# Ineffective wound healing responses enable chronic radiation-induced salivary gland dysfunction

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2020 · $350,672

## Abstract

Abstract:
More than 73% of head and neck cancer patients continue to suffer from the chronic consequences of
xerostomia months to years after the completion of radiotherapy making this one of the most compelling
issues in salivary gland biology. Despite technological advancements in cancer therapies, collateral
damage to salivary glands remains a significant problem for these patients and severely diminishes
their quality of life. The field of radiation-induced salivary gland damage is severely hampered by the
lack of a comprehensive model detailing the molecular stages of damage. The overall vision is to
restore salivary gland function in patients following radiotherapy by identifying healing stages in salivary
glands that lead to the stratification and administration of precise therapeutics for their stage. This
proposal will use the sequential phases of wound healing involving inflammation to its resolution and
reconstitution of tissue through proliferation and differentiation of epithelial tissue as steps to
accomplish this vision. We hypothesize that irradiated salivary glands fail to efficiently progress
through the wound healing phases leading to prolonged dysfunction. Our prior work has demonstrated
that radiation-induced proliferation in salivary glands is due in part to disruption of the PKCζ apical
polarity complex leading to enhanced nuclear localization of Yap, while models that restore salivary
function have repaired apical polarity and reduced nuclear localization of Yap. We propose to develop
a model that integrates each phase of wound healing detailing the interactions between phases and
the impact of nuclear Yap on the progression through these phases. The outcomes from this work
include: 1) inputs regulating sustained Yap nuclear translocation, 2) ability of chronic nuclear Yap to
prevent re-differentiation after IR, 3) when/if Yap is necessary for restoration of salivary gland function,
4) uncovering the interplay between wound healing phases that prevent restoration of salivary gland
function. Understanding this process would have a positive impact by revealing intervention points that
promote restoration of salivary gland function.

## Key facts

- **NIH application ID:** 10022119
- **Project number:** 5R01DE029166-02
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** KIRSTEN H LIMESAND
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $350,672
- **Award type:** 5
- **Project period:** 2019-09-20 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10022119

## Citation

> US National Institutes of Health, RePORTER application 10022119, Ineffective wound healing responses enable chronic radiation-induced salivary gland dysfunction (5R01DE029166-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10022119. Licensed CC0.

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