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NOBEL PRIZE 2026

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NIHNATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERSR01

Epigenetic mechanisms of cochlear damage and repair

Active
Institution
RUTGERS, THE STATE UNIV OF N.J., NJ
Principal investigator
Kelvin Y. Kwan
Funding
$652K
Duration
2025–2030
Open portfolio

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Abstract

PROJECT SUMMARY Pathogenic variants of human CHD4 cause Sifrim-Hitz-Weiss disease, a neurodevelopmental disorder associated with hearing loss. CHD4 is a chromatin-remodeling protein expressed in hair cells and supporting cells of the cochlea. We hypothesize that CHD4 maintains cell identity in the cochlea. We ablated CHD4 in hair cells and showed gradual hair cell degeneration along with epigenetic changes in supporting cells. Aim 1 tests if CHD4 ablation alters gene regulatory networks and changes hair cell identity to cause hair cell death. Aim 2 examines whether increased Wnt signaling changes the chromatin accessibility of supporting cells. Aim 3 investigates if CHD4 loss in supporting cells decreases DNA methylation at hair cell gene promoters to make supporting cell identity malleable. The proposal provides mechanistic insights into hair cell maintenance and regeneration, which can be repurposed to treat a wide spectrum of hearing loss.

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R01NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERSSpecial Emphasis Panel[ZRG1 ICN-A (02)]cochleaidentityhearing losscell identityhair cellshair cellcells aimhair

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