For the 2014 Emerging Research Grant cycle, Hearing Health Foundation supported research in the following areas:

 

+ Samira Anderson, Ph.D.

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University of Maryland
Neural adaptation in new hearing aid users

Hearing loss is among the top three chronic health conditions of senior citizens, affecting approximately 50% of the population > 65 years. Despite this high prevalence of hearing loss, only 20% of senior citizens with hearing loss use a hearing aid. Why do senior citizens reject hearing aids after trying them, despite available advances in hearing aid technology? One possibility is that current hearing aid fitting practices focus on providing adequate volume but do not take into account what happens to the amplified signal as it travels along the brain’s pathways. Aging and hearing loss can have a detrimental effect on the brain’s sound processing, and at this time, we don’t understand the impact of hearing aid use on sound processing. Furthermore, the brain’s responses to amplified sound may change over the course of time to the extent that hearing aid settings may need to be re-adjusted. This study compares brainstem and cortical-evoked electroencephalographic responses to speech with and without hearing aids in individuals who have never worn hearing aids, and then evaluates changes in the brain’s responses to amplified speech over the course of 6 months. This information should help hearing aid program designers and audiologists to optimize the hearing aid fitting.

Research Area: Auditory Physiology; Central Auditory Processing; Hearing Loss; Hearing Aids

Long term goal of research: The long-term goals of this project are to improve the hearing aid fitting process through assessment of the brain’s sound processing and to determine how this processing changes with hearing aid use over the course of six months. The use of brainstem and cortical-evoked electroencephalographic responses in the hearing aid fitting may help the clinician to understand why the hearing aid user is having difficulty understanding speech in certain difficult listening environments.

Samira Anderson, Ph.D. uses electrophysiology to assess how the brain processes speech signals. In particular, she is interested in the effects of aging and hearing loss on the brain’s speech processing. She uses her clinical experience as an audiologist to conduct translational work to address the speech understanding difficulties experienced by older adults, and to assess the impact of intervention (hearing aids, cochlear implants, and auditory training) on neural processing and speech understanding. Dr. Anderson is a General Grand Chapter Royal Arch Masons International award recipient. The Royal Arch Masons support Emerging Research Grants in the area of Central Auditory Processing Disorder (CAPD).

Dr. Anderson is a General Grand Chapter Royal Arch Masons International award recipient. The Royal Arch Masons support Emerging Research Grants in the area of Central Auditory Processing Disorder (CAPD).

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+ Cynthia Grimsley-Myers, Ph.D.

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Emory University
The essential role of URB, a novel secreted protein, in cochlear development and planar cell polarity signaling

Hearing depends on highly structured hair bundles in the cochlea properly oriented towards the lateral border of the cochlear duct. Abnormalities in this hair bundle structure or its orientation results in hearing loss, for example in the hereditary disorder Usher syndrome. However, the molecular mechanisms that build the polarized structure of individual hair cells remain poorly understood. Our research focuses on the role of a novel secreted protein, URB, in hair bundle morphogenesis and cochlear development. In particular, we are testing whether URB functions as part of a Planar Cell Polarity (PCP) signaling pathway, a highly conserved pathway of widespread biological interest. We are also investigating possible links between URB and the Usher syndrome network of proteins. We hope that defining these roles for URB in bundle morphogenesis will help in the design of rational therapies for the treatment of Usher syndrome and other forms of hereditary hearing loss in the future.

Research area: Auditory Development; Auditory Physiology; Fundamental Auditory Research; Usher Syndrome

Long-term goal of research: To understand the specific cellular and molecular functions of URB in hair bundle morphogenesis and planar cell polarity (PCP) signaling and how mutations in URB/PCP signaling contribute to hearing loss.

Cynthia Grimsley-Myers, Ph.D. received her Ph.D. in Pharmacology from the University of Virginia in 2005. She then conducted post-doctoral research in the laboratory of Dr. Xiaowei Lu at the University of Virginia where she studied signaling mechanisms underlying inner ear development and hair cell polarization. She is currently a research instructor at Emory University where she investigates cochlear development.

Dr. Grimsley-Myers is funded by HHF's New York Council.

+ Srikanta Mishra, Ph.D.

New Mexico State University
Medial Efferent Mechanisms in Auditory Processing Disorders

Many individuals experience listening difficulty in background noise despite clinically normal hearing and no obvious auditory pathology. This condition has often received a clinical label called auditory processing disorder (APD). However, the mechanisms and pathophysiology of APD are poorly understood. One mechanism thought to aid in listening-in-noise is the medial olivocochlear (MOC) inhibition— a part of the descending auditory system. The purpose of this translational project is to evaluate whether the functioning of the MOC system is altered in individuals with APD. The benefits of measuring MOC inhibition in individuals with APD are twofold: 1) it could be useful to better define APD and identify its potential mechanisms, and 2) it may elucidate the functional significance of MOC efferents in listening in complex environments. The potential role of the MOC system in APD pathophysiology, should it be confirmed, would be of significant clinical interest because current APD clinical test batteries lack mechanism-based physiologic tools.

Research Area: Auditory Development; Auditory Physiology; Central Auditory Processing Disorder

Long-term goal: The overall goal is to understand the role efferent mechanisms in auditory processing, learning and disability. The translational goal is to develop mechanism-based and physiological tests for assessing auditory processing.

Srikanta Mishra, Ph.D. earned his PhD from the University of Southampton, England and received postdoctoral training from the House Ear Institute, Los Angeles. He investigates the role of efferent mechanisms in hearing and auditory disorders in humans.

Dr. Mishra is a General Grand Chapter Royal Arch Masons International award recipient. The Royal Arch Masons support Emerging Research Grants in the area of Central Auditory Processing Disorder (CAPD).

Dr. Mishra is a General Grand Chapter Royal Arch Masons International award recipient. The Royal Arch Masons support Emerging Research Grants in the area of Central Auditory Processing Disorder (CAPD).

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+ Shikha Tarang, Ph.D.

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Creighton University
Transient and Regulated Dominant-Negative RB1 Inhibition to Regenerate Hair Cells

Our ability to hear and communicate depends primarily on the sensory hair cells (HCs) and their associated spiral ganglion neurons (SGNs). Unfortunately, mammalian HCs and SGNs are not naturally replaceable, and their loss results in neurosensory hearing loss and balance impairment. To this date, any attempts to regenerate lost sensory HCs have been challenged by the early embryonic lethality of complete knockout mice or massive cell death after conditional deletion of targeted genes. In this light, we sought to design a new system that combines the inducible nature of an antibiotic-controlled system with the lysosomal fusion protease pre-procathepsinB (CB) to generate an inducible, temporal, and reversibly conditional mouse model. To build upon our laboratory’s expertise, we applied this technology to generate a mouse model carrying a transgenic version of the of the retinoblastoma (Rb1) gene. The Rb1 gene is a key component of cell cycle regulation. In addition to its role in cell proliferation, Rb1 expression in the inner ear also affects differentiation and survival of HCs and their associated supporting cells (SCs). Rb1 deletion leads to the production of supernumerary HCs and SCs. However, just like a number of other genes considered potential candidates for HC regeneration, complete and permanent elimination of Rb1 results in massive apoptosis, and as such, should be avoided at all costs. This study will allow us to characterize this newly generated model of transient and reversible gene ablation and gather information supporting pre-clinical studies on HC regeneration.

Research Area - Hair Cell Regeneration; Hearing Loss; Noise-Induced Hearing Loss; Ototoxicity

Long term goal of the research – To develop therapeutic interventions to prevent hearing loss and restore lost hearing. To this date, no pharmaceutical drugs have been effective in restoring auditory function after HCs are lost. This fact fuels our continuous search for alternative strategies to prevent and treat hearing loss.

Shikha Tarang, Ph.D., received her graduate training in Immunology at the Banaras Hindu University, India. Currently, Dr. Tarang is a Postdoctoral Research Associate in the department of Oral Biology at the Creighton University School of Dentistry. Dr. Tarang’s research interests include hair cell regeneration and otoprotection.

Dr. Tarang is funded by the Hulme family.

+ Daniel Winkowski, PH.D.

University of Maryland
Noise trauma induced reorganization of the auditory cortex

Tinnitus (‘ringing in the ears’) is a debilitating condition that is experienced by millions of people worldwide. Tinnitus is frequently seen after noise trauma to the ear. One of the core hypotheses of the etiology of tinnitus is that the percept of ‘ringing in the ears’ is generated by changes in patterns of neural activity in brain circuits at many levels of the auditory pathway. One brain area thought to be at least partly responsible for the tinnitus percept is the primary auditory cortex (A1). However, the precise changes in neural activity within local neuron populations have not been investigated directly. The goal of the proposed project is to probe how noise trauma affects both large- and local-scale organization of A1 brain circuits with unprecedented spatial and cellular resolution in an animal model of tinnitus. Proposed experiments will use state-of-the-art optical imaging approaches to investigate how entire auditory cortical areas (large-scale) and auditory cortical microcircuits (local-scale) are disrupted by noise trauma. A multi-level understanding of circuit dynamics underlying tinnitus (from single neurons to complete representations) will enhance our understanding of precisely how cortical circuits remodel after noise trauma and, in turn, develop and identify strategies by which this debilitating condition can be repaired.

Research Area: Auditory Physiology, Fundamental Auditory Research, Noise-Induced Hearing Loss, Tinnitus

Long Term Research Goal: The long-term goal for the current project is to understand tinnitus at the level of neural circuits. Our approach offers a rather unique opportunity to sample activity within large-scale representations and local populations of neurons and, in turn, will reveal precisely how A1 micro-circuits are affected by traumatic insult to peripheral sensory organs. Thus, I intend on using this approach to build a more comprehensive understanding of how cortical micro-circuits change as a result of noise trauma. Such a level of understanding is essential to advance our efforts to reduce or even reverse the impact noise trauma has on its patients and our society.

Daniel Winkowski, Ph.D. earned a B.S. from Fordham University and a Ph.D. in Biology from Temple University. He conducted postdoctoral research at Stanford University and the University of Maryland and is now an Assistant Research Scientist in the Institute for Systems Research at the University of Maryland.

Dr. Winkowski is a General Grand Chapter Royal Arch Masons International award recipient. The Royal Arch Masons support Emerging Research Grants in the area of Central Auditory Processing Disorder (CAPD).

Dr. Winkowski is a General Grand Chapter Royal Arch Masons International award recipient. The Royal Arch Masons support Emerging Research Grants in the area of Central Auditory Processing Disorder (CAPD).

+ Alan Kan, Ph.D.

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 General Grand Chapter Royal Arch Masons International award recipient. The Royal Arch Masons support Emerging Research Grants in the area of Central Auditory Processing Disorder (CAPD).

+ Zhengquan Tang, Ph.D.

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Oregan 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.

Dr. Tang is the recipient of the George A. Gates Research Award, presented annually in perpetuity to an outstanding Emerging Research Awardee.

+ Guoqiang Wan, Ph.D.

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University of Michigan
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.

Dr. Wan is funded by the Wes Bradley, M.D. Memorial Grant.

+ Junhuang Zou, Ph.D.

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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.

Dr. Zou is the recipient of the C.H.E.A.R. endowment, created to support an annual Sensory-Neural Deafness Research Grant. C.H.E.A.R. (Children Hearing Education and Research) was absorbed into Hearing Health Foundation in 1991, and we are very proud to continue their legacy of funding research in sensory-neural deafness.