ABOUT DR. JEFFREY HOLT

Biography
Dr. Holt received his Ph.D. from the Department of Physiology at the University of Rochester in 1995. He then completed a postdoctoral fellowship with the Howard Hughes Medical Institute at Harvard Medical School, under the direction of David Corey. In 2001, Dr. Holt accepted a position working in the Neuroscience department at the University of Virginia. In 2011, Dr. Holt returned to Harvard to join the Department of Otolaryngology, the F.M. Kirby Neurobiology Center and the Neurobiology Program at Boston Children’s Hospital. In 2016, Dr. Holt became a professor of Otolaryngology and Neurology at Harvard Medical School. Currently, he also carries out research for the F.M Kirby Neurobiology Center and the Neurobiology program at Boston Children’s Hospital.

Research Interests
Dr. Jeffrey Holt’s current research is focused on the function and dysfunction of the inner ear. Dr. Holt studies sensory transduction, the conversion of stimulus information into electrical information. His labs seek to discover the ways in which sound is encoded and transmitted to the brain, adaptation in hair cells within the ear, and novel gene therapy strategies. His lab’s long term goal is to use this information to design novel therapeutic strategies aimed at restoring sensory transduction and inner ear function. Dr. Jeffrey Holt has published numerous articles and book chapters.

Harvard Medical School

Sensory transduction converts stimulus information into electrical information and is at the interface between the world around us and the brain. To understand how information is encoded and transmitted to the brain we study the sensory cells and neurons of the inner ear.

Sensory transduction in the ear begins with nanometer-scale movement of mechanosensitive organelles that project from the apical surface of inner ear hair cells. In the auditory system, this exquisite sensitivity can initiate signals that encode faint pizzicato from a classical violin. Remarkably, hair cells can also detect stimuli with amplitudes over a million times greater, and thus are able to signal the booming cannons of Tchaikovsky’s 1812 Overture as well. This extraordinary dynamic range is the result of a sensory transduction process that utilizes several feedback mechanisms to precisely reposition and tune the mechanosensitive apparatus within the optimal range, allowing detection of auditory stimuli that span the breadth of amplitudes and frequencies humans encounter daily.

Current projects in the lab range from investigations of sensory transduction and adaptation in hair cells, to development of inner ear function to development of gene therapy strategies for hearing restoration. To gain insight into inner ear structure and function we use electrophysiological techniques to study hair cells and neurons, molecular and genetic techniques to identify and manipulate inner ear genes and proteins, and imaging techniques to study protein localization and function.

We have an active research group focused on the function and dysfunction of the inner ear. Our goal is to understand how stimuli from the external world, such as sound, gravity and head movements are converted into electrical signals, how the information is encoded and how it is transmitted to the brain. We want to understand why genetic mutations cause hearing loss and vestibular dysfunction. We plan to use this information to design novel therapeutic innervations for deafness and balance disorders. Now, more than ever, there is remarkable opportunity for fundamental discovery in the basic neurobiology of the inner ear as well as opportunity to translate recent discoveries into real world strategies for treating hearing and balance disorders which affect ~250 million people worldwide.

Boston Children’s Hospital

We have an active research group focused on the function and dysfunction of the inner ear.  Our goal is to understand how stimuli from the external world, such as sound, gravity and head movements are converted into electrical signals, how the information is encoded and how it is transmitted to the brain. Furthermore, we want to understand why genetic mutations cause hearing and balance dysfunction.  We plan to use this information to design novel therapeutic innervations for deafness and balance disorders.

Sensory transduction in the ear beings with deflection of mechanosensitive organelles that project from the apical surface of inner ear hair cells.  The exquisite sensitivity of the auditory system can initiate signals that encode the faint pizzicato of a classical violin.  Remarkably, auditory hair cells can also detect stimuli with amplitudes over a million times greater, and thus can signal the booming cannons of Tchaikovsky’s 1812 Overture as well. This extraordinary dynamic range is the result of a sensory transduction process that utilizes several feedback mechanisms to precisely reposition and tune the mechanosensitive apparatus within the optimal range allowing detection of auditory stimuli that span the breadth of amplitudes and frequencies humans encounter daily.

Ongoing projects in the lab include the study of:

  • Mechanotransduction and adaptation in sensory hair cells
  • Firing properties of afferent neurons that relay information to the brain
  • Development of inner ear function
  • Novel gene therapy strategies to treat inner ear dysfunction