas. Since 1958, ERG grants have played a foundational role in the careers of many academic researchers and clinicians in hearing and balance fields.

The competitive ERG program awards grants to only the most promising investigators. Recipients are exceptionally well-positioned to win future grants from the National Institutes of Health and other federal research funders, leading to dramatic innovations in the field. Congratulations to the 2023 first-year grantees. For a full list of all 15 recipients, including those who earned second-year funding, see hhf.org/erg.

Francisco BarrosBecker, Ph.D.

University of Washington

Project: Aminoglycoside compartmentalization and its role in hair cell death

Description: Hair cells, located in the inner ear, are highly specialized cells that have a central role in hearing and balance. We observed that hair cells, when exposed to different aminoglycoside antibiotics, could die rapidly or in a delayed manner. Microscopy imaging of this process showed that aminoglycosides leading to a delayed death tend to localize inside membranous structures called vesicles, inside hair cells. We hypothesize that the capture and delivery of aminoglycosides into vesicles is protecting the hair cell and delaying the toxic effects of these drugs.

Using the genetic and optical advantages of the zebrafish, coupled with super-resolution microscopy and automated image analysis, we aim to understand how vesicles collect and contain aminoglycosides within them. Each individual vesicle is part of a much larger and intricate vesicular network, and the activity of this network is essential for normal cell function. Unfortunately, how the vesicular network works in hair cells is not well understood. With this grant we aim to describe key steps during the process of aminoglycoside uptake and delivery into vesicles. In addition, tracing the maturation of vesicles containing aminoglycosides will help us better understand where toxicity, and therefore cell death, is triggered.

Long-term goal: 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 the 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 us 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.

Since the start of his scientific studies in Santiago, Chile, Barros-Becker has always been interested in understanding how cells and organisms can respond to their surroundings. Through his doctoral studies with Anna Huttenlocher, M.D., Ph.D., at the University of Wisconsin–Madison, he was able to study how immune cells migrate through complex environments and how they interact among them when actively responding to a wound. Currently he is a postdoctoral fellow in the lab of David Raible, Ph.D., at the University of Washington.

George Burwood, Ph.D.

Oregon Health & Science University

Project: Apical cochlear mechanics after cochlear implantation

Description: Cochlear implants are electrical devices that stimulate the inner ear to help restore hearing. Some implant patients are also fitted with a hearing aid that amplifies sound at the low frequencies. This hybrid implant approach maximizes the sound quality for these individuals who still have low frequency hearing. Unfortunately, some of these patients lose low frequency hearing following receipt of the cochlear implant, and the mechanisms are unknown.

One theory states that scarring caused by the presence of the cochlear implant disrupts the normal movement of sound waves through the inner ear. Using advanced imaging techniques that simultaneously measure nanometer scale vibrations, this project aims to reproduce cochlear implant-induced hearing loss in a rodent model and measure exactly how implantation and scarring influences the function of the inner ear at low frequencies. We will use the images we collect to build a 3D map of the scarring inside each cochlea and compare this data to the mechanical performance of the cochlea and hearing thresholds. If we can establish a cause for this hearing loss we can take steps to prevent it, leading to much improved quality of life for recipients of hybrid cochlear implants and possibly expand eligibility criteria for implantation.

Long-term goal: To establish, treat, and prevent implant-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 suppress scarring, and testing different electrode designs. Refining use of optical coherence tomography will also benefit research on other diseases of the inner ear, such as Ménière’s disease. Optical coherence tomography has the potential to play a big role in the future of both basic hearing science and hearing restoration.

Burwood completed his doctorate in auditory physiology with Ian Russell, Ph.D., and Andrei Lukashkin, Ph.D., at the University of Brighton, U.K., and is currently a postdoctoral researcher in the lab of Alfred Nuttall, Ph.D. (a 1989–1990 ERG scientist), at Oregon Health & Science University. Both roles focused on cochlear mechanics, and the latter introduced him to the power and versatility of optical coherence tomography.

Thank You to Our Grants Reviewers

As always, HHF extends its profound thanks to our peer reviewers, a revolving group of research scientists and clinicians who donate their time and expertise to provide comprehensive review of each and every ERG proposal HHF receives. Without these reviewers’ dedication to advancing hearing and balance science, supporting newer investigators’ careers, and sustaining HHF’s mission, HHF could not direct our donors’ support to the innovative and promising research HHF has had the privilege of funding since 1958. Support our research: hhf.org/donate.

Carolyn McClaskey, Ph.D.

Medical University of South Carolina

Project: Age and hearing loss effects on subcortical envelope encoding

Description: As we get older, it often becomes difficult to understand speech in noisy environments such as a crowded restaurant. Changes in auditory temporal processing are known to partly underlie these communication difficulties. Such altered temporal processing, including distorted neural encoding of sound envelopes, may arise from age- and hearing loss-related changes to subcortical auditory structures. This project uses a combination of behavioral, electrophysiological, and neuroimaging measures to assess how the auditory midbrain changes with age and age-related hearing loss and how this affects envelope encoding and speech-in-noise recognition. Long-term goal: To better understand how age and age-related hearing loss alter the neural signaling of the auditory system (specifically the auditory midbrain) and negatively impact speech communication, so that we can work toward developing effective clinical interventions and improving communication for older adults and adults with age-related hearing loss.

McClaskey earned her doctorate in psychology and cognitive science at the University of California, Irvine, and completed her postdoctoral studies in auditory neuroscience in the Hearing Research Program at the Medical University of South Carolina. She is now a research assistant professor in the department of otolaryngology at the Medical University of South Carolina. Her 2023 Emerging Research Grant is generously funded by Royal Arch Research Assistance.

Sharlen Moore, Ph.D.

Johns Hopkins University

Project: Modulation of neuro-glial cortical networks during tinnitus

Description: Tinnitus can be conceived as a disorder in which auditory and non-auditory brain areas are dysregulated and hyperexcitable, leading to the constant perception of a sound not externally generated. Neuromodulatory areas that send widespread signals across the brain have the potential to be responsible for this dysregulation as a change in gain or sensitivity.

Targets of these neuromodulatory areas can be either neurons or glial cells. Glial cells make up approximately half of the cells in our brain. They do not communicate through electric signals but do receive similar inputs as neurons do, and they also have the potential to modulate neuronal gain. This research will allow us to better understand the contribution of glial cells receiving inputs from longrange neuromodulatory centers to an overall hyperexcitability phenotype in auditory regions that gives rise to the perception of tinnitus. Long-term goal: To understand the complexity and temporal sequencing of tinnitus effectors with an integrative perspective, and to consider the interplay of diverse cell types that may lead to tinnitus, in order to provide an updated interpretation of this disorder; and to use glial cells as a key therapeutic target to treat tinnitus.

Moore received her doctorate in neuroscience from the Max Planck Institute of Experimental Medicine in Germany, with Livia de Hoz, Ph.D., and Klaus-Armin Nave, Ph.D., studying the role of myelin in mice auditory processing. She then returned to her native Mexico for postdoctoral studies at the Institute of Cellular Physiology, the National Autonomous University of Mexico, with Francisco Fernández de Miguel, Ph.D. She studied extrasynaptic serotonin release in the leech and participated in a project to understand how sounds modified the perception of visual art. She is now in the lab of Kishore Kuchibhotla, Ph.D., at Johns Hopkins University to study neuromodulatory circuits that influence learning and to understand the role of astrocytes in context-dependent high-order functions. Her 2023 Emerging Research Grant is generously funded by the Les Paul Foundation.

The ERG program is a competitive process that awards grants to only the most promising investigators. Recipients are exceptionally well-positioned to win future grants from the National Institutes of Health and other federal research funders, leading to dramatic innovations in the field. In fact, ERG alumni have gone on to be awarded an average $47 for every dollar of investment through ERG (2002–present).

Melissa Polonenko, Ph.D.

University of Minnesota–Twin Cities

Project: Identifying hearing loss through neural responses to engaging stories

Description: Spoken language acquisition in children with hearing loss relies on early identification of hearing loss followed by timely fitting of hearing devices to ensure they receive an adequate representation of the speech that they need to hear. Yet current tests for young children rely on non-speech stimuli, which are processed differently by hearing aids and do not fully capture the complexity of speech.

This project will develop a new and efficient test—called multiband peaky speech—that uses engaging narrated stories and records responses from the surface of the head (via EEG, or electroencephalography) to identify frequencyspecific hearing loss. Computer modeling and EEG experiments in adults will determine the best combination of parameters and stories to speed up the testing for use in children, and evaluate the test’s ability to identify hearing loss.

This work lays the necessary groundwork for extending this method to children and paves the way for clinics to use this test as a hearing screener for young children—and ultimately our ability to provide timely, enhanced information to support spoken language development. Long-term goal: To develop an engaging, objective clinical test that uses stories to identify hearing loss in young children and evaluate changes to their responses to the same speech through hearing aids. This goal addresses two important needs identified by the U.S. Early Hearing Detection and Intervention program and will positively impact the developmental trajectory of thousands of children who need monitoring of their hearing status and evaluation of outcomes with their hearing devices.

Polonenko received her doctorate in neurophysiology with the Institute of Medical Science at the University of Toronto. An audiologist and neuroscientist who trained in Canada, she completed postdoctoral studies in neuroscience and biomedical engineering at the University of Rochester Medical Center and is now an assistant professor in the speechlanguage-hearing sciences department at the University of Minnesota. Her 2023 Emerging Research Grant is generously funded by Royal Arch Research Assistance.

Support our research: hhf.org/donate.