Ronna Hertzano

Headlines in Hearing Restoration

By Yishane Lee

The cornerstone of Hearing Health Foundation for six decades has been funding early-career hearing and balance researchers through its Emerging Research Grants (ERG) program. Many ERG scientists have gone on to obtain prestigious National Institutes of Health (NIH) funding to continue their HHF-funded research; since 1958, each dollar awarded to ERG scientists by HHF has been matched by NIH investments of more than $90. Within the scientific community, ERG is a competitive grant awarded to the most promising investigators, and we’re always especially pleased when our ERG alumni who are now also members of or affiliated with our Hearing Restoration Project consortium make headlines in the mainstream news for their scientific breakthroughs.

Hair cells in the mouse cochlea courtesy of the lab of Hearing Restoration Project (HRP) member Andy Groves, Ph.D., Baylor College of Medicine.

Hair cells in the mouse cochlea courtesy of the lab of Hearing Restoration Project (HRP) member Andy Groves, Ph.D., Baylor College of Medicine.

Ronna Hertzano, M.D., Ph.D. (2009–10): Hearing Restoration Project consortium member Hertzano, an associate professor at the University of Maryland School of Medicine, and colleagues identified a gene, Ikzf2, that acts as a key regulator for outer hair cells whose loss is a major cause of age-related hearing loss. The Ikzf2 gene encodes helios, a transcription factor (a protein that controls the expression of other genes). The mutation of the gene in mice impairs the activity of helios in the mice, leading to an outer hair cell deficit.

Reporting in the Nov. 21, 2018, issue of Nature, the team tested whether the opposite effect could be created—if an abundance of helios could boost the population of outer hair cells. They introduced a virus engineered to overexpress helios into the inner ear hair cells of newborn mice, and found that some mature inner hair cells became more like outer hair cells by exhibiting electromotility, a property limited to outer hair cells. The finding that helios can drive inner hair cells to adopt critical outer hair cell characteristics holds promise for future treatments of age-related hearing loss.

Patricia White, Ph.D. (2009, 2011), with Hearing Restoration Project member Albert Edge, Ph.D.: White, a research associate professor at the University of Rochester Medical Center, Edge, a professor of otolaryngology at Massachusetts Eye and Ear and Harvard Medical School, and team have been able to regrow the sensory hair cells found in the mouse cochlea. The study, published in the European Journal of Neuroscience on Sep. 30, 2018, builds on White’s prior research that identified a family of receptors called epidermal growth factor (EGF) that is responsible for activating supporting cells in the auditory organs of birds. When triggered, these cells proliferate and foster the generation of new sensory hair cells. In mice, EGF receptors are expressed but do not drive regeneration of hair cells, so it could be that as mammals evolved, the signaling pathway was altered.

The new study aimed to unblock the regeneration of hair cells and also integrate them with nerve cells, so they are functional, by switching the EGF signaling pathway to act as it does in birds. The team focused on a specific receptor called ERBB2, found in supporting cells. They used a number of methods to activate the EGF signaling pathway: a virus targeting ERBB2 receptors; mice genetically altered to overexpress activated ERBB2; and two drugs developed to stimulate stem cell activity in the eye and pancreas that are already known to activate ERBB2 signaling. The researchers found that activating the ERBB2 pathway triggered a cascading series of cellular events: Supporting cells began to proliferate and started the process of activating other neighboring stem cells to lead to “apparent supernumerary hair cell formation,” and these hair cells’ integration with the network of neurons was also supported.

This was prepared using press materials from the University of Maryland and the University of Rochester. For more, see hhf.org/hrp.

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On a Data-Driven Mission

By Peter G. Barr-Gillespie, Ph.D.

The annual meeting of Hearing Health Foundation’s (HHF) Hearing Restoration Project was held in Seattle November 11-12, 2018. We used this meeting to update one another on recent progress on HHF-funded projects, discuss in detail the implications of new data, evaluate the directions of ongoing projects, and plan for the next funding period.

As you may recall, in November 2016 the Hearing Restoration Project (HRP) made a deliberate turn toward funding only the highest-impact science that our group leads the world in researching—we have termed this the “Seattle Plan.” We therefore devoted a substantial portion of our efforts to cross-species comparisons that contrast molecular responses to inner ear sensory hair cell damage in species that regenerate their hair cells, especially chickens and fish, with responses in mice, which like other mammals do not regenerate their hair cells. We also have been examining the “epigenetic” structure of key genes in the mouse, as one hypothesis is that epigenetic modifications of the DNA—that is, the inactivation of genes through chemical changes to the DNA—causes mouse (and human) cells of the cochlea to no longer respond to hair cell damage by regenerating hair cells.

Avian and mammal supporting cell subtypes differ, but Stefan Heller, Ph.D., and team are investigating if an evolutionary homogenous equivalent exists in the organ of Corti, and if this knowledge could be used for hair cell regeneration. Credit: Chris Gralapp / Otolaryngology Head and Neck Surgery (OHNS) - Stanford University School of Medicine

Avian and mammal supporting cell subtypes differ, but Stefan Heller, Ph.D., and team are investigating if an evolutionary homogenous equivalent exists in the organ of Corti, and if this knowledge could be used for hair cell regeneration. Credit: Chris Gralapp / Otolaryngology Head and Neck Surgery (OHNS) - Stanford University School of Medicine

I am happy to report that progress over the past two years on these two major projects has been outstanding. For the cross-species comparisons, Stefan Heller, Ph.D., and Tatjana Piotrowski, Ph.D., reported on single cell analysis of, respectively, chick and fish hair cell organs responding to damage. Using single cell analysis—isolating hundreds to thousands of individual cells and quantifying all of the protein-assembly messages they express—we can determine the molecular pathways by which hair cells are formed during development and regeneration. This approach has always been promising, but this year we have begun to reap the expected benefits, as those projects have given us an unprecedented view of hair cell formation.

The epigenetics project overseen by Neil Segil, Ph.D., has now reached maturity, and using the voluminous data acquired over the past several years his lab has shown how supporting cells (from which we intend to regenerate hair cells) change the epigenetic modification of their DNA so they no longer are able to switch on key genes used for turning them into hair cells. A topic of great interest at the meeting was that of genetic reprogramming: Can we use genes (like transcription factors, proteins that control the transfer of genetic information) or small molecules (which often can be taken orally and still reach their targets) to overcome the epigenetic modification and push supporting cells to turn into hair cells? Preliminary results from Segil’s lab and from others in the field make us optimistic that the reprogramming approach will eventually be part of a regeneration strategy.

We also heard from Seth Ament, Ph.D., a bioinformatics expert we recently recruited to the HRP to explicitly compare our various datasets and find the common threads between them. Ament has used gene expression data from the chick, fish, and mouse, as well as the epigenetic data from the mouse, to hypothesize which genes may be important for hair cell regeneration. As a systems biology specialist, Ament brings a fresh eye to the field of auditory science and has not only identified some of the genes we expected to be important, but new ones as well. His success nicely justifies our cross-species approach, and the bioinformatics comparisons that he has been able to achieve in his initial HRP project have been impressive.

Finally, two other Seattle Plan projects have gone well, including our data-sharing platform called the gEAR (gene Expression Analysis Resource), developed by Ronna Hertzano, M.D., Ph.D., which allows us to analyze our data privately but also to efficiently share data with the public. In addition, John Brigande, Ph.D., reported on his project developing mouse models for testing interesting new genes; his group will be adding several powerful models in the year to come.

The excitement at the meeting extended to our future plans. We agreed that the Seattle Plan was the still the proper course, and we eagerly anticipate more data and results to come from our consortium of researchers. We are truly getting a clearer picture of hair cell regeneration due to the HRP’s efforts. That said, there is a long way to go; our efforts show us how surprisingly intricate biology is, despite knowing from the start that systems like the inner ear are remarkably complex. Nature always has surprises for us, by turns dashing treasured hypotheses while revealing unexpected mechanisms. The HRP is most definitely on track for success, and all of us in the HRP sincerely thank you for your continued support.

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HRP scientific director Peter G. Barr-Gillespie, Ph.D., is a professor of otolaryngology at the Oregon Hearing Research Center, a senior scientist at the Vollum Institute, and the interim senior vice president for research, all at Oregon Health & Science University. For more, see hhf.org/hrp.

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HHF Attends HLAA 2018 Convention

By Nadine Dehgan

I was fortunate to attend my very first Hearing Loss Association of America (HLAA) Convention last week in Minneapolis, MN with Hearing Health Foundation (HHF)’s Program Associate, Maria Bibi.

Nadine Dehgan and Maria Bibi at HLAA 2018.

Nadine Dehgan and Maria Bibi at HLAA 2018.

We spent much of our time serving as resources to the highly engaged attendees. In the exhibit hall at our HHF booth, we answered questions related to our critical research and awareness programming. Maria and I were humbled to learn of the deep appreciation for our work from our booth’s visitors.

Several educational sessions were held beyond the exhibit hall. I was particularly grateful to witness John Brigande, Ph.D., and Ronna Hertzano, M.D., Ph.D., speak about HHF’s Hearing Restoration Project (HRP), the international scientific consortium dedicated to identifying better treatments and cures for hearing loss and tinnitus. Here, I met a supporter of HHF, who said, “[Drs. Brigande and Hertzano] were both informative, encouraging, and enthusiastic about their work and the possible outcomes. I will continue to follow their progress even more closely now.”

HHF Emerging Research Grants (ERG) 2018 recipient Evelyn Davies Venn, Au.D, Ph.D, also delivered a compelling presentation. An Assistant Professor at the University of Minnesota, Dr. Venn’s research focuses on a highly personalized hearing technology to help individuals better understand speech in noise. She discussed a new hearing aid in concept phase that will convert the sense of touch into sound electricity.

A shift from typical days in our quiet New York City office, the four-day convention connected us with many inspirational people—folks with hearing loss and scientists alike. Buzzing with energy, optimism, and knowledge about hearing loss, the convention was an important representation of how HHF’s work impacts so many individuals.

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Women’s History Through the Lens of HHF

By C. Adrean Mejia

Before Women’s History Month concludes, Hearing Health Foundation (HHF) would like to highlight the accomplishments of women in science, technology, engineering, and mathematics (STEM), including those who have been instrumental to our own progress toward preventing, treating, and curing hearing loss and related conditions.

Historically, STEM has been majority male, but the growing inclusion of women in the industry is closing the gender gap. In fact, LinkedIn reports the percentage of women entering STEM roles in the last four decades is greater than that of any other professional sector. In 1978, the STEM workforce was only 10% female, while today about a third of this field is comprised of women.

Emerging Research Grants (ERG) recipient Dr. Wafaa Kaf administers a hearing screening. Credit: Missouri State University.

Emerging Research Grants (ERG) recipient Dr. Wafaa Kaf administers a hearing screening. Credit: Missouri State University.

As individuals and as an organization that values inclusiveness, we all at HHF applaud the trend of growing opportunity for women in scientific professions, while remaining equally grateful to the male researchers and Board members who offer their commitment, support, and expertise. Our founder was a woman; 60 years ago, Mrs. Collette Ramsey Baker began a quest to find better treatments and cures for hearing and balance conditions which is championed by all today.

We would like to acknowledge the outstanding women on HHF’s Board of Directors, whose altruism and intelligence have furthered hearing research and HHF’s growth. Our Board Chair, Elizabeth Keithley, Ph.D., who has been an auditory researcher for more than 30 years, began her association with HHF as a grant reviewer. Dr. Keithley has conducted and published a number of studies related to the mechanisms of inflammation and aging on the inner ear.

From left: HHF Board Chair Elizabeth Keithley, Ph.D., and Board member Judy Dubno, Ph.D.

From left: HHF Board Chair Elizabeth Keithley, Ph.D., and Board member Judy Dubno, Ph.D.

Board member Judy Dubno, Ph.D., professor at the Medical University of South Carolina, is considered one of the most important otolaryngology researchers in the nation. Her work has focused on auditory perception, hearing loss, and speech recognition. Dr. Dubno was also a contributor to the report that successfully urged the FDA to create a category of over-the-counter hearing aids to make hearing loss treatment more accessible to American adults.

Also serving on the Board is Ruth Anne Eatock, Ph.D., of the University of Chicago, who studies sensory signaling by hair cells and neurons in the inner ear. She was recently published in The Journal of Neuroscience for her investigation of inner ear sensory cells in rodents.

HHF is also thankful for the three female scientists who are part of our Hearing Restoration Project (HRP) consortium working to permanently cure hearing loss: Ronna Hertzano, M.D., Ph.D., Tatjana Piotrowski, Ph.D., and Jennifer S. Stone, Ph.D. Their labs at the University of Maryland, Stowers Institute for Medical Research, and the University of Washington, respectively, have uncovered valuable insights related to a biological cure for hearing loss.

Our Emerging Research Grants (ERG) program has empowered many brilliant, female researchers, including those recently published: Wafaa Kaf, Ph.D., researching new techniques to diagnose Ménière's disease; Michelle Hastings, Ph.D., investigating early genetic intervention for Usher syndrome; Elizabeth McCullagh, Ph.D., examining the connection between sound localization difficulties and Fragile X Syndrome; and Samira Anderson, Au.D., Ph.D., working to improve hearing aid fit to enhance usage.

Finally, we are fortunate to have Nadine Dehgan serving as our CEO. Ms. Dehgan plays a crucial role in our growth and programming efficiency, and her leadership experience and passion for how hearing science can better people’s lives has made her a strong fit to drive HHF forward.

HHF deeply values the work of all individuals who bring us closer to a world without hearing loss and tinnitus. For Women’s History Month, we’re honored to call special attention to the women who have been part of these life-changing efforts in the spirit of Mrs. Ramsey Baker, whose determination and selflessness still inspires us today.

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San Diego Tunes In to Hearing Health

By Jordan Conole

On February 11th, Hearing Health Foundation (HHF), the nation’s largest nonprofit funder of hearing and balance research, hosted a public seminar on hearing health and hearing loss in at the Central Library in Downtown San Diego.

Guests mingle before the start of presentations on hearing loss research and treatments in the Shiley Special Events Suite of the San Diego Central Library.

Guests mingle before the start of presentations on hearing loss research and treatments in the Shiley Special Events Suite of the San Diego Central Library.

Event attendees included members of the public, scientists and researchers, many of whom have devoted their careers to finding a cure for hearing loss.

Ronna Hertzano, M.D., Ph.D., a surgeon at the University of Maryland Medical Center, spoke about the need for change in the way we treat hearing loss, noting, “Just as a doctor would now take a patient with elevated or slightly higher blood pressure seriously, we must do just the same with hearing.” Dr. Hertzano claimed that those who experience hearing loss oftentimes can suffer from loneliness and feelings of isolation.

According to a recent study by the National Aging Committee, more than 11% of those with some form of hearing loss suffer from depression compared to only 5% of the general public.

Dr. Harrison Lin, a scientist funded by HHF’s Emerging Research Grants program, and colleagues discovered that of the 48 million Americans who report experiencing some form of hearing loss, only about one-third of those actually seek out treatment.

Ken Knoblett, a San Diego resident who counts himself as part of that third, noticed a drastic change in his interactions with friends and family once he began to use hearing aids. “I was immediately able to be more connected to my friends and family and enjoy gatherings again. The hearing aid and treatment really changed my life for the better!”

Based on the strong connection to hearing loss and its strong emotional side effects, testing for hearing loss and treating it is the best way to combat and prevent its underlying side effects.

Hearing loss is an isolating condition for hundreds of thousands of Americans, but the scientists working for HHF hope to someday end that isolation.

Jordan Conole is a freelance journalist who covers San Diego local nonprofits and charity events in the surrounding areas. 

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You’re Invited: Comprehensive Hearing Health Experience in February 2018

By Lauren McGrath

In honor of our 60th anniversary, Hearing Health Foundation (HHF)’s Board Chair, Elizabeth Keithley, Ph.D., is hosting Hearing360—an educational and social forum at the San Diego Central Library—in early 2018. Hearing360 seeks to engage HHF’s San Diego area constituents with the latest updates in hearing research and everyday guidance for hearing health.

Featured event speakers include scientists Ronna Hertzano, M.D. and Andy Groves, Ph.D. from HHF’s Hearing Restoration Project (HRP), the world’s first international consortium dedicated to identifying a permanent biological cure for hearing loss. Their individual presentations on the regeneration of hair cells in the inner ear will be followed by a brief Q&A session.

Ronna Hertzano, M.D.

Ronna Hertzano, M.D.

Andy Groves, Ph.D.

Andy Groves, Ph.D.

Hearing360 will also honor the generosity of longtime HHF supporters Frank and Chris De Francesco, who shared their experiences raising a child with profound hearing loss in “Why We Believe in Hearing Health Foundation,” which appeared in the Fall 2017 issue of Hearing Health magazine.

Scheduled for Sunday, February 11 from 3:00 - 5:00 PM in the San Diego Central Library’s Shiley Special Event Suite, Hearing360 will be fully accessible with a t-coil loop system and open captioning. Light refreshments and wine will be available.

Limited space is available and an RSVP is required for all guests. We look forward to meeting you in San Diego. Please contact HHF at events@hhf.org with any questions regarding Hearing360.

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