MEET THE 2013 EMERGING RESEARCH GRANTEES
For the 2013 Emerging Research Grant cycle, Hearing Health Foundation supported research in the following areas:
For the 2013 Emerging Research Grant cycle, Hearing Health Foundation supported research in the following areas:
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.
Scott Cronin, M.D. is a resident in the Department of Otolaryngology at the University of Michigan. Cronin completed his undergraduate and medical school training at The Ohio State University. Cronin plans to pursue a career in Otology/Neurotology while continuing investigations of drug related hearing loss as a clinician-scientist.
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.
Brian Earl, Ph.D., CCCA, FAAA is an Assistant Professor in the Department of Communication Sciences & Disorders at the University of Cincinnati. Earl completed his Ph.D. training and postdoctoral work in audiology at the University of Kansas Medical Center. Prior to his doctoral training, Earl also completed clinical training in audiology at the University of Arizona and worked as a clinical audiologist at the University of Texas Medical Branch.
University of Wisconsin, Madison
Exploiting the “better ear” in bilateral cochlear implants for improved speech understanding in noisy situations
A recent study investigating selective attention abilities in cochlear implant users may point to a novel new method for improving the understanding of speech in a noisy environment. In that study, cochlear implant users showed significant improvement in speech understanding when instructed to attend to a target talker in one ear and ignore an interfering talker in the other. For some, there was a “better ear” for listening which yielded an even greater improvement. The aim of this work is to evaluate the feasibility of a novel strategy that takes advantage of these observations. A “better ear” strategy is proposed that combines (1) attending to a target talker in the “better ear” with (2) processing that separates the target talker’s speech from a noisy background, and delivers the target talker to the “better ear” and the remaining sound scene to the other ear. We believe this “better ear” strategy will be a significant step towards closing the gap in speech understanding performance between bilateral cochlear implant users and normal hearing listeners, and has the potential to provide significant improvements in speech understanding in noisy situations for patients with bilateral hearing aids, bimodal aids and other types of hearing impairments. Notably, this work is particularly important and relevant for children fitted with cochlear implants since they need to contend with noisy environments, such as classrooms, every day. The ability to hear better in these environments will lead to improved long-term social and educational development for these children.
Research area: Cochlear Implants; Central Auditory Processing Disorder
Long term goal of research: To close the gap in speech understanding performance between cochlear implant users and normal hearing listeners. The primary outcome of this study will help determine whether the “better ear” strategy will provide a significant benefit for cochlear implant users, and whether this strategy for listening is desirable. Positive results will provide an impetus for the development of new engineering solutions surrounding the implementation of this “better ear” strategy. In addition, our proposed experimental paradigm offers a unique opportunity to study auditory attention mechanisms used in understanding speech in noisy environments. This will help further develop our understanding of the human auditory system so that we can bridge the gap in hearing-in-noise performance between hearing impaired and normal hearing listeners.
Alan Kan, Ph.D. is currently a Research Associate in the Binaural Hearing & Speech Lab at the University of Wisconsin, Madison. Kan received both his Ph.D. and Bachelors in engineering from the University of Sydney, Australia, and has previously worked as a Consultant and Technical Projects Manager for Personal Audio and VAST Audio, respectively.
Dr. Kan is a Royal Arch Masons award recipient. The Royal Arch Masons support Emerging Research Grants in the area of Central Auditory Processing Disorder (CAPD).
Rochester General Hospital Research Institute
Differential Virulence gene expression of S. pneumoniae and Haemophilus influenzae in children with Acute Otitis Media & modulation of innate immune responses
Middle ear infections are the most common infectious disease among children leading to the use of antibiotics. Middle ear infections are typically followed by 4-12 weeks of middle ear effusion during which time children have diminished hearing leading to temporary delayed speech and language development. In developing countries, permanent hearing loss is not uncommon. Non-typeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae (Spn) are the two main bacteria that cause middle ear infections and are the target for new vaccine development. In the funded research, expression of various vaccine candidate proteins of NTHi and Spn in the nose (where middle ear infections start) and in the middle ear (where infections cause hearing loss) will be compared. Gene expression of the studied NTHi and Spn vaccine targets might be modulated by innate immunity of the host during disease progression and this too will be studied.
Research area: Middle Ear
Long term goal of research: To develop a vaccine to prevent middle ear infections, thereby reducing hearing loss from this common childhood infection. Towards this goal here we will evaluate several vaccine candidates of the most common causes of middle ear infections to determine whether immunity induced by vaccination will be effective to rid the child of the bacteria when they reside in the nose and/or when they gain entry to the middle ear. We will also study how the gene expression of the studied vaccine targets might be influenced by the child’s immunity system.
Ravinder Kaur, Ph.D. is a Research Scientist at the Rochester General Hospital Research Institute. Kaur’s research focuses on the pathogenesis of middle ear infections and immune response of children to those infections with a goal of facilitating a vaccine to prevent hearing loss.
Dr. Kaur is also the recipient of the George A. Gates Research Award, presented annually in perpetuity to an outstanding Emerging Research Awardee.
University of Washington
Relating behavior to brain in an audio-visual scene
Every day, listeners are presented with a barrage of sensory information in multiple sensory modalities. This can be overwhelming, but it also can allow for redundant information to be combined across the senses. This binding is well documented, but not well understood. Behavioral tests and brain imaging (magneto- and electroencephalography) will be used to study the brain activity associated with combing visual and auditory information. Particular interests include how congruent timing in auditory and visual stimuli allows them to be combined into a single sensory object, and what benefits this has for the listener. Using magneto- and electroencephalography will allow us to examine the brain’s response to our stimuli at a fine time-scale to determine what parts of the brain are involved in binding auditory and visual stimuli together. Listening to speech in noisy conditions can be difficult for normal-hearing listeners, but it is even harder for impaired listeners, such as hearing aid users, cochlear implant users, and those with central auditory processing disorders (CAPD). In this first phase, we will work with normal hearing listeners, to establish a baseline and understand how an individual's brain activity is related to their perception.
Research area: Central Auditory Processing Disorder; Fundamental auditory research,
Long term goal of research: This proposal is the beginning of a line of research investigating the specific behavioral effects of audio-visual binding and its processing in the brain. Behavioral tests with brain imaging will be used to investigate the importance of combining information across the visual and auditory senses, and establish relationships in brain activity and behavior, an effort that could inspire new audio-logical therapies.
Ross Maddox, Ph.D. is a postdoctoral researcher at the University of Washington. Maddox received his Ph.D. and M.S. in Biomedical Engineering from Boston University, and his B.S. from the University of Michigan.
Dr. Maddox is a Royal Arch Masons award recipient. The Royal Arch Masons support Emerging Research Grants in the area of Central Auditory Processing Disorder (CAPD).
University of Pittsburgh
The Influence of Dynamic Limb Movement on Activity within the Vestibular Nuclei: the Role of the Cerebellum
Balance is inherently a multi-modal sense. To maintain balance in upright stance or during walking, input from several modalities – namely the vestibular system (from the inner ear), proprioceptive system (from muscles and joints), and visual system – must be interpreted by the central nervous system and synthesized to understand body position in space relative to gravity. Our goal is to investigate how vestibular and limb proprioceptive inputs interact in the central nervous system, with a particular focus on the brainstem and cerebellum as these are key sites of multisensory processing of balance input. We anticipate that the results of these studies will have important implications for the understanding of multi-sensory processing within central vestibular pathways and for the clinical treatment of humans with vestibular disorders.
Research area: Vestibular and Balance Disorders; Vestibular Physiology
Long term goal of research: To elucidate the physiologic pathways responsible for integrating vestibular and proprioceptive information and to ultimately develop clinical strategies based upon these physiologic underpinnings to improve the health of humans with vestibular disorders.
Andrew McCall, M.D. received his M.D. from the University of California, Los Angeles where he went on to complete residency training in Otolaryngology. McCall’s sub-specialty training in Neurotology was completed at the Massachusetts Eye and Ear Infirmary, Harvard Medical School. McCall is an Assistant Professor in the Department of Otolaryngology at the University of Pittsburgh Medical Center where he provides clinical care for patients with otologic and neurotologic conditions, performs vestibular physiology research, and teaches.
Cincinnati Children’s Hospital Medical Center
Signaling defects due to Tricellulin deficiency
Mutations in a protein called Tricellulin lead to hereditary hearing loss in humans and degeneration of cochlear sensory cells and deafness in mice. In the inner ear, Tricellulin is found in the sensory epithelia at sites where three epithelial cells meet. The localization of Tricellulin at the junction between cells gives it the potential to respond to external cues and transmit the signals to the cell interior. The current project aims at uncovering the potential cellular signaling roles of Tricellulin by determining the gene expression changes in the inner ear of Tricellulin mutant mice compared to wild-type mice. The results of this study will not only add to the existing knowledge of the inner ear development and maintenance but also will examine the direct effects of losing a protein that helps preserve our hearing.
Research area: Fundamental Auditory Research
Long term goal of research: To determine the role of cell junction proteins in the inner ear function and elucidate the biological processes that are affected by genetic mutations in these proteins. As tight junctions are also the focus of drug delivery studies, it is valuable to realize the cellular functions of the associated proteins so that they can be manipulated for therapeutic purposes.
Gowri Nayak, Ph.D. completed her B.Sc. and M.Sc. degrees in India and received her Ph.D. degree in hearing research from the University of Sussex, England. Nayak is currently a research fellow at Cincinnati Children’s Hospital Medical Center, Cincinnati.
University of California, Los Angeles
Cellular modifications of the vestibular labyrinth: Intrinsic mechanisms following unilateral aminoglycoside treatment for Meniere’s disease
Intra-tympanic gentamicin is a widely used treatment for unilateral Meniere’s disease, primarily to reduce the activity in the affected ear and thereby reduce the frequency and severity of vertigo attacks. Though the treatments are applied to only one ear, the adaptive effects in the untreated ear have not been widely studied. At the same time, there is evidence indicating that the vestibular receptors exhibit intrinsic capabilities for modification or adaptation to alterations from the normal operating conditions. For example, the inner ear vestibular receptors may undergo a form of “sensory learning” when exposed to changes in the ambient operating conditions associated with spaceflight. An investigation of the contralateral labyrinth following treatments comparable to that associated with intra-tympanic gentamicin may provide clues as to alterations in the conserved ear. These capabilities may be recruited through rehabilitative measures (pharmacologic, physical therapy) to accelerate recovery to normal vestibular function. We propose to study the activity of individual neurons projecting to the conserved vestibular receptors, thereby providing a direct measure of the output of these neurons and by comparisons to our large database of untreated specimens, as well as to determine whether alterations in this activity ensues following adaptation to administration of gentamicin to the contralateral ear.
Research area: Meniere's disease; Ototoxicity
Long term goal of research: The proposed work is based on the intra-tympanic gentamicin treatment currently used for Ménière’s disease, but the implications of this study could have an even greater impact. Better understanding of the vestibular system’s ability to respond to damage reveals the possibility of retraining the non-lesioned ear, akin to physical therapy. Though most animal studies use unilateral labyrinthectomy as their disease model, such complete loss is rare in the clinical setting. The intra-tympanic gentamicin treatment for Ménière’s disease is not the same as a labyrinthectomy, as the lesions are likely to be partial. Thus, the experiment described here, a direct test of whether peripheral plasticity ensues following partial lesions, is more translationally realistic compared to the labyrinthectomy. Therefore, an investigation into the effects of a less severe lesion, such as the gentamicin regimen proposed here which preserves spontaneous neuronal activity, would be of significant translational value.
Peihan Orestes, Ph.D. did graduate work at the University of Virginia focused on using various electrophysiological and imaging techniques to study the role of low-voltage activated calcium channels in neuropathic pain and analgesia. Orestes continued her to work in sensory neuroscience at the National Institute of Dental and Craniofacial Research. Orestes is currently at the University of California Los Angeles, investigating the modifications of vestibular afferents after gentamycin treatment.
University of Massachusetts, Amherst
The Impact of Total Communication on the Auditory Perception of Speech
For decades, most children with severe-to-profound hearing loss were educated in special schools for the deaf. In more recent years, increasing numbers of these children have been partially or fully main-streamed and educated along-side their peers with normal hearing. Much debate has ensued regarding the best language of instruction (sign-only, sign+speech, speech only) for them. It is generally thought that a symbolic, gesture-based language system, such as manually-coded English used as part of simultaneous communication methods, provides a facilitative benefit. However, there is not enough information about how children combine manual and spoken cues in this type of communication system to draw firm conclusions about optimal approaches to classroom teaching that best support aural reception of spoken language. We plan to ask and answer a very specific question: What is the direct effect of simultaneously delivered sign language on the perception of speech for children with hearing loss developing spoken language? The research approach builds from the observation that perception of speech that has been artificially degraded (e.g., to mimic a hearing loss) is strikingly improved when listeners have knowledge of the content of the message. The proposed study applies this hypothesis to children with hearing loss to determine whether signs serve in part as a prime to improve auditory perception of speech.
Research area: Auditory Development; Congenital Hearing Loss; Fundamental Auditory Research
Long term goal of research: To assess how total communication – the combined use of manual signs, speech, and speech-reading – can most effectively be employed as a habilitation strategy to improve auditory perceptual abilities.
Sarah F. Poissant, Ph.D. is an Associate Professor in the Communication Disorders Department at the University of Massachusetts Amherst. Poissant’s research program focuses on maximizing auditory speech perception in listeners with hearing loss and understanding how the characteristics of real-world listening environments negatively impact speech understanding in cochlear implant users.
Dr. Poissant's project is partially funded by the HHF Centurions.
Northeast Ohio Medical University
Effects of developmental conductive hearing loss on communication processing: perceptual deficits and neural correlates in an animal model
Conductive hearing loss (CHL), which reduces the sound conducted to the inner ear, is often associated with chronic ear infections (otitis media). There is growing awareness that CHL in children is a risk factor for speech and language deficits. However, children often have intermittent bouts of hearing loss and receive varying treatments. My research uses an animal model in which the duration and extent of CHL can be effectively controlled. This research will identify parameters of natural vocalizations (such as slow or fast changes in pitch or loudness) that are poorly detected after early CHL. Neural responses from the auditory cortex will be recorded while animals behaviorally distinguish vocalizations that vary in specific ways. This will reveal the specific vocalization components that are perceptually impaired by developmental hearing loss. These components should be used as targets for intervention and remediation. Creating training paradigms for children that target these parameters should improve speech perception and comprehension.
Research area: Hearing Loss; Auditory Development; Auditory Physiology; Fundamental Auditory Research
Long term goal of research: To identify neural mechanisms that impairs auditory perception of natural sounds as a result of hearing loss. This will show how the brain distinguishes sounds from different sources in complex environments. Neurophysiological, perceptual, and computational techniques to study animal models of hearing loss were applied. This multifaceted approach allowed the identification of neural impairments in more detail than if it was obtained when studying humans, yet is directly applicable to clarify human hearing problems and establish effective treatments.
Merri Rosen, Ph.D. received a B.A. in Psychology and Music from Wesleyan University, an M.S. in Neurobiology from Brandeis University, and a Ph.D. in Neurobiology from Duke University. Rosen conducted postdoctoral research at Cornell University and New York University, and is now an Assistant Professor at Northeast Ohio Medical University.
Dr. Rosen is a Royal Arch Masons award recipient. The Royal Arch Masons support Emerging Research Grants in the area of Central Auditory Processing Disorder (CAPD).
Brigham and Women’s Hospital; Harvard Medical School
An integrated paradigm for efficient hearing loss gene discovery
Knowing the genetic cause of hearing loss allows early diagnosis before the onset of noticeable symptoms. It also informs the choice of optimal management plans, and predicts risks for relatives including future babies. We aim to identify novel hearing loss genes by studying three large families with hereditary hearing loss from an isolated population. We will integrate new High- Throughput (HTP) sequencing technology with family-based analyses and prior research findings concerning hearing into the Shared Harvard Inner Ear Laboratory Database (SHIELD). This integrated approach will enable efficient identification of one or more hearing loss genes in these families. The discovery of novel genes will increase our knowledge, enable early diagnosis, and ultimately lead to improved patient care.
Research area: Fundamental auditory research
Long term goal of research: To translate genetic research findings into accurate and sensitive clinical molecular diagnostic tests to improve care for patients.
Jun Shen, Ph.D. is an Assistant Director of the Laboratory for Molecular Medicine at the Partners Healthcare Center for Personalized Genetic Medicine and Instructor in Pathology at Harvard Medical School and Brigham and Women’s Hospital. Shen received her Ph.D. at Harvard University and her research focuses on genetic testing and gene discovery for hearing loss.
Harvard Medical School
Development and Physiology of the Endolymphatic Duct and Sac in Zebrafish
Abnormalities in our sense of hearing and balance are incapacitating in the extreme, and, when subtle, cause psychological distress. Meniere’s disease is an inner ear disease with unclear causes that is inferred from episodes of vertigo, hearing loss, tinnitus, and the sensation of fullness in the ear that can last two to four hours. An unstable inner ear environment is believed to underlie Meniere’s disease. Recently, Swinburne has developed methods to image the live development and physiology of the portion of the Zebrafish ear conserved in humans and believed to be dysfunctional in Meniere’s disease: the endolymphatic duct and sac. With these methods, Ian hopes to gain basic understanding of how the inner ear’s environment is normally maintained and how a defect can lead to a disease.
Research area: Meniere’s disease
Long term goal of research: To understand how the endolymphatic duct and sac stabilize the inner ear’s environment and to identify ways to restore or elevate this function to mitigate or cure Meniere’s disease.
Ian Swinburne, Ph.D. received a B.S. in Cell and Molecular Biology from Cornell University in 2001 and a Ph.D. in Cell Biology from Harvard Medical School with Pamela Silver. Swinburne conducted Post- Doctoral research at New York University in Developmental Genetics with Debbie Yelon and currently conducts research at Harvard Medical School on Systems Biology of the inner ear with Sean Megason.
Oregon Health & Science University
Hyperexcitability dependent on Neuromodulatory state in the cochlear nucleus
Tinnitus affects approximately 50 million people in the USA, and millions more worldwide. However, the mechanisms underlying tinnitus are poorly understood. The dorsal cochlear nucleus (DCN), one of the first stations of the ascending auditory pathway, receives dense serotonergic input. Recent evidence indicates that the DCN may be a site of central tinnitus, and it is possible that serotonin might play a role in the generation or modulation of central tinnitus. Moreover, serotonin reuptake inhibitors (SSRIs) typically used as antidepressants in the treatment of depression and anxiety disorders, have been explored as a treatment for tinnitus. The goal of this research is to identify the cellular targets of serotonin and SSRIs in the DCN and understand their functional roles. The ultimate goals of this research are to understand how serotonin influences the output of the DCN, and whether serotonin may have a role in tinnitus.
Research area: Tinnitus
Long term goal of research: To understand how different neuromodulators control the neural activity in the central auditory system and their role in pathological auditory processing.
Zhengquan Tang, Ph.D. received his Ph.D. in neuroscience from the University of Science and Technology of China in 2007. Tang began a postdoctoral position in the laboratory of Dr. Yong Lu at Northeast Ohio Medical University, OH. Tang began a second postdoctoral position in the laboratory of Dr. Laurence Trussell at Oregon Health & Science University.
St. Jude Children's Research Hospital
Conditional Reprogramming of Otic Stem Cells: Development of a Novel In-Vitro Hair Cell Line
One of the major limitations in studies of hearing loss is the inability to study the phenomenon of hearing in a petri dish (in-vitro), thereby limiting the use of tools that are essential for understanding the causes of, and treatments for, hearing loss. In addition to this obvious limitation, the use of in-vitro studies is hindered primarily by technical limitations related to the low abundance of hair cells that are responsible for our sense of hearing. Researchers have attempted to overcome the issue of insufficient cell numbers by creating cell lines that mimic the properties of human hair cells, but success of these approaches have been limited. The goal of the proposed experiments is to utilize approaches from other fields to create a cell line that will allow for infinite proliferation of low abundance cells that can be turned into hair cells when needed, thus providing a limitless supply of hair cells for the study of hearing loss.
Research area: Hair Cells; Hearing Loss
Long term goal of research: To identify drugs that can modulate the differentiation of hair cells, focusing primarily on compounds that promote hair cell formation, which we believe, will be of therapeutic benefit to people with hearing loss. To this end, we plan to utilize high throughput screening to test hundreds of thousands of compounds for potential effects on hair cell formation. We plan to combine the hair cell line that we create with various tools for tracking the developmental state of the cell to aid our evaluation of drugs that increase the number of all viable hair cells and to potentially extend our investigation to specific subtypes of hair cells that play distinct roles in hearing loss.
Brandon Walters, Ph.D. received his Ph.D. and M.S. degrees at the University of Alabama, Birmingham. Currently, Walters is a Post-Doctoral Research Fellow at St. Jude Children’s Research Hospital. Walters has been actively investigating molecular mechanisms of diverse biological processes since the start of his graduate education.
Children’s Hospital Boston and Harvard Medical School
Functions of supporting cell-derived neurotrophin-3 in noise-induced hearing loss
Emerging evidence shows that “benign” noise levels, initially thought to only result in temporary hearing impairment, can cause irreversible damage to the connections between hair cells the auditory neurons, and the synapses, which can lead to a permanent hearing decrease later in life. Currently, we have a limited understanding of how these synapses are maintained in the healthy cochlea and how they can be regenerated after noise overexposure. The overall goal of this study is to examine the potential of the neurotrophic factor, neurotrophin-3 (NT-3), to assist in preserving or regenerating these synaptic connections in cochlea after noise overexposure. We have generated genetic mouse models that allow us to remove or overproduce NT-3 from the supporting cells, which are the cells surrounding the sensory hair cells. We have found that NT-3 produced from the supporting cells is critical for regulation of hearing sensitivity and synaptic density in the cochlea. Based on this finding, we propose that NT-3 may present a novel therapeutic agent for NIHL. In this proposal, we will use these mouse models to address the following questions: does removing NT-3 exacerbate the damage to the loss of synapses and hearing sensitivity after noise overexposure? Does overproducing NT-3 prevent or promote recovery from noise-induced loss of synapses and hearing? These experiments will provide us with a better understanding of the pathophysiology of NIHL and the potential of neurotrophin-based therapeutics for treating hearing loss.
Research area: Fundamental Auditory Research; Noise-Induced Hearing Loss
Long term goal of research: To assess the efficacy of NT-3 and possibly its agonists/modulators as therapeutics for sensorineural hearing loss.
*Guoqiang Wan, Ph.D. received his B.Sc in biochemistry in 2004 and Ph.D in neuroscience in 2011, from National University of Singapore. Wan is now a postdoctoral research fellow in F.M. Kirby Neurobiology Center at Children’s Hospital Boston and Harvard Medical School.
University of Utah
Understanding the function of PDZD7 in hair cells
Usher syndrome is a devastating genetic disease affecting both hearing and vision. It is the leading genetic cause of combined deafness and blindness in the world. Usher syndrome is clinically and genetically heterozygous. It is classified into three clinical types according to the severity of hearing and vestibular symptoms. Zou's studies focus on type 2, which is the dominant form of Usher syndrome and characterized by congenital moderate degree of hearing loss, normal vestibular function, and retinitis pigmentosa. PDZD7 was recently reported to exacerbate the symptoms and contribute the digenic form of Usher syndrome type 2 when patients carry heterozygous PDZD7 mutations. Zou has successfully generated a Pdzd7 knockout mouse. Using this animal model, Zou plans to investigate the function of PDZD7 during hair bundle development in the cochlea. This study will be significant for the future diagnosis and treatments for Usher syndrome type 2.
Research area: Usher Syndrome
Long term goal of research: To develop mechanism-based treatments for Usher syndrome by understanding the formation of USH protein interactomes and their functions in the development and maintenance of hair bundles in hair cells.
Junhuang Zou, Ph.D. received his Ph.D. in Genetics at the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences. Zou is now a postdoctoral research associate in the John A. Moran Eye Center, University of Utah.
East Carolina University
Place specificity of electrical stimulation with a cochlear implant and its relationship to neural survival and speech recognition
Modern cochlear implants code a speech signal by dividing it into spectral channels and modulating trains of biphasic electrical pulses with the low-frequency temporal envelope from each channel. Perception with a cochlear implant therefore is dependent on two factors: the acuity of processing the low frequency amplitude modulations and the place specificity of excitation. Cochlear implant users have demonstrated amplitude modulation detection similar to that found in normal hearing ears with larger individual variability, nonetheless the challenge of the prosthesis lies with the poor place specificity. Ideally, the output of an electrode should target a specific population of nerve fibers. However spread of excitation is often large, leading to neural interactions between channels. The first aim of the research is to investigate whether the underlying cause of channel interaction is the status of neural survival near the stimulation sites. The hypothesis is that excitation is more likely to spread further from a stimulation site in the cochlea when the density of surviving spiral ganglion cells is sparse. Neural status of a stimulation site will be estimated using a non-invasive psychophysical measure that correlates with the count of spiral ganglion cells in implanted animals. Place specificity of excitation will be measured by a psychophysical forward-masking procedure that is widely used to assess spatial tuning in electrical hearing. The second aim of the research is to examine the effects of place specificity on speech perception that requires mainly the spectral cues. The rationale is that poor place specificity would cause a reduction in spectral resolution or smearing of spectral speech cues. Proposed speech recognition tasks that demand good spatial tuning are perception of sine-wave speech, also known as the spectral skeleton of speech, and perception of speech presented in background noises.
Research area: Cochlear Implants
Long term goal of research: If the proposed hypothesis is correct, that is, poor neural survival predicts poor spatial tuning, we will seek to ask the question whether the temporal processing acuity of the activated neurons at the site with low cell density would also be compromised. Once the relationship between temporal and spatial acuity is determined, we will examine the relative importance of the temporal and spatial acuity for speech recognition. The two acuities might not be equally important, or that they might be contributing to different aspects of speech recognition. With this information, the long term goal is to optimize implant user’s speech processing MAPs by strengthening the perception acuity that is the most important for speech recognition in the ear.
Ning Zhou, PhD, has recently joined the Department of Communication Sciences and Disorders at East Carolina University for a faculty position. Dr. Zhou received a master's degree in Linguistics and a Ph.D. degree in Hearing Sciences from Ohio University. She worked as a postdoc research fellow at the Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan from 2010 to 2013. Her research area is psychophysics and perception in humans with cochlear implants. Her recent research focuses on improving speech recognition in electrical hearing by customizing the speech processing strategies of the devices on an individual basis.
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.
Yoojin Chung, Ph.D. received a Ph.D. in biomedical engineering from Boston University in Massachusetts. Chung is a postdoctoral fellow at Massachusetts Eye and Ear Infirmary and Harvard Medical School.
Dr. Chung is a Royal Arch Masons award recipient. The Royal Arch Masons support Emerging Research Grants in the area of Central Auditory Processing Disorder (CAPD).
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.
Brenton Cooper, Ph.D. received his B.S. in psychology from the University of New Mexico in 1993. In 2003, he completed his Ph.D. in psychology at the University of Utah. Cooper then went on to a National Institutes of Health-funded postdoctoral position and a research faculty appointment in the biology department at the University of Utah. In 2007, Cooper joined the faculty at Texas Christian University as an assistant professor of psychology in the College of Science and Engineering.
Dr. Cooper is a Royal Arch Masons award recipient. The Royal Arch Masons support Emerging Research Grants in the area of Central Auditory Processing Disorder (CAPD).
University of Iowa
Misexpression of Neurog1 combined with delayed deletion of Atoh1 provides a novel model
Contemporary research is focusing on the regeneration of hair cells in hearing loss using Atoh1. Reconstitution of the organ of Corti requires proper organization of the two types of hair cells, inner and outer hair cells, as well as supporting cells. Recent data showed that level of Atoh1 determines the degree of survival of different types of hair cells. Jahan’s previous work demonstrated the survival of some organ of Corti-like cells without Atoh1 if replaced by a closely related transcription factor, Neurog1. It is now Jahan’s intent to investigate the effect of Atoh1 substitution with Neurog1 combined with a delayed loss of Atoh1 expression in viable animals. This combined mutant offers for the first time a critical test of presumed causalities of molecular mechanism that may regulate the patterning of the organ of Corti, including hair cell and supporting cell differentiation.
Research area: Hair Cell Regeneration
Long term goal of research: To define the correct dose and duration of Atoh1 expression for type-specific hair cell development which will provide novel insights into hair cell regeneration.
Israt Jahan M.B.B.S, Ph.D. received her Ph.D. in medical sciences from Gifu University in Japan. Jahan began postdoctoral training in inner ear neurosensory development at Creighton University in Nebraska before moving to the University of Iowa to continue her work.
Ascertaining the contribution of Piezo proteins to Mechano-transduction in Zebrafish hair cells
The proteins that mediate the transformation of mechanical forces into electrical signals within the sensory cells that convey the senses of hearing and balance have yet to be identified. This lack of knowledge has undoubtedly hindered the identification of therapeutic compounds capable of alleviating the complications that arise from disorders in hearing and balance, such as deafness and vertigo. Recently, a member of the novel piezo protein family has been shown to contribute to cutaneous mechano-sensation, raising the possibility that related family members may contribute to hearing and balance. Dr. Low will utilize the simple vertebrate commonly known as zebrafish, to address this possibility.
Research area: Fundamental Auditory Research
Long term goal of research: To identify therapeutic agents that can restore normal hearing and balance in individuals who have either lost these senses, or suffer from conditions caused by abnormal activity in the sensory cells that mediate them.
Sean Low Ph.D. received a B.S. in Cellular and Molecular Biology in 2001, and a Ph.D. in Neuroscience in 2008 from the University of Michigan. Desiring to focus on sensory transduction, Low sought out a postdoctoral position in the Saint-Amant lab at the University of Montréal from 2009 – 2011, where he examined the role of a Piezo protein in cutaneous mechano-transduction. These studies evolved into an interest in mechano-transduction processes in general, and a second postdoctoral position with Dr. Hudspeth at The Rockefeller University beginning in 2011.
Dr. Low is also The Todd M. Bader Research Grant of the Barbara Epstein Foundation, Inc., Recipient. This research award is funded in part by The Todd M. Bader Research Grant of The Barbara Epstein Foundation, Inc.
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 area: Otitis Media; Genetics
Long term goal of research: To improve the clinical prevention of chronic infections; therefore decreasing pediatric antibiotic use, surgery, and deafness.
Ani Manichaikul, Ph.D. is an assistant professor at the University of Virginia Department of Public Health Sciences and Center for Public Health Genomics. Manichaikul received her Ph.D. in biostatistics at the Johns Hopkins School of Public Health. Manichaikul’s research focuses on statistical genetics and genetic epidemiology in human cohorts, as well as translational research bridging mouse and human genetic studies.
University of Florida College of Medicine
Prevention of aminoglycoside-induced hearing loss with the mitochondria-targeted antioxidant MitoQ
Aminoglycoside antibiotics, such as gentamicin, are commonly used to treat serious infections due to bacteria. However, these drugs can cause hearing loss. At present, there is no solution to prevent hearing loss caused by aminoglycoside antibiotics. This research will determine if the antioxidant MitoQ will prevent hearing loss induced by aminoglycoside antibiotics.
Research area: Hearing loss, Ototoxicity
Long term goal of research: To develop and apply practicable intervention strategies to prevent hearing loss induced by drugs that are toxic to the inner ear.
Carolyn Ojano-Dirain, Ph.D. received a B.S. in animal nutrition from the University of the Philippines in Los Baños, Laguna, Philippines, in 1997. In 2002, Ojano-Dirain received a M.S. in poultry nutrition and in 2006, a Ph.D. in cell and molecular biology, both from the University of Arkansas. Ojano-Dirain’s postdoctoral training in mitochondrial metabolism and gene therapy was at the Department of Medicine at the University of Florida and she is currently a faculty member in the Department of Otolaryngology—Head and Neck Surgery at the University of Florida.
Oregon Health & Science University
Changes in Residual Hearing in a Hearing-impaired Guinea Pig Model of Hybrid Cochlear Implants (CIs)
The goal of the current study is to understand mechanisms of hearing loss with “hybrid” or “electro-acoustic” cochlear implants (CIs), a new type of CI designed to preserve low-frequency hearing and allow combined acoustic-electric stimulation in the same ear. Hybrid CI users perform significantly better than standard CI users on musical melody recognition, voice recognition, and speech recognition in the presence of background talkers. However, approximately 10% of hybrid CI patients lose all residual hearing, and another 20% lose 20-30 dB after implantation. We hypothesize that in addition to surgical trauma, electrical stimulation through the hybrid CIs also damages cochlear cells, leading to the residual hearing loss (HL). Aim 1 is to determine the contribution of electrical stimulation to the residual HL in hybrid CI guinea pigs with noise-induced steeply-sloping high frequency hearing loss (NIHFHL). Aim 2 is to examine the effect of electrical stimulation on the cochlear pathology. The findings will guide the development of strategies to prevent hearing loss with electrical stimulation, and allow extension of the hybrid concept to all cochlear implant recipients with usable residual hearing.
Research area: Cochlear implants
Long term goal of research: To improve residual hearing preservation with “hybrid” or “electro-acoustic” cochlear implants (CIs), a new type of CI designed to preserve low-frequency hearing and allow combined acoustic-electric stimulation in the same ear.
Lina Reiss Ph.D. has been an Assistant Professor in the Department of Otolaryngology-Head and Neck Surgery at Oregon Health and Science University (OHSU) since 2010. Previously, Reiss was a postdoctoral scholar at the University of Iowa where she conducted research in the Hybrid cochlear implant clinical trials. Reiss earned her doctorate in Biomedical Engineering from Johns Hopkins University in 2005.
Baylor College of Medicine
Development of Biomarkers to Study Strial Development and Degeneration
The stria vascularis is a specialized tissue in the inner ear, localized in the lateral wall of the cochlea. This tissue generates endolymph, a special fluid that is rich in potassium and provides the driving force for the function of the sensory cells in the ear. Strial defects are implicated in many human syndromes involving profound hearing loss and are one of the main causes of presbycusis (age related hearing loss). In spite of its importance for normal hearing, we know very little about the development of the stria vascularis. The goal of this project is to identify the genes that are responsible for strial development, and that present the potential to restore or regenerate damaged stria vascularis in cases of both congenital or age related hearing loss.
Research Area: Stria Vascularis Atrophy/Development
Long Term Goal: To understand how the development of the stria vascularis and apply this knowledge towards the regeneration and/or repair of damaged stria vascularis in cases of congential defects or age related hearing loss.
Martin Basch, Ph.D. received his Ph.D. in developmental biology at the California Institute of Technology. He worked as a postdoctoral fellow with Drs. Andrew Groves and Neil Segil at House Ear Institute. He is currently an Instructor in Dr. Andrew Groves’ lab at Baylor.