# Cellular plasticity in salivary gland regeneration.

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2021 · $451,425

## Abstract

ABSTRACT
Radiation therapy, the predominant treatment for head and neck cancers, causes irreversible damage to
the salivary glands, due to the loss of secretory acinar cells. Recent data from our laboratory
demonstrates that human and murine salivary glands initiate acinar cell regeneration after radiation
treatment, but in contrast to injury by duct ligation, the salivary glands do not fully recover function.
However, the regenerative potential exhibited in irradiated glands implies that therapeutic strategies may
be developed to stimulate repair of radiation-induced damage. Emerging evidence suggests that cell
plasticity, defined as the ability of differentiated cells to re-enter the cell cycle, is a means of supplying
precursors for tissue regeneration. Evidence of cell plasticity has only recently been reported in salivary
glands. In studies of glands injured by duct ligation or ionizing radiation, we have identified three specific
cell populations that display plasticity. These include surviving regenerative cells that can repopulate
duct-ligated glands, a heterogeneous population of cells co-expressing duct and acinar cell markers with
unknown fate, and duct cells that can undergo lineage conversion to generate secretory acinar cells in
irradiated glands. Cellular plasticity, and the ability to convert cells from another lineage in vivo, offer
considerable potential for replacement of lost acinar cells. However, our knowledge of the mechanisms
that induce, regulate, and constrain this process is limited. We propose to compare different injury
models, for the response of salivary gland cells, and to define the conditions that induce plasticity.
Lineage tracing, which heritably labels cells and their descendants, will be used to investigate how cells
exhibiting plasticity contribute to regeneration, and the requirements for those cells to undergo lineage
conversion. Single cell RNA sequencing will be used to characterize the cell types involved in
regeneration, and gain insight into participating molecular pathways. The feasibility of stimulating
regeneration of endogenous cells through the introduction of exogenous factors will be explored. These
studies will determine how cellular plasticity and lineage conversion are involved in the response to injury
and regeneration of the salivary glands. Identification of the cells involved and the conditions driving
these processes may yield critical information for development of regenerative approaches to treat
xerostomia.

## Key facts

- **NIH application ID:** 10209154
- **Project number:** 1R01DE030626-01
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Catherine E Ovitt
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $451,425
- **Award type:** 1
- **Project period:** 2021-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10209154

## Citation

> US National Institutes of Health, RePORTER application 10209154, Cellular plasticity in salivary gland regeneration. (1R01DE030626-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10209154. Licensed CC0.

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