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.