Hearing Health Foundation (HHF)’s Hearing Restoration Project (HRP) is the first international research consortium focused on investigating hair cell regeneration as a cure for hearing loss and tinnitus.
The overarching principle of the HRP consortium is cross-discipline collaboration: open sharing of data and ideas. By having almost immediate access to each other’s data, HRP scientists are able to perform follow-up experiments much faster, rather than having to wait years until data is published.
Primary treatments for hearing loss have been hearing aids and cochlear implants. While these have been successful, they have limitations. Most people who have lost hearing have done so through noise damage or aging, and may be candidates for hair cell regeneration or restoration.
The HRP uses three different animal models for studying inner ear hair cell regeneration. Two of those models, the chick and zebrafish, show robust hair cell regeneration. If the hair cells of a chick or a fish are damaged, within a short time—only a day or two for the fish, a few weeks for the chick—new hair cells are formed. That’s a spectacular result, and it tells us that animals are capable of regenerating hair cells.
The mouse is our other experimental model. Like in humans, the mouse shows no hair cell regeneration; once damaged, hair cells are not restored. But if we use what we know about fish and birds to determine how to regenerate hair cells in the mouse, then we will be able to regenerate hair cells in people.
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+ STRATEGIC RESEARCH PLAN
PHASE 1 - DISCOVERY RESEARCH:
Compare the fish, chick, and mouse to discover pro- or anti-regeneration pathways and determine supporting cell fates.
So far, scientists have identified various pathways for hair cell regeneration. Since there are many potential gene targets, they continually utilize bioinformatics methods to winnow down and determine which are most relevant. Researchers have shown in the mouse neighboring supporting cells remain after deafening.
PHASE 2 - PATHWAY VALIDATION:
Verify animal model pathways and describe regeneration strategies.
Recent technological advances have enabled researchers to examine single hair cells rather than entire clusters. This aids our focus our study on gene expression immediately after a single hair cell is damaged. The question now being asked is, what are the early events that occur in the hair cells of zebrafish and chicks, but not in mice, before the hair cells die? The genes not undergoing the same expression in the mouse as in the other two animal models will be targets for manipulation.
PHASE 3 - DEVELOP TREATMENTS:
Identify drugs to trigger hair cell regeneration in mammals.
Experimental models from Phase 2 will be used to screen for drugs—using the mouse model first.
+ MEET THE CONSORTIUM
Peter Barr-Gillespie Ph.D.
Scientific Director, Hearing Restoration Project - Professor of Otolaryngology, Oregon Health & Science University
Studying mechano-electrical transduction by hair cells, the sensory cells of the inner ear.
John Brigande, Ph.D.
Associate Professor of Otolaryngology, Oregon Health & Science University
Developing methods to control gene expression in the inner ear; identifying genes critical for development of the ear.
Albert Edge, Ph.D.
Professor of Otolaryngology, Massachusetts Eye and Ear Infirmary, Harvard Medical School
Researching stem cells and the basic mechanisms of cellular repair in the nervous system; studying the loss of sensory cells in the inner ear that result in deafness due to excessive noise, drugs, disease, or aging.
Andy Groves, Ph.D.
Professor of Neuroscience, Baylor College of Medicine
Using the inner ear as a model system to address fundamental questions in developmental biology and regeneration; using chick embryology and mouse genetics to address these problems.
Stefan Heller, Ph.D.
Professor of Otolaryngology-Head and Neck Surgery, Stanford University
Developing solutions for reversing sensory hair cell loss in the mammalian cochlea using stem cell-based approaches.
Ronna Hertzano, M.D., Ph.D.
Assistant Professor of Otorhinolaryngology, Head & Neck Surgery, University of Maryland School of Medicine
Identifying targets for prevention of age and noise/ototoxic induced hearing loss and developing tools for sharing and presenting gene expression data.
Yehoash Raphael, Ph.D.
R. Jamison and Betty Williams Professor of Otolaryngology, University of Michigan
Determining how to restore hair cells and hearing in deaf guinea pigs by injecting into the inner ear a gene that triggers the growth of hair cells during embryonic development.
Neil Segil, Ph.D.
Research Associate Professor, Broad/CIRM Center for Regenerative Medicine and Stem Cell Biology, University of Southern California
Studying development aspects of cell cycle regulation in relation to the inner ear, hearing loss, and regeneration.
Jennifer S. Stone, Ph.D.
Research Professor of Otolaryngology-Head and Neck Surgery, University of Washington
Investigating cellular and molecular mechanisms guiding embryonic and post-embryonic production of sensory hair cells in birds.
+ SCIENTIFIC ADVISORY BOARD
HHF established a Scientific Advisory Board (SAB) to provide oversight and guidance to the HRP Consortium. The SAB comprises senior scientists in hearing science, regenerative biology, and related fields. This Board evaluates HRP projects for funding and monitors the performance of funded projects against the goals of the projects. Meet our SAB members below.
Bryan E. Crenshaw, Ph.D.
Children's Hospital of Philadelphia
Director of Basic Science Research, Division of Otolaryngology
Director of Basic Research, Center for Childhood Communication Scientist, Mammalian Neurogenetics Group
Adjunct Associate Professor of Otorhinolaryngology, Head and Neck Surgery, Perelman School of Medicine at the University of Pennsylvania
Lisa Goodrich, Ph.D.
Harvard Medical School
Professor of Neurobiology
David Ornitz, M.D., Ph.D.
Alumni Endowed Professor, Department of Developmental Biology Developmental Biology Program
David Pauls, Ph.D.
Massachusetts General Hospital
Professor of Psychiatry
Psychiatric & Neurodevelopmental Genetics Unit Center for Human Genetic Research
Edwin Rubel, Ph.D.
University of Washington
Department of Physiology and Biophysics, Department of Otolaryngology, at the Graduate Program in Neurobiology and Behavior, and the Virginia Merrill Bloedel Hearing Research Center at University of Washington
Doris Wu, Ph.D.
National Institute on Deafness and Other Communication Disorders
Chief, Section on Sensory Cell Regeneration and Development
Chief, Laboratory of Molecular Biology