# Developing novel stem cell-based epigenetic approaches to treat hearing loss

> **NIH VA I01** · JOHN D DINGELL VA MEDICAL CENTER · 2022 · —

## Abstract

Project Summary
Auditory hair cells are mechanotransduction receptors that convey sound signals to the brainstem via spiral
ganglion neurons (SGNs). However, hair cells are vulnerable to a number of insults, including noise, blast,
aging, and traumatic brain injury. Adult mammalian hair cell loss is usually irreversible, causing permanent
hearing loss and other inner ear disorders. Currently, there are no biological approaches to replenish human
hair cells. The long-term goal of this project is to use stem cell-based approaches to regenerate the damaged
auditory system to treat hearing loss and other inner ear disorders. In this proposal, we will generate human
sensory hair cells and rebuild hair cell-SGN connections using a stem cell-based epigenetic approach.
We have identified human utricle epithelia-derived prosensory-like cells (HUCs) that exhibit features of
prosensory cells. We found that HUCs demonstrated genomic DNA methylation in a pilot study. We applied the
DNA methyltransferase (DNMT) inhibitor 5-azacytidine (5-aza) to HUCs and found that treated HUCs
expressed hair cell genes and proteins. Therefore, in this proposal we hypothesize that the DNMT inhibitor 5-
aza induces HUCs to differentiate into new functional hair cells that can replace damaged hair cells and form
synapses with auditory neurons. To test this hypothesis, three specific aims are proposed:
Specific Aim 1: Define the induction of HUCs into sensory hair cells by 5-aza.
Specific Aim 2: Investigate the integration and synapse formation of 5-aza-treated HUCs in vitro.
Specific Aim 3: Determine the survival, differentiation, integration, and function of 5-aza-treated HUCs in vivo.
In this proposal, we will generate human sensory hair cells and rebuild hair cell-neuron connections using a
stem cell-based epigenetic approach. The advantage of an epigenetic approach is that expression and
phenotype of gene are heritably changed, whereas their DNA sequences remain constant. The long-term aims
of this work are (a) to discover and explore innovative regeneration approaches to improve the health and
welfare of military personnel and veterans with hearing disturbances, and (b) to accelerate the transition of
stem cell technologies into new standards of care to treat hearing loss and other inner ear disorders. Success
of this work will significantly promote the research of stem cell-based hearing regeneration, which will
potentially affect the state of medical science in today’s battlefield experience on function, wellness, and overall
quality of life for veterans as well as their caregivers and families.

## Key facts

- **NIH application ID:** 10293594
- **Project number:** 5I01RX002100-05
- **Recipient organization:** JOHN D DINGELL VA MEDICAL CENTER
- **Principal Investigator:** Zhengqing Hu
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-12-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10293594

## Citation

> US National Institutes of Health, RePORTER application 10293594, Developing novel stem cell-based epigenetic approaches to treat hearing loss (5I01RX002100-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10293594. Licensed CC0.

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