University of Michigan
Investigating the role of Chd7 during noise-induced hearing loss

Mice born with loss of Chd7, the gene mutated in human CHARGE syndrome, exhibity middle ear defects and resistance to acoustic trauma. Preliminary results show that deletion of Chd7 in adult mice (using tamoxifen inducible Cre line) also results in variable resistance to acoustic trauma, even in the absence of middle ear defects. This suggests important functions for Chd7 in regulating hair cells and neuronal integrity in adult cochlea. The objective of this research is to identify how loss of Chd7 influences susceptibility to acoustic trauma in the mature cochlea.

Research area: noise-induced hearing loss (NIHL)

Long-term goal of research: to help identify novel genes and molecular pathways involved in protection from NIHL and provide rationale for designing new therapies.

University of Iowa
Misexpression of Neurog1 combined with delayed deletion of Atoh1 provides a novel model

Contemporary research is focusing on the regeneration of hair cells in hearing loss using Atoh1. Reconstitution of the organ of Corti requires proper organization of the two types of hair cells, inner and outer hair cells, as well as supporting cells. Recent data showed that level of Atoh1 determines the degree of survival of different types of hair cells. Jahan’s previous work demonstrated the survival of some organ of Corti-like cells without Atoh1 if replaced by a closely related transcription factor, Neurog1. It is now Jahan’s intent to investigate the effect of Atoh1 substitution with Neurog1 combined with a delayed loss of Atoh1 expression in viable animals. This combined mutant offers for the first time a critical test of presumed causalities of molecular mechanism that may regulate the patterning of the organ of Corti, including hair cell and supporting cell differentiation.

Research area: Hair Cell Regeneration

Long-term goal of research: To define the correct dose and duration of Atoh1 expression for type-specific hair cell development which will provide novel insights into hair cell regeneration.

Rochester General Hospital Research Institute
Differential Virulence gene expression of S. pneumoniae and Haemophilus influenzae in children with Acute Otitis Media & modulation of innate immune responses

Middle ear infections are the most common infectious disease among children leading to the use of antibiotics. Middle ear infections are typically followed by 4-12 weeks of middle ear effusion during which time children have diminished hearing leading to temporary delayed speech and language development. In developing countries, permanent hearing loss is not uncommon. Non-typeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae (Spn) are the two main bacteria that cause middle ear infections and are the target for new vaccine development. In the funded research, expression of various vaccine candidate proteins of NTHi and Spn in the nose (where middle ear infections start) and in the middle ear (where infections cause hearing loss) will be compared. Gene expression of the studied NTHi and Spn vaccine targets might be modulated by innate immunity of the host during disease progression and this too will be studied.

Research area: Middle Ear

Long-term goal of research: To develop a vaccine to prevent middle ear infections, thereby reducing hearing loss from this common childhood infection. Towards this goal here we will evaluate several vaccine candidates of the most common causes of middle ear infections to determine whether immunity induced by vaccination will be effective to rid the child of the bacteria when they reside in the nose and/or when they gain entry to the middle ear. We will also study how the gene expression of the studied vaccine targets might be influenced by the child’s immunity system.

Ravinder Kaur, Ph.D. is a Research Scientist at the Rochester General Hospital Research Institute. Kaur’s research focuses on the pathogenesis of middle ear infections and immune response of children to those infections with a goal of facilitating a vaccine to prevent hearing loss.

Click to download a PDF of Dr. Kempfle’s Meet the Researcher profile.

Purdue University
Influence of individual pathophysiology and cognitive profiles on noise tolerance and noise reduction outcomes

Listening to speech in noisy environments can be significantly challenging for people with hearing loss, even with help from hearing aids. Current digital hearing aids are commonly equipped with noise-reduction algorithms; however, noise-reduction processing introduces inevitable distortions of speech cues while attenuating noise. It is known that hearing-impaired listeners with similar audiograms react very differently to background noise and noise-reduction processing in hearing aids, but the biological mechanisms contributing to that variability is particularly understudied.

This project is focused on combining an array of physiological and psychophysical measures to obtain comprehensive hearing and cognitive profiles for listeners. We hope this approach will allow us to explain individual noise tolerance and sensitivity to speech-cue distortions induced by noise-reduction processing in hearing aids. With these distinct biological profiles, we will have a deeper understanding of individual differences in listeners and how those profiles affect communication outcomes across patients who are clinically classified with the same hearing status. This study’s results will assist in the development of objective diagnostics for hearing interventions tailored to individual needs.

Rutgers University
Identification of Transcription Factors for Hair Cell Regeneration

In mammals, when hair cells die from ototoxic drugs or loud noises, they are not replaced. Kwan’s efforts are focused on identifying transcription factors that promote repopulation and replacement of lost sensory hair cells. Transcription factors are DNA binding proteins that play crucial roles in global gene regulation. By repurposing transcription factors that are normally expressed during hair cell development, he plans to promote regeneration by controlled cell division to repopulate lost hair cells before differentiating nascent cells into hair cells.

Research area: hair cell regeneration

Long-term goal of research: To use a cocktail of small molecules that activates expression of transcription factors or their associated signaling pathways in order to promote functional auditory hair cell regeneration and alleviate hearing loss.

Washington State University Vancouver
Characterizing noise-induced synaptic loss in the zebrafish lateral line

Recent findings indicate that noise levels thought to be safe for auditory sensory hair cells may actually damage hearing at the level of peripheral auditory synapses. Little is known about this type of damage, which is usually not detectable using traditional audiograms and so has been dubbed “hidden hearing loss.” This project will study noise-induced hearing loss using zebrafish, where the auditory sensory cells are easily accessible and highly similar to those in humans, in order to uncover mechanisms of synaptic damage due to noise exposure. It will use a combination of techniques including immunohistochemistry and calcium imaging to directly examine the timing and extent of noise damage on peripheral auditory synapses.

Rockefeller University
Ascertaining the contribution of Piezo proteins to Mechano-transduction in Zebrafish hair cells

The proteins that mediate the transformation of mechanical forces into electrical signals within the sensory cells that convey the senses of hearing and balance have yet to be identified. This lack of knowledge has undoubtedly hindered the identification of therapeutic compounds capable of alleviating the complications that arise from disorders in hearing and balance, such as deafness and vertigo. Recently, a member of the novel piezo protein family has been shown to contribute to cutaneous mechano-sensation, raising the possibility that related family members may contribute to hearing and balance. Dr. Low will utilize the simple vertebrate commonly known as zebrafish, to address this possibility.

Research area: Fundamental Auditory Research

Long term goal of research: To identify therapeutic agents that can restore normal hearing and balance in individuals who have either lost these senses, or suffer from conditions caused by abnormal activity in the sensory cells that mediate them.

Sean Low Ph.D. received a B.S. in Cellular and Molecular Biology in 2001, and a Ph.D. in Neuroscience in 2008 from the University of Michigan. Desiring to focus on sensory transduction, Low sought out a postdoctoral position in the Saint-Amant lab at the University of Montréal from 2009 – 2011, where he examined the role of a Piezo protein in cutaneous mechano-transduction. These studies evolved into an interest in mechano-transduction processes in general, and a second postdoctoral position with Dr. Hudspeth at The Rockefeller University beginning in 2011.

New York University
A balancing act in hearing and vestibular loss: assessing auditory contribution to multisensory integration for postural control in an immersive virtual environment

Humans are surrounded by sensory information and need to select the most reliable ones in order to maintain balance and disregard input that might make us fall. This is called “weighting” and “reweighting” of sensory inputs. This project uses a virtual reality, head-mounted display (HMD) application to test balance with varying sensory cues, including visual, somatosensory, and auditory. With this application, an individual’s ability to weight and reweight visual and auditory information based on their head and eye movement and their postural sway can be identified. This method has been successfully used in prior studies to test responses to visual changes. The novelty of this project includes: the addition of auditory cues scaled to well-established visual cues; the measurement of head movement via the HMD; and the portability, simplicity, and affordability of the HMD system, which increases the likelihood of future clinical translation of this assessment. In this current pilot study, 12 individuals with unilateral sensorineural hearing loss will be compared with 12 individuals with unilateral peripheral vestibular hypofunction and with 24 healthy controls. Wearing the HMD, they will go through a series of postural tasks with several combinations of visual and auditory cues of two intensity levels while standing on either a stable floor (all somatosensory cues available) or a compliant foam (to reduce somatosensory input). Their postural sway and head movement responses to the stimuli will be calculated, and gaze patterns among the groups will be compared, along with exploring whether changes in eye position can explain changes in head movement.

University of Virginia
Susceptibility to chronic otitis media: translating gene to function

Each year in the United States, over $5 billion is spent on healthcare for inflammation of the middle ear (ME) known as Otitis Media (OM) in children. Some children develop chronic middle ear infections known as chronic otitis media with effusion and/or recurrent otitis media (COME/ROM). Our goal is to find genetic factors that increase risk for COME/ROM in children. The discovery of causal variants would increase knowledge of novel genes and pathways involved in COME/ROM pathogenesis.

Research area: Otitis Media; Genetics

Long-term goal of research: To improve the clinical prevention of chronic infections; therefore decreasing pediatric antibiotic use, surgery, and deafness.