Jeffrey R. Holt

Biosketch

Jeffrey R. Holt is a physiologist and neuroscientist focused on sensory transduction in auditory and vestibular hair cells of the inner ear. He earned a B.S. degree in Biology at Wofford College in Spartanburg, South Carolina. He then went to the University of Rochester where he received M.S. and Ph.D. degrees in the Department of Physiology with mentor Ruth Anne Eatock. After a Howard Hughes Medical Institute postdoctoral fellowship with David Corey at Mass General Hospital, he joined the Department of Neuroscience the University of Virgina for his first faculty position. In 2011 Dr. Holt was recruited back to Boston where he remains today as a Professor of Otolaryngology and Neurology at Boston Children’s Hospital and Harvard Medical School. He is widely recognized for his discovery of the sensory transduction channel in inner ear hair cells, TMC1, and has received the highest recognition within the field of auditory neuroscience including the Bellucci Prize, the Pioneer Award from the Association for Research in Otolaryngology and Scientific Grand Prize from the Foundation Pour L’Audition.

Research Interests

Dr. Holt’s research focuses on sensory transduction or the conversion of stimulus information into electrical information, the language of the brain. Sensory organs are at the interface between the world around us and the brain. Before we can understand how the brain processes information, we first need to understand how it collects and encodes information. As a model for sensory transduction the lab studies the sensory cells of the inner ear, known as hair cells. Dr. Holt's team aims to understand how sensory hair cells and neurons in the normal inner ear function. They want to identify the genes and proteins required for sensory transduction and identify why genetic mutations in those molecules cause dysfunction.

Using physiological techniques coupled with chemical-genetics the lab identified the protein that is key to auditory sensory transduction. The key protein is called Transmembrane Channel One or TMC1. TMC1 forms an ion channel or a small pore in the membrane that opens and closes in response to sound-induced vibrations in the inner ear. Unfortunately, pathogenic mutations in TMC1 can block its activity, thus causing genetic deafness.

Dr. Holt’s lab also focuses on development of therapeutic strategies to restore auditory function. The lab has pioneered use of viral vectors to deliver healthy DNA into deaf ears and demonstrated restoration of auditory function for several genes that cause profound deafness in humans, including TMC1. In some cases, the pre-clinical data show restoration of hearing with sensitivity to sounds as faint as a whisper.