# Determining Sox10-mediated plasticity in irradiated salivary gland cells

> **NIH NIH F30** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $52,552

## Abstract

PROJECT SUMMARY/ABSTRACT
Therapeutic irradiation, a commonly used treatment for head and neck cancer patients, irreversibly damages the
salivary glands (SGs). Current therapies aim to alleviate the resulting xerostomia (dry mouth syndrome) but fail
to address the underlying mechanism of dysfunction, thus new strategies for tissue regeneration are needed.
Given that endogenous repair of irradiated SGs is majorly hampered due to the loss of saliva-producing acinar
cells and their progenitors, inducing the ability of the remaining ductal cells to behave as acinar progenitors (i.e.
plasticity) is an attractive repair strategy. Inducing plasticity is a complex process whereby transcription factors
often interact with chromatin modulators, such as Hdac1, to induce downstream gene regulators of progenitor
cell potency. Interestingly, it has been shown that some irradiated ductal cells can spontaneously revert towards
a progenitor-like state to enable acinar differentiation under severe stress conditions, although too few undergo
this transition to fully restore the gland. In order to enhance plasticity, we recently demonstrated that
overexpression of transcription factor Sox10 in non-irradiated ductal cells induces plasticity, allowing acinar
differentiation ex vivo. However, whether this set-up is applicable to irradiated ductal cells is unclear. Based on
preliminary data, we hypothesize that plasticity can be induced in irradiated ductal cells through overexpression
of Sox10, which activates a downstream regulatory network through binding with Hdac1. To prove this
hypothesis, our objectives are to evaluate the binding capacity of Sox10 to Hdac1, as well as the altered
downstream gene network and acinar formation capacity in irradiated cells after inducing a Sox10-mediated
plasticity. Overall, these data will then be used to formulate a new translational therapy in our in vivo radiation-
induced xerostomia animal model to aid in the repair of SGs post-radiation.

## Key facts

- **NIH application ID:** 10606665
- **Project number:** 1F30DE032585-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Christina Elizabeth-Rose Jones
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $52,552
- **Award type:** 1
- **Project period:** 2023-03-01 → 2027-03-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10606665

## Citation

> US National Institutes of Health, RePORTER application 10606665, Determining Sox10-mediated plasticity in irradiated salivary gland cells (1F30DE032585-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10606665. Licensed CC0.

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