Lisa V. Goodrich, Ph.D.
Professor of Neurobiology
Harvard Medical School

Project: The Cellular and Molecular Substrates for Treating Hidden Hearing Loss

About 500 million people in the world suffer from some form of hearing loss, at an estimated cost of 750 billion dollars per year. Most hearing loss is caused by toxic drugs or exposure to excessively loud sound, and the disability increases with age. Even moderate noise exposure damages hearing, by disrupting synapses that connect receptor cells in the ear to neurons that send this information to the brain. However with multiple types of neurons carrying information to the brain and others carrying protective signals back to the cochlea from the brain, it is difficult to pick apart the roles of all these different neurons in noise-induced hearing loss.

In this project, Lisa Goodrich (HMS) will leverage a new suite of genetic tools to characterize how individual neuronal subtypes respond to acoustic trauma and to compare how potential treatments affect the fine details of cochlear wiring in animal models. Her laboratory will first focus on type 1c neurons that carry auditory information to the brain, and will assess effects of noise on both synapse number and gene expression. 1c neurons may be more sensitive to damage, and this work could explain why. They will then study two types of neurons that carry protective feedback signals from the brain, to understand how they change with noise exposure. Genetic silencing of one type will reveal whether it protects the cochlea from noise. Finally, they will explore how all of these different kinds of neurons respond to therapies based on two small proteins: Bcl-w, which protects synapses, and NT3, which promotes the formation of new synapses. Delivered in the right order and amount, these might prevent or even reverse noise-induced hearing loss, offering treatment to tens of millions of older Americans who have debilitating age-related hearing loss.