Liberman M. Charles
2022 FPA Scientific Grand Prize Laureate
Project status: active
The 2022 FPA Scientific Grand Prize is awarded to Prof. M. Charles Liberman for his pioneering work on the organization and function of the major nerve pathways connecting the inner ear to the brain. His discoveries concerning the role of auditory nerve fibers in hearing and hearing loss have changed our understanding of why tinnitus, hyperacusis and difficulty hearing in noise are so widespread in the aging ear and have charted a path towards the development of therapeutics to address these impairments.
Until recently, Liberman was Director of the Eaton-Peabody Laboratories at the Massachusetts Eye and Ear Infirmary, Boston, MA, USA. He is Harold F. Schuknecht Professor of Otology and Laryngology at Harvard Medical School and continues his research at the Eaton-Peabody Laboratories.
HIS RESEARCH
Prof. Liberman’s research has focused for more than 40 years on the inner ear, where the sensory cells, called hair cells, transduce sounds into electrical signals that are then carried to the brain by the fibers of the auditory nerve where they are processed. Following his thesis work on the effects of intense noise exposure on the inner ear, Liberman discovered that the auditory nerve in the normal ear was composed of three different types of fibers, which differ in their threshold sensitivity. They are recruited progressively, with low-threshold fibers activated first, in response to the weakest sounds, while those with high-threshold are only recruited by more intense sounds. This organization explains the remarkable dynamic range of the ear, which can function over an incredible range of sound pressure levels. The other key insight from this discovery was that the high-threshold fibers are particularly important in helping us hear in a noisy environment, when the low-threshold fibers are already driven to their maximum response levels by the background noise.
Synaptopathy, the “hidden hearing loss”: a new paradigm
Between 2009 and 2013, Liberman, with his colleague Prof. Sharon Kujawa, published a series of studies that changed our understanding of sensorineural hearing loss, the cause of the vast majority of hearing impairments in adults. Up to that point, hearing scientists believed that hair cells were the primary targets of damage, and that auditory nerve fibers were lost only after the hair cells died. Liberman and Kujawa showed that, actually, the auditory nerve fibers are the most vulnerable elements in both age-related and noise-induced hearing loss. Specifically, it is the tiny connections (i.e., synapses) between the nerve fibers and the hair cells that die first, leaving many surviving sensory cells partially disconnected from the brain. In experiments on mice, they showed that even a relatively mild noise exposure, causing only transient loss of hearing sensitivity, nonetheless destroyed up to 50% of these synaptic connections. This disease of the synapse or “synaptopathy”, as they called it, isn’t detectable on the audiogram – the gold standard audiological test - and therefore was dubbed “hidden hearing loss”.
These discoveries, further confirmed in humans by Liberman’s team, helped explain why difficulties hearing in a noisy environment are such a universal complaint of those with sensorineural hearing loss from a variety of causes. It has also suggested a novel way to think about the origins of tinnitus (ringing in the ears), in particular helping explain how it could be so common in people with normal audiograms.
Therapeutic developments for hidden hearing loss
Inspired by these new insights, and on research by many other groups into neural repair in other parts of the nervous system, Prof. Liberman started to work on synapse repair in the inner ear. In 2016, he showed that contacts between hair cells and nerve fibers could be regenerated after noise damage by local delivery of trophic factors called neurotrophins, proteins released by some cells in the normal inner ear to promote auditory nerve survival. Several biotech companies took Prof. Liberman’s patented work further to develop and test therapeutics to treat hidden hearing loss, with the promise of increasing hearing ability for millions of people.
Liberman’s work raises hopes too in improving the suffering of those with tinnitus or hyperacusis, because these distressing symptoms may arise from overcompensation in auditory brain circuits in response to the decreased outflow of neural activity from the inner ear caused by synapse loss.
Today, Prof. Liberman’s ongoing studies focus on the prevalence, diagnosis and development of therapeutics for hidden hearing loss in humans, with promise for many impactful discoveries yet to come !
HIS CAREER
Torn between his interest in science and his passion for music, Liberman decided, as an undergraduate at Harvard University, to combine them by studying how sounds are processed and perceived by the brain. His search for an introduction to hearing science led him to do an undergraduate reading course with Dr. Nelson Kiang, founding director of the Eaton-Peabody Laboratory of Auditory Physiology at the Massachusetts Eye and Ear Infirmary. He went on to do his doctoral thesis in Kiang’s Auditory Neurophysiology lab, obtaining his Ph.D. in Physiology from Harvard Medical School in 1976, and then spent two years in the laboratory of Dr. Sanford Palay receiving postdoctoral training in electron microscopy at the Harvard Medical School Department of Anatomy. In 1979, he was invited back to the Eaton-Peabody Laboratory (EPL) as an Assistant Professor in the Department of Otology (now the Department of Otolaryngology, Head and Neck Surgery) and has been there ever since, leading his own research group with continuous research funding from the National Institutes of Health. In 1996, he became Acting Director of EPL, and its Director in 1998. Over the past 26 years, he has overseen the expansion of the group and also has given his time, expertise, and guidance to promote a high standard of excellence across the center and the broader international hearing research community. He stepped down as Director in February 2022, to exclusively focus his efforts on research. In 2015 he co-founded Decibel Therapeutics™, a company aiming to develop treatments to restore and improve hearing and balance.
AWARDS AND HONORS
Liberman’s pioneering research has earned him a number of prestigious awards, including :
- 2002: McMahon Mentorship Award – HST Division of Harvard Medical School / MIT
- 2009: Award of Merit, Association for Research in Otolaryngology
- 2011: Carhart Award, American Audiological Society
- 2012: Bekesy Silver Medal, Acoustical Society of America
- 2018: Pioneers in Neuroscience Lectureship, SUNY Buffalo