Announcing 2022 Capita Foundation Auditory Research (CFAR) grant award recipients
Christopher Waterworth, Ph.D.
University of Melbourne, AUSTRALIA
Project Title: "Global
Audiology Baseline Needs Assessment"
This
research aims to summarize the current state and geographic variation of ear
and hearing care (EHC); specifically, we will survey providers globally to
assess the availability of infrastructure, including equipment, materials, and
ancillary services necessary to deliver care, facilitate training and
educational opportunities, and overcome barriers to ear and hearing care
service (EHC) delivery. EHC providers include the multidisciplinary care
team of ENTs (Ear, Nose and Throat Surgeons), audiologists, audiology
technicians, ENT clinical officers, hearing healthcare workers (village
healthcare workers trained in ear and hearing care), speech and language
therapists, teachers of the deaf and primary health care professionals with
specific audiology training. This is a complementary study to ongoing global
otolaryngology head and neck surgery (OHNS) and audiology workforce studies
which aim to capture the quantity and distribution of OHNS and audiology
providers in each country. Taken together, these studies serve as a baseline
needs assessment for audiology capacity on an international level, providing
novel data needed to inform interventions and policies. These international
studies have been developed by members of the Global OHNS Initiative, an
international collaborative of over 250 care providers, trainees, and students
from over 35 countries. This team has fostered discussion and mentorship across
institutional and national boundaries. Beyond the discrete research outputs
from this study, this study will facilitate research skill development for
trainees who may otherwise have limited opportunities for research involvement
and mentorship through their own institutions.
Pelin Koçdor,
MD
Başkent
University, Koç University, Istanbul, TURKEY
Project
Title: "An
attempt to show endolymphatic hydrops and its treatment in a
nitroglycerin-induced animal model of migraine"

Vestibular Migraine (VM) patients present with auditory
symptoms such as aural pressure, tinnitus, and sudden sensorineural hearing
loss. Half of Meniere’s Disease (MD) patients present with migrainous features,
such as a headache with photophobia or positive family history of migraine.
Moreover, about a quarter of VM and MD patients meet both diagnostic criteria.
So far, the MD’s pathophysiology remains unknown. Nevertheless, depending on
post-mortem temporal bone analyses, endolymphatic hydrops (EH) was noted as a
potential MD marker. Current migraine treatment options have shown success in
treating some of the patients with MD. In MD when medical treatment fails, the
recommendation is to use a second-line treatment, such as the intratympanic
injection of steroids. A third-line treatment could be either endolymphatic sac
surgery or the intratympanic injection of gentamicin, which has a higher risk
of hearing loss. The very last option is destructive surgical treatment
labyrinthectomy, with or without cochlear implantation. Since VM and MD
overlap, in a nitroglycerin-induced animal model of migraine, we may encounter
endolymphatic hydrops experimentally and try to reverse the effect of NTG with
migraine treatment. If our hypothesis is true; intractable Meniere’s disease’s
treatment options would change and there would be no more destructive treatment
methods like labyrinthectomy or intratympanic gentamicin injections and it
could be treated conservatively.
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.
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.
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.

