# Understanding Skin Tissue Repair in Live Mammals

> **NIH NIH R01** · YALE UNIVERSITY · 2021 · $557,795

## Abstract

SUMMARY
 Skin protects our body against the outer environment, and its ability to repair upon injury is directly
connected to both disease and survival. Failure to properly repair injured tissue can result in severe damage,
such as the formation of chronic wounds, which are associated with severe complications and even death.
Approximately 6.5 million people in the US suffer from chronic non-healing skin wounds, such as diabetic
ulcers. At least
US$25 billion is spent annually to treat chronic wounds, and this cost is skyrocketing due to
increasing health care costs, an aging population and the growing rates of diabetes, cancer and obesity. Thus,
chronic wounds represent a substantial burden on public health and the health care system.
 We still lack fundamental knowledge of distinct cellular behaviors that are coordinated to achieve tissue
regeneration and repair. The goal of this proposal is to unravel how cell behaviors are properly orchestrated on
the single-cell and tissue-scale level during repair. The critical barrier to addressing these fundamental
questions lies in the inability to study these dynamic processes in an intact mammal. Further, interrogating skin
repair is complicated by the coexistence epithelial stem cells intermixed with resident immune cells, both of
which are implicated in the repair process. To this end, my laboratory has established an in vivo strategy to
directly visualize and manipulate epithelial cells and immune cells in the skin epithelium of live mice, taking
advantage of its unique accessibility, continuous regeneration throughout its lifetime, and efficient repair.
 We utilize a novel, non-invasive two-photon imaging approach to follow epithelial and immune cells
during the repair process. We combine intravital microscopy with methods that we developed to manipulate
distinct epithelial cell repair behaviors or resident cell types in vivo. This integrated approach allows us to
dissect the coordination and functional significance of distinct cell activities, populations and interactions during
repair. Thus, we have begun to understand the complex interplay between distinct epithelial cell behaviors, and
between distinct cell types within the epidermis, that contribute to wound closure.
 The goal of this proposal is to advance our understanding of how cell populations and behaviors are
orchestrated to achieve wound repair in skin, by using an integrated approach of cutting edge imaging
technology, genetic manipulation and cell biology. Given that many aspects of wound repair are widely
conserved in other organs, our findings will be relevant to other tissues as well, and will provide an important
foundation to improve wound repair in a variety of patients.

## Key facts

- **NIH application ID:** 10091970
- **Project number:** 5R01AR072668-04
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Valentina Greco
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $557,795
- **Award type:** 5
- **Project period:** 2018-03-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10091970

## Citation

> US National Institutes of Health, RePORTER application 10091970, Understanding Skin Tissue Repair in Live Mammals (5R01AR072668-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10091970. Licensed CC0.

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