videoCapita
Research Overview

Capita Foundation is a nonprofit organization that funds hearing research scientists with micro-grants to innovate. Our seed grants encourage researchers to think outside the box and explore fearlessly in prevention and cure of hearing disorders. Over the past decade of micro-grants our Capita awardees have averaged a 10 fold return with subsequent [NIH, NSF, etc] funding.

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CAPITA FOUNDATION - NEWS and EVENTS





Announcing 2019 Capita Foundation Auditory Research (CFAR) grant award recipients

Prof. Karen Avraham

Tel Aviv University

Project Title: "Gene therapy in a mouse model of human hearing loss DFNB76"

Adeno-associated virus (AAV) has become very popular in the gene therapy field in recent years, and several proof-of-principal studies in the field of hearing loss have demonstrated its potential for treatment of genetic deafness. AAV has major advantages for gene therapy. Most importantly, AAV appears to elicit no immunological response in humans and recombinant AAV is also almost entirely incapable of integration, which enhances its safety. Several synthetic AAVs have been engineered to transduce cells in the inner ear with high efficiency and have been used to demonstrate rescue of auditory and vestibular function in deafness mouse models.  We hope our efforts will lay the groundwork for future development of gene therapy in humans. In addition, we hope this work will contribute to the understanding of the roles of nesprin proteins in cellular processes in general, and specifically in outer hair cell physiology.



The point of no return? These outer hair cells are in excellent form, arranged in three rows, just a day before they start deteriorating due to an absence of the gene SYNE4. Alterations in the DNA sequence of the SYNE4 gene leads to deafness in children and adults. Models are being used to test methods of gene therapy, in order to rescue hearing due to defects in the SYNE4 gene.


Credit: Shahar Taiber, MD-PhD student

Karen Avraham - Genomics of Deafness laboratory, Tel Aviv University





Valeriy Shafiro, Ph.D.

Rush University


Project Title:  "Validation of the Basic Auditory Skills Evaluation (BASE) 


battery for internet home testing of cochlear implant listeners"



Accessible internet-based auditory testing can have a wide reach beyond the typical clinical settings and empower people with cochlear implants to take more active roles in monitoring their progress and rehabilitation. This project will evaluate a comprehensive online battery of tests in three general areas of auditory function: basic spectro-temporal processing, nonlinguistic meaningful sounds, speech perception in quiet and in noise. The results will provide a basis for further developing and implementing easily accessible and affordable online diagnostic tests and online auditory training programs for people with hearing loss.






Joseph C. Toscano, Ph.D.

Villanova University

Project Title:  "Improving speech recognition for listeners with auditory neuropathy"



Our research examines effects of hearing difficulty on speech perception, a problem that affects many adults even if they have normal hearing thresholds. These cases of "hidden hearing loss" can result in problems coding intensity differences at higher sound levels  and, in turn, can disrupt perception of certain acoustic cues used to distinguish speech sounds. This project will investigate a new technique to improve speech recognition by filtering the sound signal to make these intensity differences more salient, compensating for deficits associated with hidden hearing loss.


Saad Bhamla, Ph.D.

Georgia Tech University

Project Title: “The LoCHAid: A low-cost, open-source hearing aid for Age Related Hearing Loss”




Victor Wong, Ph.D.

Burke Neurological Institute

Project Title: "TARGETING α-TUBULIN AND MIRO ACETYLATION TO 

ENHANCE NEURITE OUTGROWTH IN SPIRAL GANGLION NEURONS"

  My long-standing research interests lie in identifying molecular mechanisms for axonal regeneration after nervous system disease or injury. Axons in the adult nervous systems have little capacity to regenerate after injury. Although hearing regenerative capacity have been documented in avian and amphibian species, the reversal of hearing loss in mammals has been a persistent challenge. Although most therapeutic strategies have focused on the replacement of hair cells (HCs); there also is a need to address the subsequent degeneration of the innervating spiral ganglion neuron (SGN) for functional recovery of hearing. Moreover, very little is known about how to promote SGN neurite growth. There is, therefore, a critical and unmet need to determine how to enhance SGN peripheral neurite growth. The focus of my research is to examine how post-translational modifications can change the fate of SGN neurite growth. Specifically, the main objective is to understand how acetylation of microtubules, which affect microtubule stability, and acetylation of Miro, a mitochondrial transport protein, can impact SGN neurite growth under pathological conditions. Ultimately, I wish to capitalize these biological processes (i.e., microtubule dynamics and axonal transport) into therapeutic strategies to encourage neural regeneration and repair.




Dr. Amineh Koravand
University of Ottawa



Project Title:  “Investigating the Temporal Resolution Capacity in School Aged Children via Neurophysiological Measurement. Pilot Study.”

Prof. Koravand's research deals with the relationship between the peripheral and central auditory systems in children. Her goal is to develop neurophysiological measures (biological markers) to assess the central auditory functions of children during early childhood, to prevent disorders while brain plasticity is still significant.


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Announcing 2018 Capita Foundation Auditory Research (CFAR) grant award recipients




Daniel A. Llano, M.D., Ph.D.


University of Illinois at Urbana & Champaign


Project Title:  “An exercise intervention to prevent aging-related hearing loss in a mouse model.”




In our research program, we will examine the impact of aging on the auditory system. We will focus on developing innovative approaches to measure metabolic changes in the aging auditory system and developing novel interventions to mitigate them. Successful completion of this work will lead to new approaches to preserve hearing as we age.



Josée Lagacé, Ph.D. and Benoît Jutras , Ph.D.

University of Ottawa

Project Title:  "Virtual Reality For Auditory Training Therapy: A Pilot Study"


Virtual reality (VR) allows an individual to interact in real time with a three-dimensional, computer-simulated environment. The objective of this pilot study is to evaluate VR as an effective interface for ensuring uptake and motivation to auditory training in children with auditory processing difficulties. Since many children with auditory processing difficulties also have learning problems at school, this approach could also contribute to the enhancement of their learning experience and as well as to a reduction of schooling failure.





Madhu Sundarrajan, Ph.D.

University of the Pacific

Project Title:   Audiological and Communication Outcomes in Children with Unilateral Hearing Loss: A Pilot Study.”


Unilateral hearing loss (UHL) or single-sided deafness is a type of hearing impairment where individuals have typical hearing in one ear and impaired hearing in the other ear. Permanent UHL exists when the average pure tone air conduction threshold at 0.5, 1, and 2 kHz is greater than or equal to 20 dB HL or pure tone air conduction thresholds are greater than 25 dB HL at two or more frequencies above 2 kHz in the affected ear with an average pure tone air conduction threshold in the good ear less than or equal to 15 dB (National Workshop on Mild and Unilateral Hearing Loss 2005). It is estimated that 1/3 of children with hearing loss are diagnosewith UHL (Lieu, 2018).


Historically UHL was typically not treated in children with the presumption that the contra-lateral ear with hearing levels within the typical range will suffice in providing adequate acoustic stimuli for development of speech perception and communication skills (Oyler, Oyler & Matkin, 1987). However, recent research has shown that children with untreated UHL have poorer communication and academic outcomes compared to typical hearing (TH) children (Kishon-Rabin, Kuint, Hildesheimer, & Ari-Even, 2015, Fitzpatrick et al., 2018; Lieu, 2018), indicating that children with UHL may benefit from an amplification device fitted to the poorer ear.
This project aims to ameliorate the critical gap in the literature by comprehensively investigating audiological and communication outcomes in children with UHL. Furthermore, this project will provide vital information regarding clinical recommendations for children with UHL, in order for them to maintain age appropriate auditory, communication and academic outcomes.

Matthew J. Wilson, Ph.D.
Northern Illinois University


Project Title:  Relationship Between Cognitive Changes and Speech-in-Noise Deficits in Individuals with a History of Concussion: An Efferent System Study.” 


It is well known that long-standing cognitive deficits in the areas of attention and memory frequently accompany concussion. The role that these cognitive deficits play in the development of auditory processing difficulties, such as trouble understanding speech in noise (SIN), following injury remains unclear. Processing auditory information requires a complex interaction between afferent and efferent auditory pathways. The nature of the relationship is such that afferent information, which travels from cochlea to cortex, can be modulated by top-down, cortical influences via feedback loops in the efferent system (ES). These loops are integral for a variety of auditory skills, like understanding SIN. ES strength can be non-invasively measured using a technique known as otoacoustic emission (OAE) suppression, which quantifies how well outer hair cell activity is suppressed in the presence of noise. Greater levels of suppression are indicative of stronger ES activation and have been shown to correlate with better auditory comprehension abilities.
The interdependence of the cortex and efferent pathway suggests that alterations in cortical activity, like what is seen following concussion, may have an impact on overall suppression levels and, by default, play a role in the development of SIN difficulties; however, the nature of the relationship remains poorly understood. Thus, this study aims to examine the relationship between electrophysiological indices of cognition and SIN abilities and how those relate to changes in behavioral performance. Finding will not only improve audiological diagnosis, treatment, and rehabilitation options, but will also expand the role of the audiologist in the area of head injury research.


Philippe Vincent, Ph.D.

Johns Hopkins School of Medicine

Project jointly funded with Hearing Health Foundation
https://hearinghealthfoundation.org/

Project Title:   Investigating mechanisms of degeneration of ribbon synapses between auditory inner hair cells and type 1 afferent nerve fibers after noise trauma in mammals.”


During all of our life, we are surrounded by sounds that include different frequencies and intensity levels. In the inner ear, the sensory hair cells pick up the sound signal and transmit it to auditory nerve fibers via chemical synapses by releasing the transmitter glutamate; and auditory nerve fibers transmit the sound-coding signal to the brain.

Sound intensity is encoded by the amount of glutamate released by the hair cell, leading to glutamate receptor activation and then action potential firing in auditory nerve fibers. During noise exposure, it has been described that auditory nerve fiber endings can be damaged short- or long-term, most likely due to and excess of calcium influx into the auditory nerve fiber endings. This phenomenon is called excitotoxicity, however, the underlying mechanisms are not completely understood.  

Here I propose to investigate molecular mechanisms of synaptic transmission between hair cells and auditory nerve fibers and to test how they are affected after noise trauma.

Valerio Magnaghi, Ph.D.

University of Milan

Project Title:  “Unrevealing mechanisms of Schwann cell in vestibular schwannoma and their impact on hearing loss.”


Vestibular Schwannoma is a benign tumor of the acoustic nerve causing hearing loss. It arises from Schwann cells, the main myelin-forming cells in the nerve. Thus, changes in the oncogenic properties of these cells may be involved in hearing loss.

The main goal of our project is to analyze the molecular mechanisms underlying the human Schwann cells oncogenic transformation, potentially responsible of the vestibular schwannoma onset, and their vulnerability to environmental electromagnetic fields, that in principle might be pathologically relevant for the hearing loss.

Saad M. Bhamla, Ph.D.

Georgia Tech University

Project Title:  A low-cost, open-source and self-fitting hearing aid.”  





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Announcing 2017 Capita Foundation Auditory Research (CFAR) grant award recipients

Alisha L. Jones, Au.D., Ph.D., CCC-A

Auburn University




Project Title:  “The effects of auditory training on acceptable noise levels”


Acceptable noise levels have been found to assist in predicting potential success with hearing aids. If we can find a way to lower a person’s acceptable noise level, then their potential for success with hearing aids might increase. This project will examine the effects of three different computer-based aural rehabilitation programs on acceptable nose levels in adults with hearing loss.






Jacopo M. Fontana, Ph.D.

Karolinska Institutet, Stockholm, Sweden


Project Title:  Gender Differences to Noise Trauma in the Mouse Cochlea Abstract”



Project Description:
The overall goal of my project is to study the effect of sex hormones on hearing loss due to noise in female mice.

Noise induced hearing loss is a permanent hearing impairment common in our society resulting from prolonged exposure to high levels of noise. Recent findings demonstrated that the circadian rhythms plays an important role in modulating auditory sensitivity to noise trauma. Mice day-exposed to noise recovered to normal hearing thresholds compared to the nigh-exposed ones. This diurnal variation demonstrates the result of strict interaction between hormones like glucocorticoids and the circadian cochlear clock. Sex hormones like estrogen have also a circadian regulation but most of the published studies on noise-induced hearing loss (NIHL) used male only even if NIHL affects both men and women. Therefore, a new study is needed to better explain the effect of sex hormones on hearing loss due to noise in females to better understand the potential role of estrogen receptor signaling in the auditory system. 




Victor Wong, Ph.D.


Burke Medical Research Institute

Project Title:  "Microtubule Dynamics and Microtubule-Based Transport in Spiral Ganglion Neurons"

My long-standing research interests lie in identifying molecular mechanisms for axonal regeneration after nervous system disease or injury. Axons in the adult central and peripheral nervous systems have little capacity to regenerate after injury. Although hearing regenerative capacity have been documented in avian and amphibian species, the reversal of hearing loss in mammals has been a persistent challenge. Most therapeutic strategies have focused on the replacement of hair cells (HCs); however, HC replacement has been largely ineffective since subsequent degeneration of the innervating spiral ganglion neuron (SGN) peripheral neurites severely compromises efforts for functional recovery of hearing. Both the success of cochlear implants (CI) and of future therapeutic approaches critically depend on the integrity of SGNs and the availability of functional neurites for direct stimulation. Moreover, very little is known about how to promote SGN neurite growth. There is, therefore, a critical and unmet need to determine how to enhance SGN peripheral neurite growth. The neuronal processes contain a network of cytoskeletal structures necessary to steer neurite outgrowth and maintain structural integrity. Such structures comprise of actin and microtubules that are under the influence of extrinsic cues, thereby affecting their stability, dynamics, and the ability to re-direct neurite growth. Moreover, changes in actin and microtubule dynamics have been implicated to impact transport of important cargoes such as mitochondria and mRNAs in the neuronal processes. These biological processes are necessary to re-establish proper innervation and circuit assembly. Therefore, the main objective of my research is to understand 1) how changes in microtubule dynamics affect neurite growth under pathological conditions, 2) how axonal transport is regulated by microtubule stability, and 3) how to capitalize these biological processes (i.e., microtubule dynamics and axonal transport) into therapeutic strategies to encourage neural regeneration and repair.

Dunia Abdul-Aziz, M.D.


Massachusetts Eye and Ear Institute


Project Title: Generation of Inner Ear Organoids and ATOH1 – Reporter to Study Hair Cell Differentiation"


Loss of inner ear hair cells is the predominant cause of hearing loss. High throughput screening of drug libraries for compounds that may promote hair cell regeneration has until now been precluded by the relatively few number of cells that can be derived from the mammalian cochlea.  Our lab has recently established a protocol for expansion of inner ear progenitor cells in culture, thereby generating “inner ear organoids” which can be used to study pathways in inner ear development. 


We propose to design an Atoh1-reporter system in which the regulatory elements of the key hair cell- fate determining gene, Atoh1, drive luciferase signal.  Delivery of this reporter into inner ear organoids allows us to directly study, in a high throughput fashion, the regulation of Atoh1 in primary hair cell progenitors. We propose to use this organoid-based reporter system to test the effects of candidate genetic /epigenetic  modifying drugs on Atoh1 activity. This will serve as one of potentially several applications of this reporter system in drug and genetic screening.



Dr. Andrew Wise


Bionics Institute, Melbourne, Australia







Project: Drug delivery to the cochlear for synaptic repair
The Problem: Most adult people, including you and I, are likely to have damaged the highly sensitive sensory cells in our inner ear (see image). We will be disappointed to learn from our doctor that there are no therapeutic options to treat this damage and that unfortunately our condition is likely to worsen over time. There is desperate need to develop drug therapies that can treat, or possibly reverse hearing loss.
Project Aims: We have developed a novel way to deliver medication to the inner ear using specially designed particles that are made using nanoengineering techniques. In order to develop this system for use in the clinic we need to test their effectiveness in delivering medication into the inner ear. Therefore, the aim of this project is to measure the levels of medication inside the inner ear following delivery using the particle system. Outcomes of this study will be critical in further developing the technology so that it can be used to treat hearing loss in the clinic.




A primary cause of hearing loss is damage to the sensory cells in the inner ear – the hair cells and neurons that are responsible for detecting and transmitting sound information to the brain. What we are beginning to understand is that the sensitive connections (red dots – arrow) between the sensory hair cells (blue cell) and the neurons (green cells) are highly susceptible to damage. We are developing drug therapies to ‘reconnect’ the cochlea to treat hearing impairment.

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PLOS ONE publication by Valeriy Shafiro, Ph.D.
Capita Foundation is pleased to announce that Valeriy Shafiro, Ph.D., who was awarded a grant from us in 2012 for a research project titled, "Environmental sound and speech perception in relation to language development in children with cochlear implants," has recently published a research report in PLOS ONE. 

Link to report:  http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0167030

We congratulate Valeriy and all his contributors for the exceptional work.

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Announcing 2015 Capita Foundation Auditory Research (CFAR) grant award recipients

Amanda Lauer, Ph.D.

Johns Hopkins University, Dept. of Otolaryngology


  




Project Title: “Optimizing hearing with top-down brain control of the ear.”  





Project Description

The overall goal of my research is to understand how auditory input from the ear affects the brain, and how the brain in turn affects the ear through efferent feedback loops. I am particularly interested in understanding the hearing disorders that develop when input to and from the brain is altered. We propose to study top-down efferent effects on hearing to understand how the brain controls the ear using optogenetic, behavioral, and immunohistochemical techniques in rodent models. Understanding how these pathways work may open up new treatment avenues for hearing disorders and will help us understand how hearing is optimized by top-down brain control of cochlear activity.


Medial (MOC) and lateral olivocochlear (LOC) neurons project from the brain to the ear and control information sent back to the brain. Adapted from Lauer et al. (2012). Neurobiology of Aging.


Sanjee Abeytunge

The Rockefeller University

Project Title:  "A Novel Micro-probe for Direct Stimulation of Cochlear Hair Cells




The ear is the fastest and most sensitive sensory organ in the human body. It can resolve data a thousand times faster than the eye and can detect vibrations in the environment at the atomic-scale. The dynamic range of human hearing embraces up to 120 dB of sound-pressure level (SPL). This dynamic range allows humans to hear a millionfold range of amplitudes. The frequency response of a human ear extends to 20 kHz while other mammals, such as whales and bats, can hear up to hundreds of kilohertz. However, the current stimulation probes of hair cells in the cochlea, the sense organ of the ear, to study the mechanics of the inner ear is limited to less than 1 kHz. This limitation leaves most of the mammalian auditory frequencies unstudied. This experimental limitation is due to the physical dimensions of the probes and their configurations used during experiments. My work is design and construction of a micrometer scale novel probe that will overcome the current frequency limitation.