# Enhancing Atoh1 function in hair cell regeneration

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2024 · $667,826

## Abstract

PROJECT SUMMARY
Sensorineural hearing loss is caused by the death of hair cells in the organ of Corti, and once lost, cochlear
hair cells in humans and other mammals do not regenerate. In contrast, non-mammalian vertebrates can
functionally recover from deafening injury by mobilizing supporting cells to divide and differentiate to replace
lost hair cells. Over the last 10 years, the consensus from many studies is that supporting cells in the
embryonic and neonatal organ of Corti retain a limited capacity to divide and differentiate into hair cells under
certain conditions, but that this ability declines precipitously prior to the onset of hearing.
One facet of such an age-dependent decline in regenerative potential is the function of the transcription factor
Atoh1. Ectopic expression of Atoh1 in embryonic or neonatal cochlear tissue can transform supporting cells or
adjacent non-sensory cells into hair cells - but this ability appears to be severely diminished after the onset of
hearing in mice. We have shown that additional hair cell transcription factors, such as Gfi1 and Pou4f3, can
enhance the ability of Atoh1 to generate hair cell-like cells in older animals, but it is not clear how closely these
resemble bona fide hair cells, whether reprogramming is feasible in ears that have been chronically deafened,
and whether additional interventions can improve the modest regeneration we observe. This proposal seeks to
evaluate the feasibility of transcription factor reprogramming in the mature, deafened cochlea. We will also
apply these cochlear regenerative strategies to the mature utricle, which we and others have shown to have a
greater capacity for regeneration than the cochlea, and also a better response to transcription factor
reprogramming.

## Key facts

- **NIH application ID:** 10889166
- **Project number:** 5R01DC014832-08
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Andrew K Groves
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $667,826
- **Award type:** 5
- **Project period:** 2015-12-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10889166

## Citation

> US National Institutes of Health, RePORTER application 10889166, Enhancing Atoh1 function in hair cell regeneration (5R01DC014832-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10889166. Licensed CC0.

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