# Cellular and Molecular Mechanisms of Regenerative Growth and Repatterning

> **NIH NIH R35** · UNIVERSITY OF VIRGINIA · 2024 · $397,492

## Abstract

Project Abstract
Regenerative abilities vary significantly both between different species and between distinct tissues of a
given species. Despite recent advances, many fundamental questions persist regarding the cellular and
molecular mechanisms that govern effective tissue regeneration. This research program strives to
uncover the genes and gene regulatory networks (GRNs) that operate within individual cells during
distinct phases of regeneration. For regeneration to occur, surviving cells need to launch a response that
promotes localized cellular reprogramming, proliferation, and tissue repatterning to replace what was
lost. This investigation will shed light on how tissue regeneration is orchestrated by determining the genes
and GRNs that trigger a regenerative response, support regenerative growth, and ultimately reestablish
proper cell fates in the newly generated tissue. The work focuses on tissue regeneration in the powerful
genetic model organism Drosophila melanogaster in combination with state-of-the-art single-cell
technologies. Many crucial processes during regeneration occur in small subpopulations of cells, the
study of which has been revolutionized by single-cell technologies. Investigating regeneration in
Drosophila provides many key advantages including the availability of powerful genetic tools that support
dissection of gene function in vivo, large-scale screens for genetic interactions, and quantitative
assessments of regenerative growth, and repatterning. The goals in the coming years are to: (i)
investigate blastema formation and the establishment of the regenerative microenvironment. What are
the cellular and molecular events that activate, sustain, and organize cell-cell coordination during the
early phase of regeneration? (ii) elucidate the genes and GRNs that drive the distinct phases of
regeneration by unraveling gene regulatory mechanisms of the transcriptional programs activated during
the key phases of regeneration: blastema formation, regenerative growth, and regenerative repatterning;
(iii) compare tumorigenesis versus regeneration to uncover critical regulatory mechanisms. Tumors have
been shown to co-opt pro-regenerative GRNs to drive tumor growth. Therefore, we aim to discover the
regulatory mechanisms that effectively terminate regenerative growth by contrasting tissues undergoing
regeneration versus tumorigenesis. Together these areas of research will advance our understanding of
cell-type specific gene regulatory networks that initiate blastema formation, promote effective
regenerative growth, and regulate cellular repatterning during regeneration. These insights will address
central questions in the fields of developmental and regenerative biology and ultimately contribute to the
pioneering field of regenerative medicine.

## Key facts

- **NIH application ID:** 10940657
- **Project number:** 1R35GM155091-01
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Melanie I. Worley
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $397,492
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10940657

## Citation

> US National Institutes of Health, RePORTER application 10940657, Cellular and Molecular Mechanisms of Regenerative Growth and Repatterning (1R35GM155091-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10940657. Licensed CC0.

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