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Viral Gene Transfer

Our lab pioneered inner ear gene transfer, beginning nearly 20 years ago (Holt et al., 1999).  We continue to develop, innovate and discover viral vectors, promoters and DNA coding sequences for optimized delivery to the various cell types of the inner ear.  In a series of recent publications we used viral gene delivery to restore auditory function in models of human deafness.  In particular, we focused on the hearing loss genes TMC1 and USH1C.

Characterization of Stem Cell-Derived Inner Ear Organoids

In a series of collaborative experiments we have characterized stem cell-derived inner ear organoids.  We find that the the inner ear organoids, grown in a petri dish, develop sensory hair cells that resemble native inner ear hair cells.  These stem-cell derived hair cells could potentially be used for cell replacement therapies or, more immediately, as source for large numbers of cells for studies of gene expression and drug development. 

The Function of TMC Genes in Hair Cell Transduction

To understand the fundamental mechanism of how sensory hair cells convert mechanical information, such as sound or head movement, in electrical signals we have focused on the molecular components of the sensory transduction apparatus.  We identified TMC1 and TMC2 as critical components of the transduction machinery.  A series of papers and a growing body of evidence now support a prominent role for TMC1 and TMC2 as components of the sensory transduction channel in hair cells of mice and humans.

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If you have questions about these or any other projects please feel free to email
Jeff Holt ( or
Gwen Géléoc (
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