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 2021 Capita Foundation Auditory Research (CFAR) grant award recipients

Brian M. McDermott Jr., Ph.D.


Case Western Reserve University
Project Title: "Understanding and implementing the self-healing capacity of the auditory hair bundle for the treatment of hearing-impaired children in the US"

Hair cells are the cellular receptors for sound that reside in the inner ear. These cells are the epitome of cellular specialization to accomplish a specific biological task: mechanotransduction—the conversion of mechanical stimuli into an electrical response. These cells contain specific organelles on which hearing is dependent, including the stereocilia. The mechanosensitive hair bundle consists of a precise arrangement of actin-based stereocilia, which extend from the hair cell's apical surface. A systematic increase in stereociliary length results in a bevel-shaped hair bundle. Each cylindrical stereocilium is stiff, but its uniform girth tapers towards the base to allow for flexion. When sound enters the ear, it causes these tiny stereocilia to vibrate at high rates. Damage to the stereocilia is often the cause of hearing impairment. The damage can be caused by either loud noise or genetic mutations. In this grant, we will explore the self-healing capacity of the hair bundle and examine how it may be used for therapeutic approaches. 


Vibhuti Agrahari, Ph.D.


University of Oklahoma

Project Title:  "ROS-responsive NanoSensoGel for Prevention of Cisplatin-Induced Ototoxicity and Hearing Loss" 

Cisplatin-Induced Ototoxicity (CIO) and associated hearing loss is irreversible and there are no treatments currently available to reverse CIO, therefore, prophylactic care is critical. However, to reduce CIO, there is a need to identify the appropriate route of drug administration, and selection of an optimal drug delivery strategy with enhanced therapeutic efficacy, and the product translation to clinical application. This project will investigate the development of novel targeted nanoformulations to provide a prophylactic cure of CIO not only in adults but also in pediatric patients. The bio-responsive nanoformulations (Nano-SensoGel) will be designed to provide a long-term therapeutic effect through enhanced bio-retention and inner ear targeted attributes of the delivery system. The outcomes of this study will be critical in addressing the clinical needs towards the development of inner ear targeted technologies for the prevention of CIO-induced hearing loss.


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Announcing 2020 Capita Foundation Auditory Research (CFAR) grant award recipients

Alessia Paglialonga, Ph.D.

National Research Council of Italy (CNR); Institute of Electronics, Information Engineering and Telecommunications (IEIIT), Milan, Italy

Project Title: “Widespread Hearing Impairment Screening and Prevention of Risk (WHISPER)”

Project WHISPER will develop and evaluate a novel, web-based system to support widespread screening and prevention of hearing impairment. It will be the first system to combine: (1) remote speech recognition testing using an automated, language-independent speech-in-noise test, (2) assessment of the risk factors for developing hearing impairment via a language-independent, icon-based interface, and (3) modeling of the individual risk for developing hearing impairment and the associated cognitive decline using explainable artificial intelligence (AI). The project will help answer the need to increase access to screening and prevention (for older adults, for individuals in underserved areas, for minorities, and for those with low socioeconomic status). It will develop tools that are language-independent and natively designed to be delivered at a distance, e.g. via web or mobile app, and natively integrated with explainable AI to extract actionable knowledge from the measured data.


Daniel Q. Sun, M.D.

Johns Hopkins University School of Medicine

Project Title:  "Treatment of hearing loss using a novel magnetic nanoparticle gene delivery platform"

Currently gene therapy using adeno-associated viral vectors (AAV) has been successful in small mammals, but nearly 80% of all genes that are affected in genetic forms of hearing loss are too large to fit into AAV vectors found in humans. Thus, there is an unmet need for the development of alternative gene-delivery tools in the translational development of gene therapy for congenital hearing loss.  Successful completion of the aims in this proposal will provide a foundational understanding of Magnetic Nanoparticle (MNP) behavior in small animal models and accrue preclinical data to support the translational development of MNP technology for inner ear gene delivery. Leveraging this team’s experience in successfully bringing other inner ear therapeutics from the bench top to the bedside, we intend to similarly advance the translational development of MNPs into nonhuman primates and ultimately human clinical trials.


Mridula Sharma, Ph.D.


Macquarie University - Sydney, Australia 





Project Title:  "Effect of age and background noise on cortical EEG entrainment to natural conversation:  a preliminary study in adults with hearing loss"



This project addresses fundamental clinical and research needs in understanding how natural speech in a conversation is processed and perceived in complex listening situations and how this is affected by age in adults with hearing loss.  Therefore, the aims of this project are:
1. To assess and understand the mechanisms underlying speech perception in an innovative and more ecologically valid manner by using EEG and novel signal processing methods.
2. To delineate the effects of age on processing and understanding natural speech in noise.
3. To identify neural indices that could be used, in future clinical studies, as clinical measure of an individual’s ability to understand speech in the real world.
The outcomes will significantly advance knowledge in our understanding of the auditory processes that are required for older adults to understand natural speech. By including a clinical test population, the proposed project will provide the knowledge required for future development of clinical management protocols and strategies using speech tracking, thereby ensuring future clinical translation of the project outcomes.

The figure shows  EEG as recorded to the continuous speech and the continuous speech signal which is routed into the EEG amplifier. After the filtering and processing of the EEG and speech amplitude envelope, Temporal response function (TRF) is determined across all channels for the condition. Topographical maps of TRF at 100-150ms are also shown for the condition. 
The figure that shows the analysis from our pilot data


Soroush Sadeghi, M.D., Ph.D.


Center for Hearing and Deafness, State University of New York (SUNY) at Buffalo

Project Title: "Improving the vestibular nerve function by pharmacological manipulation of the inner ear"

The general aim of my research is to reach a better understanding of vestibular signaling and its modulation following compensation or adaptation and to find practical ways for enhancing vestibular compensation in humans.  This can be specifically useful for patients (e.g., after therapeutic vestibular neurectomy) or in conditions where unusual adaptation is required (e.g., space travel). 

Figure 1

Figure 1. Intra-labyrinthine injection and VsEP recordings.
  (A)Method of injection through the oval window. Note the exit point made on the anterior canal.  (B) Mouse’s head is attached to a linear shaker for VsEP recordings. 

In recent years, the traditional notion that peripheral end organs (i.e., hair cells and afferent terminals) in the inner ear are mere sensors has been challenged due to the presence of feedback (via an efferent pathway) from central areas. It has been shown that efferent inputs can modulate the activity of hair cells and afferents in vitro. The funding from Capita Foundation will be used to study the effect of the GABAergic and cholinergic efferent pathways on the response properties of the vestibular pathway.  Using an in vivo mouse model, we will use a method developed in our lab for intralabyrinthine injection (Fig. 1A) of different agonists and antagonists of relevant receptors and ionic channels and evaluate their effect on the vestibular nerve response by measuring the vestibular sensory evoked potentials (VsEP) (Fig. 1B). To find the behavioral correlate of the observed neuronal changes, we will measure the effect of intralabyrinthine injections of these drugs on the vestibulo-ocular reflex (VOR) – a reflex that functions to stabilize the eyes during head movements (Fig. 2).


Figure 2
Figure 2. Recording the VOR response in mice.   Eye movements will be recorded with an infrared camera in a head-restrained mouse. The mouse is rotated in the horizontal plane at different frequencies and velocities in the dark.  Right panel traces shows example eye movements during VOR response to head rotation.  


Results of the above studies could provide the means for designing new therapeutic approaches through local application of drugs in the inner ear, which could result in fewer adverse effects compared to the current systemic (e.g., oral) use of similar drugs in patients.


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Capita Foundation funding acknowledged in PLOS ONE research article

LoCHAid: An ultra-low-cost hearing aid for age-related hearing loss 

Article published by: Soham Sinha, Urvaksh D. Irani, Vinaya Manchaiah and M. Saad Bhamla


https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238922



Saad Bhamla, Ph.D.

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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.”