# Epigenetic mechanisms underlying the failure of hair cell regeneration in mammals

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2021 · $581,595

## Abstract

Project Summary/Abstract:
 Sensory hair cell regeneration does not occur spontaneously in the mature mammalian organ of Corti,
making hearing loss permanent. The goal of this proposal is to identify the causes and mechanisms behind the
failure of hair cell regeneration, as well as ways to stimulate regeneration in surviving populations of inner ear
supporting cells in deafened individuals. Our primary hypothesis is that regeneration requires the re-
engagement of developmental gene networks to guide supporting cells to a hair cell fate, and that during
postnatal inner ear maturation, epigenetic barriers arise that block the re-activation of these gene networks.
The goal is to develop methods to overcome these epigenetic barriers, and to establish new cell fates with
regenerative potential within the organ of Corti.
 Experimentally, perinatal mice retain a latent capacity for direct supporting cell transdifferentiation to a
hair cell-like fate, but this capacity is rapidly lost in the first weeks after birth. This age-dependent change in
regenerative potential provides a window through which to investigate the transition from a permissive to a
non-permissive state for this form of regeneration in the normally maturing organ of Corti. The work of this
proposal is to elucidate the mechanism(s) of epigenetic control of transdifferentiation in perinatal supporting
cells (Aim1) and to identify the machinery of maturation-related changes in epigenetic/chromatin structure in
supporting cells of the inner ear. (Aim 2). We hypothesize that these changes are responsible for the failure of
regeneration. Finally, to investigate the epigenetic structure of adult supporting cell chromatin in normal and
deafened mice (Aim 3). We hypothesize that manipulation of the epigenetic state is an important approach for
future regenerative medicine approaches to restoring lost hair cells.

## Key facts

- **NIH application ID:** 10200749
- **Project number:** 5R01DC015829-04
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** ANDREW P. MCMAHON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $581,595
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200749

## Citation

> US National Institutes of Health, RePORTER application 10200749, Epigenetic mechanisms underlying the failure of hair cell regeneration in mammals (5R01DC015829-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10200749. Licensed CC0.

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