# Epigenetic Therapy to Treat Radiation-induced Xerostomia

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $433,906

## Abstract

ABSTRACT
 Most head-and-neck cancer patients receiving radiotherapy treatment develop life-long adverse effects.
Side effects presented as hyposalivation and chronic xerostomia result from radiation damage to nearby
salivary glands. Limited palliative options are currently available for these patients, reinforcing the need for
regenerative therapies. Our regenerative efforts, using non-viral gene therapy to overexpress water channel
Aquaporin-1 (AQP1) in radiation-surviving salivary gland epithelial cells, showed restorative results by
increasing salivary flow into the oral cavity. However, as both viral and non-viral vectors are restricted by the
ability to provide long-term expression, a next generation of AQP1 therapy that results in sustained gene
expression awaits.
 Our preliminary data demonstrates that methylation of the endogenous AQP1 promoter in epithelial cells is
an important mediator of gene expression. In addition, the methylation status alters after exposure to radiation.
Based on these findings, we hypothesize that epigenetic altering of the AQP1 promoter in radiation-surviving
epithelial cells facilitates a change towards sustained endogenous AQP1 expression. To test this hypothesis,
we adapted a new CRISPR method and aim to (1) demonstrate the negative correlation between the level of
methylation and AQP1 expression, and (2) develop in vitro and in vivo methods to optimally alter the
methylation level of the AQP1 promoter in irradiated epithelial cells.
 These studies bring in vivo epigenetic editing to a reality as a means of modulating endogenous gene
expression and sustained water movement in damaged salivary glands. As a result, this continuous production
of salivary flow can resolve xerostomia in radiated head-and-neck cancer patients in a long-term setting.

## Key facts

- **NIH application ID:** 10498489
- **Project number:** 1R01DE032014-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Isabelle M.A. Lombaert
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $433,906
- **Award type:** 1
- **Project period:** 2022-07-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10498489

## Citation

> US National Institutes of Health, RePORTER application 10498489, Epigenetic Therapy to Treat Radiation-induced Xerostomia (1R01DE032014-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10498489. Licensed CC0.

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