# Complexity and the Wound Healing Response

> **NIH NIH R35** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2022 · $394,253

## Abstract

Project Summary
The ability to heal is essential for human health. The remarkable wound healing capacity of humans (and
indeed of all animals) is a complicated process. Genomic studies suggest that more than 5000 mRNA
transcripts change expression patterns during wound healing, and more than a dozen cell types participate.
Despite the large number of cells and molecules that are involved, many aspects of the complexity of wound
healing are not well understood. Systems approaches have established the breadth of genes involved in
healing, and have compared gene profiles in different types of wounds. Yet many questions about the
networks and interactions within wounds are still unanswered. The research proposed here couples novel
quantitative approaches with basic biologic research to examine several questions related to the complexity
and diversity of the events that compose tissue repair. The research plan addresses three separate but
complementary questions. Question 1 asks - What are the regulatory pathways that underlie the differential,
site specific healing that is seen in skin versus oral mucosa? Studies by us and others have shown that
wounds in the oral mucosa exhibit faster re-epithelialization, reduced inflammation, a better-developed
angiogenic response, and less scar formation as compared to skin. Oral mucosal and skin wounds also have
distinctive transcriptomes. The central concept underlying Question 1 is that key transcription factors are
responsible for the differential healing seen in these two tissues. The research approach uses state-of-the-art
algorithms and in vivo experiments to discover and validate the transcription factors (and their networks) that
distinguish oral mucosal and skin healing. Question 2 asks - What is the level of redundancy in healing
wounds? This question explores the robustness of healing by assessing molecular redundancy. Redundancy
has been posited to exist in wounds as a “fail-safe” mechanism, insuring that wound healing proceeds even if
some key elements are functionally inactivated. The underlying concept for Question 2 is that significant gene
compensation occurs in wounds when specific genes are deleted. The approach uses genetically deficient
(“knockout”) mice to examine the extent of redundancy in healing wounds. Question 3 asks- Can quantitative
models be used to predict wound healing outcomes? Our ongoing collaboration utilizes a novel computational
modeling framework called the dynamic cellular finite-element model (DyCelFEM) to develop a model of
epithelial repair that is predictive of healing responses. The research plan extends the model to include
additional features of wound healing, such as angiogenesis. When completed, the model can be used to test
the effect of perturbations of single or multiple factors on healing outcomes. This advanced model will be a
powerful tool that can contribute to our understanding of both the pathophysiology of chronic wounds and the
development of therapeut...

## Key facts

- **NIH application ID:** 10322976
- **Project number:** 5R35GM139603-02
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** LUISA A DIPIETRO
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $394,253
- **Award type:** 5
- **Project period:** 2021-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10322976

## Citation

> US National Institutes of Health, RePORTER application 10322976, Complexity and the Wound Healing Response (5R35GM139603-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10322976. Licensed CC0.

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