# Cell fusion and the role of syncytia in the response to epithelial damage

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2022 · $332,198

## Abstract

Project Summary
Led by a multi-PI team of a cell biologist and a biophysicist, this project is a renewal of our
investigation into the cellular detection of and responses to wounds. For our model system, we
use the Drosophila pupal notum, a diploid epithelial monolayer, and we wound it by laser
ablation. Although the tissue is diploid, the region at and near the wound margin is dominated
by giant syncytial cells. The origin, function, and fate of these syncytial cells are all unknown.
Using live imaging, we have found that the giant syncytia are formed via cell-cell fusion of
multiple diploid cells. These fusions occur within ~20 minutes of wounding and the resulting
syncytial cells migrate more quickly and close wounds faster than diploid cells. By the end of
tissue repair, most of these giant syncytia are eliminated from the epithelium. Interestingly, we
have found that the amount of cell fusion and syncytia formation depends on the mode of
wounding. We will compare wound healing behaviors in wounds that lack syncytia and those
that have syncytia to investigate how these giant cells increase the rate of wound closure (Aim
1). In Aim 2, we will investigate how wounds induce mononuclear diploid cells to fuse into
syncytia. In Aim 3, we will analyze the long-term fate of these syncytia, which appear to die by
apoptosis and extrusion as wound closure is ending. Syncytial and polyploid cells have been
observed in other organisms and tissues in response to wounds, but our system is the first to
make a detailed analysis of their formation, contribution, and elimination possible using live
imaging.
Cells involved in wound-healing generally share behaviors with tumor cells, and the wound-
induced giant syncytial cells may represent the wound equivalent of Giant Polyploid Cancer
Cells, a syncytial cell type found in many cancers. Giant Polyploid Cancer Cells are malignant,
resistant to all therapies, and appear to be a major source of tumor cells fueling metastasis and
relapse. We expect that our studies into the adaptive functions of wound-induced syncytia will
be important for understanding the biology, origin, and potential therapies for maladaptive Giant
Polyploid Cancer Cells.

## Key facts

- **NIH application ID:** 10520332
- **Project number:** 2R01GM130130-05
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** M. Shane Hutson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $332,198
- **Award type:** 2
- **Project period:** 2018-08-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10520332

## Citation

> US National Institutes of Health, RePORTER application 10520332, Cell fusion and the role of syncytia in the response to epithelial damage (2R01GM130130-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10520332. Licensed CC0.

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