# Cellular Plasticity and Regeneration after Radiation Damage in Drosophila

> **NIH NIH R35** · UNIVERSITY OF COLORADO · 2021 · $26,127

## Abstract

RESEARCH EXPERIENCE PLAN
Summary of the parent R35
 More than half of cancer patients receive ionizing radiation (IR), alone or as a component of their
treatment (www.cancer.org). IR induces DNA damage to kill cells. Surviving cancer cells could, however,
regenerate the tumor, leading to treatment failure. While we understand much about how cells repair DNA
damage or undergo cell death, how tumors regenerate remains an active area of research with key
questions remaining unanswered.
 Our overall objective is to understand how tissues regenerate after damage by IR in vivo in a
multicellular context, to identify and characterize the genes involved in this process, and to develop genetic
and chemical tools to manipulate the function of these genes.
 We have been using Drosophila melanogaster to study regeneration after IR damage because we
can perform large-scale gene discovery and molecular genetic analysis, and use precision lineage-tracing
to follow specific subsets of regenerative cells over time as they interact with their surroundings. DNA
repair, cell death and regeneration in Drosophila share genetic and molecular features with vertebrates.
Chemical modulators of IR-induced regeneration we discovered in Drosophila behave similarly in human
cancer models. These findings provide proof of concept that what we learn in Drosophila will likely apply to
humans.
 Regeneration of Drosophila larval organs called imaginal discs occurs without a dedicated stem cell
pool. We recently identified a previously unknown mode of regeneration in Drosophila larval wing discs,
whereby epithelial cells acquire stem cell-like properties. These properties include the ability to change cell
fate and translocate to areas of the disc with greater need for cell replenishment. The ability to behave like
stem cells, we found, is induced by ionizing radiation (IR) and is limited to specific subsets of cells within the
wing disc. IR-induced stem-ness in Drosophila parallels the increasingly appreciated ability of cancer
treatments including IR to induce stem cell-like properties in non-stem cancer cells. This project will address
the following essential questions. What are the consequences of IR that induce stem cell-like behavior in
non-stem cells? Why do some irradiated cells respond by displaying stem cell-like behavior while others do
not? What internal and external factors regulate the induction of stem cell-like behavior? Answers to these
questions will not only increase our understanding of regeneration after IR damage but also will identify
mechanisms that may be modulated to improve treatment outcome in human cancers.

## Key facts

- **NIH application ID:** 10434311
- **Project number:** 3R35GM130374-03S1
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** Tin Tin Su
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $26,127
- **Award type:** 3
- **Project period:** 2019-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10434311

## Citation

> US National Institutes of Health, RePORTER application 10434311, Cellular Plasticity and Regeneration after Radiation Damage in Drosophila (3R35GM130374-03S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10434311. Licensed CC0.

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