# Elucidating the Mechanisms of Salivary Gland Dysfunction Following Gamma-Irradiation Utilizing an Experimental and Computational Approach

> **NIH NIH F31** · UNIVERSITY OF ROCHESTER · 2022 · $47,552

## Abstract

Individuals diagnosed with head and neck cancer undergo radiation therapy as a standard treatment. However,
in the process of using radiation therapy to shrink the tumor, the salivary glands are inadvertently and irreversibly
damaged. This damage manifests as a loss of saliva secretion, occurs rapidly without marked cell death, and
leads to deleterious effects, including loss of taste, oral infections, and xerostomia (dry mouth). The mechanism
by which this early loss of function occurs, is currently unknown and presently there is little in the form of
treatment, with most options being palliative. Thus, there is a pressing need to expand our understanding of
salivary gland physiology and the effects of γ-irradiation on both the structure and function of the salivary gland.
This proposal utilizes experimental techniques including confocal, Stimulated Emission Depletion (STED) and
intravital microscopy. Each technique will be employed for use in a variety of assays to investigate the structural
and functional consequences of acute γ-irradiation on salivary glands. This in vitro and in vivo experimental
approach will additionally be used in combination with computational modeling through a long-term collaboration
to understand in detail the effect of γ-irradiation on secretion. In an iterative manner, experimental data will be
input to the computation model and subsequently used to make further predictions which will be experimentally
tested- furthering our understanding of physiology and pathology of salivary glands. In these studies, this
experimental-computational approach will be used to determine how alterations within the salivary gland impact
its function, leading to dry mouth, and an eventual permanent loss of glandular tissue and function. This proposal
addresses three different mechanisms that may dictate this loss of function. These include an alteration in
functioning of gap and tight junctions, calcium signaling, and mitochondrial bioenergetics. By examining each of
these aspects, the experimental data can be integrated into the computational model. The great utility of this
approach is that many iterations of computational experiments can be completed in parallel with these in vitro
and in vivo studies and used to suggest further experiments and make predictions. The dynamic utilization of
this computational-experimental approach will facilitate understanding how an alteration in a component of the
gland’s secretory machinery following γ-irradiation might alter saliva production. Ultimately, this approach is
designed to forecast potential novel therapeutic approaches for treating γ-irradiation induced salivary
dysfunction.

## Key facts

- **NIH application ID:** 10401792
- **Project number:** 5F31DE030670-02
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Amanda Michelle Wahl
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $47,552
- **Award type:** 5
- **Project period:** 2021-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401792

## Citation

> US National Institutes of Health, RePORTER application 10401792, Elucidating the Mechanisms of Salivary Gland Dysfunction Following Gamma-Irradiation Utilizing an Experimental and Computational Approach (5F31DE030670-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10401792. Licensed CC0.

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