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Oregon Hearing Research Center scientists make big discoveries in tiny inner ear

Many faculty members studying the auditory system have hearing loss

Dr NuttallImagine devoting a career to something five nanometers in length – an unimaginably small-sized molecule found in only 10,000 to 15,000 mammalian cells. Add the fact that this molecule is encased in the hardest bone in the body, and one begins to understand the challenge of identifying the makeup of hair cells in the inner ear. It’s a challenge taken on by Peter Gillespie, PhD, Professor, Department of Otolaryngology, Head & Neck Surgery, and it’s something he knows will keep him busy throughout his career.

“I was trained as a biochemist, and when I was a post-doc, people would say, ‘You can’t do biochemistry on hair cells. It’s impossible,’” said Dr. Gillespie. “It’s very challenging, but on the other hand, I like a good challenge.”

Dr. Gillespie is not alone in his drive to understand the auditory system and its connections to hearing loss. He and colleagues that make up the Oregon Hearing Research Center, led by Director Alfred Nuttall, PhD, are undaunted by the challenges of their chosen field. Auditory neuroscience research involves understanding the structure of the complex inner ear and how our brains translate its signals into everyday hearing.

Some of the basic science research underway at OHRC may not develop into clinical treatments for years or decades to come, but the prevalence of hearing loss reinforces the need for such work. One in 10 Americans has hearing loss, and that number – 36 million – is expected to nearly double by 2030.

From the time he joined OHSU in 1996, Dr. Nuttall, Professor, Department of Otolaryngology, Head & Neck Surgery, has helped build a team of faculty members who make up one of the most prestigious, well-funded research centers of its kind in the world; each researcher has at least one National Institutes of Health grant, and he himself has two grants, each with more than 32 years of continuous funding. Inadvertently, Dr. Nuttall has also amassed one of the largest groups of scientists with hearing loss doing research on the subject.

“When I came out for my first interview with [Dr. Nuttall], he noticed my hearing aid and said, ‘You have hearing loss,’” said John Brigande, PhD, Associate Professor, Department of Otolaryngology, Head and Neck Surgery, who joined OHRC in 2003. “And I said, ‘I do. I have severe to profound sensorineural hearing loss.’ Strangely enough our shared hearing loss was a nice ice breaker.”

Several OHRC faculty members have hearing loss, and this personal connection with the very science they study has implications for how they interact and the research they conduct. Lina Reiss, PhD, Assistant Professor, Department of Otolaryngology, Head and Neck Surgery, is embarking on a longitudinal study to compare how cochlear implants and hearing aids work in tandem to assist hearing. Her first subject is none other than her colleague Dr. Brigande, who received a cochlear implant earlier this year as a patient in the OHSU cochlear implant program.

“My hypothesis is that the brain doesn’t like having multiple inputs that sound different,” said Dr. Reiss. “I have preliminary data that show when people listen through a cochlear implant over several months or years their pitch perception changes. This is consistent with anecdotal reports from patients who say voices through the implant sound squeaky, child-like or like Mickey Mouse at first, but later sound normal.”

None of the OHRC researchers point to personal hearing loss as the primary motivation in their work, but the connection does impact their professional lives. “My hearing loss is one reason I’m focusing on combining electric and acoustic hearing and trying to preserve hearing,” said Dr. Reiss. “Personally, I thought about getting the Hybrid cochlear implant but the risks are not low enough right now that I would do it.”

Cochlear implants are surgically implanted devices that allow individuals with severe to profound hearing loss to have access to sound. Hybrid cochlear implants are designed to preserve hearing and be used with a hearing aid in the same ear. Recent research has shown there are positive effects to combining the use of a cochlear implant with a hearing aid; each device offers separate benefits in pitch perception and speech recognition.

Dr. Lina Reiss OHRC researchers are also investigating the prevention of hearing loss – be it genetic, noise-induced or drug-induced. Approximately 80 percent of premature babies in neonatal intensive care units in the US are given gentamicin, for example. This, and other aminoglycoside antiobiotics, is known to be ototoxic – or damaging to the ear. Peter Steyger, PhD, Associate Professor, Department of Otolaryngology, Head and Neck Surgery, knows the consequences of ototoxic antibiotics because he was given them as an infant when he had meningitis. “If I didn’t have streptomycin, I would have died,” he said. “These are life-saving drugs, which is why they’re still used so much.

“What my lab is interested in is determining how the drugs get across the blood-labyrinth barrier and into the cochlea,” Dr. Steyger said. “Because once drugs kill the sensory cells in the cochlea, you’re deaf.” Dr. Steyger’s is one of very few labs in the world focusing on the trafficking of ototoxic drugs across the blood-labyrinth barrier that protects the inner ear (like the blood-brain barrier protects the brain) to prevent drug-induced hearing loss.

Dr. Brigande’s work focuses on the genes involved in development of the mammalian inner ear. The hope is that misexpression of one or more of these genes could be therapeutic and restore auditory or vestibular function in the diseased inner ear. Mammals, unlike birds, amphibians and reptiles, have lost the ability to regenerate sensory cells.

When he joined the OHRC, he presented a research proposal of “unconventional and risky science,” but Dr. Brigande said his ideas were embraced even as a junior faculty member. “The folks here always do things differently. [My mentors] were comfortable with the risk, which says a lot about the kind of scientists we encourage here at OHSU and OHRC specifically.”

That spirit of innovation and collaboration pervades the work of the OHRC, with the reminder that, as Dr. Steyger said, “the auditory system ties you to everybody that you interact with” – a credo taken from everyday experience.

Pictured: (Top) Dr. Alfred Nuttall is Director of the Oregon Hearing Research Center, one of the most prestigious, well-funded centers of its kind; (Bottom) Dr. Lina Reiss guides colleague and study subject Dr. John Brigande through a hearing exercise in her research lab.

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