Hearing and Balance Restoration

Best Supporting Actors - In Your Ears?

By the University of Michigan Health System

This microscopic view of cells deep within the ear of a newborn mouse show in red and blue the supporting cells that surround the hair cells (green) that send sound signals to the brain. New research shows that the supporting cells can regenerate if damaged in the first days of life, allowing hearing to develop normally. This gives new clues for potential ways to restore hearing.     Credit: Guoqiang Wan, Univ. of Michigan

This microscopic view of cells deep within the ear of a newborn mouse show in red and blue the supporting cells that surround the hair cells (green) that send sound signals to the brain. New research shows that the supporting cells can regenerate if damaged in the first days of life, allowing hearing to develop normally. This gives new clues for potential ways to restore hearing.


Credit: Guoqiang Wan, Univ. of Michigan

There’s a cast of characters deep inside your ears -- many kinds of tiny cells working together to allow you to hear. The lead actors, called hair cells, play the crucial role in carrying sound signals to the brain.

But new research shows that when it comes to restoring lost hearing ability, the spotlight may fall on some of the ear’s supporting actors – and their understudies.

In a new paper published online first by the Proceedings of the National Academy of Sciences, researchers from the University of Michigan Medical SchoolSt. Jude Children’s Research Hospital and colleagues report the results of in-depth studies of these cells, fittingly called supporting cells.  

The research shows that damage to the supporting cells in the mature mouse results in the loss of hair cells and profound deafness. But the big surprise of this study was that if supporting cells are lost in the newborn mouse, the ear rapidly regenerates new supporting cells – resulting in complete preservation of hearing. This remarkable regeneration resulted from cells from an adjacent structure moving in and transforming into full-fledged supporting cells. 

It was as if a supporting actor couldn’t perform, and his young understudy stepped in suddenly to carry on the performance and support the lead actor -- with award-winning results.

The finding not only shows that deafness can result from loss of supporting cells -- it reveals a previously unknown ability to regenerate supporting cells that’s present only for a few days after birth in the mice.

If scientists can determine what’s going on inside these cells, they might be able to harness it to find new approaches to regenerating auditory cells and restoring hearing in humans of all ages.

Senior author and U-M Kresge Hearing Research Institute director Gabriel Corfas, Ph.D., says the research shows that supporting cells play a more critical role in hearing than they get credit for.

In fact, he says, efforts to restore hearing by making new hair cells out of supporting cells may fail, unless researchers also work to replace the supporting cells. “We had known that losing hair cells results in deafness, and there has been an effort to find a way to regenerated these specialized cells. One idea has been to induce supporting cells to become hair cells. Now we discover that losing supporting cells kills hair cells as well,” he explains.

“And now, we’ve found that there’s an intrinsic regenerative potential in the very early days of life that we could harness as we work to cure deafness,” continues Corfas, who is a professor in the U-M Department of Otolaryngology. “This is relevant to many forms of inherited and congenital deafness, and hearing loss due to age and noise exposure. If we can identify the molecules that are responsible for this regeneration, we may be able to turn back the clock inside these ears and regenerate lost cells.”

In the study, the “understudy” supporting cells found in a structure called the greater epithelial ridge transformed into full-fledged supporting cells after the researchers destroyed the mice’s own supporting cells with a precisely targeted toxin that didn’t affect hair cells. The new cells differentiated into the kinds that had been lost, called inner border cells and inner phalangeal cells.

“Hair cell loss can be a consequence of supporting cell dysfunctional or loss, suggesting that in many cases deafness could be primarily a supporting cell disease,” says Corfas. “Understanding the mechanisms that underlie these processes should help in the development of regenerative medicine strategies to treat deafness and vestibular disorders.”

Making sure that the inner ear has enough supporting cells, which themselves can transform into hair cells, will be a critical upstream step of any regenerative medicine approaches, he says.

Corfas and his colleagues continue to study the phenomenon, and hope to find drugs that can trigger the same regenerative powers that they saw in the newborn mice.

The research was a partnership between Corfas’ team at U-M and that of Jian Zuo, Ph.D., of St. Jude, and the two share senior authorship. Marcia M. Mellado Lagarde, Ph.D. of St. Jude and Guoqiang Wan, Ph.D., of U-M are co-first authors. Additional authors are LingLi Zhang of St. Jude, Corfas’ former colleagues at Harvard University Angelica R. Gigliello and John J. McInnis; and Yingxin Zhang and Dwight Bergles, both of Johns Hopkins University.

The research was funded by a Sir Henry Wellcome Fellowship, a Hearing Health Foundation Emerging Research Grant, the Boston Children’s Hospital Otolaryngology Foundation, National Institutes of Health grants DC004820, HD18655, DC006471, and CA21765; Office of Naval Research Grants N000140911014, N000141210191, and N000141210775, and by the American Lebanese Syrian Associated Charities of St. Jude Children’s Research Hospital.

The above post is reprinted from materials provided by University of Michigan Health System

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2011 Grant Recipients Announced

FOR IMMEDIATE RELEASE                                                                                                  
July 26, 2011                                                                                                                      

Contact:
Trisha Donaldson
212-257-6143
tdonaldson@drf.org
www.drf.org

DRF Increases grantmaking:  2011 Grant Recipients Announced

Deafness Research Foundation (DRF)’s National Hearing Health Grants Center is excited to announce that it has awarded over $600,000 to 25 outstanding research scientists in the field of hearing and balance science.  For two years in a row, we are excited to announce an increase in our grantmaking.

Each year, DRF awards research grants to young investigators who are exploring new avenues of hearing and balance science. These funds will support research in the following areas:

  • Fundamental Auditory Research – development, genetics, molecular biology, physiology, anatomy, and regeneration biology;

  • Hearing and Balance Restoration – infants, children and adults

    • cochlear implant, auditory hair cell regeneration, and auditory nerve regeneration;

  • Hearing Loss – aging, noise-induced, otosclerosis, ototoxicity, and otitis media;

  • Central Auditory Processing Disorder;

  • Usher Syndrome; and

  • Vestibular and Balance Disorders (dizziness and vertigo, Meniere's disease).

For this year's grants selection, DRF's Council of Scientific Trustees reviewed applications from scientists at renowned research institutions around the U.S.  The selected research projects received detailed peer review for scientific merit and program relevance.  A complete list of the 2011 grant recipients is provided below, including recipients whose research is funded in whole or part by the DRF Centurion Clinical Research Award, the C.H.E.A.R. Endowment Award, Collette Ramsey Baker Research Award, and The Todd M. Bader Research Grant of The Barbara Epstein Foundation, Inc.

FIRST YEAR HEARING & BALANCE RESEARCH GRANT RECIPIENTS
Keith E. Bryan, Ph.D., University of Iowa, Carver College of Medicine
Investigating the role of cabp1 in kcnq4 channel modulation

Brenton G. Cooper, Ph.D., Texas Christian University
Lateralization of acoustic perception in Bengalese finches

Regie Lyn P. Santos-Cortez, M.D., Ph.D., Baylor College of Medicine
Identification of genes that predispose to chronic otitis media in the at population of Bolabog, Boracay island, Philippines

Elizabeth Dinces, M.D., M.S., Albert Einstein College of Medicine
Effects of aging on selective attention in complex multi-source sound environments

Carolyn P. Ojano-Dirain, Ph.D., The University of Florida College of Medicine
Prevention of aminoglycoside-induced hearing loss with the mitochondria-targeted

Sung-Ho Huh, Ph.D., Washington University School of Medicine
Role of fgfs in cochlear sensory epithelium

Albena Kantardzhieva, Ph.D., Massachusetts Eye and Ear Infirmary
Defining the interaction partners of major proteins in the hair cell's synaptic ribbon

Shuh-Yow Lin, Ph.D., The University of California, San Diego School of Medicine
Molecular mechanisms of synaptic transmission in hair cells

Debashree Mukherjea, Ph.D., Southern Illinois University School of Medicine
Targeting inflammation in prevention and treatment of noise induced hearing loss

Erin K. Purcell, Ph.D., The University of Michigan, Kresge Hearing Research Institute
A stem cell-seeded nanofibrous scaffold for auditory nerve regeneration

Zlatka P. Stojanova, Ph.D., House Research Institute
Epigenetic regulation of the atoh1 gene

Jie Tang, Ph.D., Creighton University School of Medicine
Creation of a pendrin with both motor and transport functions

Ellen S. Wilch, Ph.D., Michigan State University College of Human Medicine
Identification of cis-regulatory gjb2 and gjb6 elements by chromosome conformation capture and investigation of potential cis-regulatory variants in persons with hearing loss and monoallelic mutation of gjb2

Hsiao-Huei Wu, Ph.D., The University of Southern California, Keck School of Medicine
Regulation of inner ear development by hgf, the nonsyndromic hearing loss gene, dfnb39

SECOND YEAR HEARING & BALANCE RESEARCH GRANT RECIPIENTS
Edward L. Bartlett, Ph.D., Purdue University
Cellular bases of temporal auditory processing

Soyoun Cho, Ph.D., Oregon Health & Science University
Dynamics of exo- and endocytosis at hair cells

Frances Hannan, Ph.D., New York Medical College
The role of diaphanous in the auditory cytoskeleton

Michelle Hastings, Ph.D., Rosalind Franklin University of Medicine and Science
Therapeutic correction of ush1c splicing in a mouse model of usher syndrome

Zhengqing Hu, M.D., Ph.D., Wayne State University School of Medicine
Innervation of in vitro-produced hair cell by neural progenitor-derived glutamatergic neurons

Judith S. Kempfle, M.D., Massachusetts Eye and Ear lnfirmary
Influence of bone morphogenetic protein 4 and retinoic acid on differentiation of inner ear stem cells

Neeliyath A. Ramakrishnan, Ph.D., Wayne State University School of Medicine
Molecular interactions of the hair-cell afferent synapse

DRF CENTURION CLINICAL RESEARCH AWARD RECIPIENT

James E. Saunders, M.D., Dartmouth Hitchcock Medical Center
Genetic hearing loss in remote Nicaraguan families

This research award is funded by the Centurions of the Deafness Research Foundation. DRF has partnered with CORE Grants Program of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) to offer a one-year DRF Centurion Clinical Research Award (CCRA) for clinical research in hearing and balance science.

DRF C.H.E.A.R. ENDOWMENT GRANT RECIPIENT

Patricia White, Ph.D., University of Rochester School of Medicine and Dentistry
1st year grant recipient
The role of foxo3 in hearing protection

The C.H.E.A.R. endowment was created to support an annual sensory-neural Deafness Research Grant. C.H.E.A.R. (Children Hearing Education and Research) was absorbed into DRF in 1991, and we are very proud to continue their legacy of funding research in sensory-neural deafness.

COLLETTE RAMSEY BAKER RESEARCH AWARD RECIPIENT

Kirill Vadimovich Nourski, Ph.D., M.D., University of Iowa Hospitals and Clinics
1st year grant recipient
Temporal processing in human auditory cortex
This research award is made in memory of Deafness Research Foundation’s founder, Collette Ramsey Baker.

THE TODD M. BADER RESEARCH GRANT OF THE BARBARA EPSTEIN FOUNDATION, INC., RECIPIENT

Marcello Peppi, Ph.D., Massachusetts Eye and Ear lnfirmary
2nd year grant recipient
Molecular mechanisms of dexamethasone-mediated protection from acoustic trauma
This research award is funded by The Todd M. Bader Research Grant of The Barbara Epstein Foundation, Inc.

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Deafness Research Foundation is the leading national source of private funding for research in hearing and balance science.  Research made possible by DRF grants has resulted in dramatic innovations that have increased options for those living with hearing and balance disorders, as well as protected those at risk.  Since our inception in 1958, we have awarded over $26.6 million through more than 2,000 scientific research grants to researchers who are dedicated to exploring new avenues of hearing and balance science.  With the potential of hearing restoration through regeneration biology, the scope of DRF-funded research has expanded enormously.  Since 1972, DRF has funded close to 40 research grants that have been instrumental in the development, evaluation and improvement of cochlear implants.  Approximately, 188,000 implant procedures have been completed worldwide with beneficial results, particularly when the procedure is undertaken in infants.  DRF also publishes the award-winning Hearing HealthMagazine.


www.drf.org
Voice (212) 257-6143 • Toll-Free (866) 454-3924 • TTY (888) 435-6104 • Fax (212) 257-6139

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