# Modulating the PI3K Pathway During the Managing of Wound Contracture and Accelerated Healing - Equipment Supplement

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $225,000

## Abstract

The skin is the largest organ in the body with remarkable physiological and social functions. The epidermal
portion of the skin is responsible for waterproofing the body and acting as a mechanical barrier; thus, it is
associated with vital functions. Upon injury, the immediate response of the epidermis and its stem cells aims at
the reestablishment of local homeostasis; however extensive injuries, often observed in burn patients, may
overwhelm the capacity to heal. If the epidermis-driven homeostasis is not restored, the organism undergoes
dehydration and increased chances for infection and death. New therapeutic strategies aiming at accelerated
epithelial migration and accumulation of epithelial stem cells are in great need to improve the health of burn
patients and the achievement of better clinical outcomes. Our research bridges new findings in the field of stem
cell biology with recent understanding of the role of the phosphatidylinositide 3-kinases (PI3K) molecular
mechanisms in response to epithelial injury. PTEN was initially identified as a negative regulator of the PI3K
signaling, the main regulator of cell growth, metabolism, and survival. By targeted disrupting the PTEN gene
from the epithelial layer of the skin containing stem cells, we observed a brisk activation of cellular proliferation
associated with increased migration. Moreover, we found that disruption of PTEN from the epidermis also
results in the accumulation of epithelial stem cells indicating a critical role of the PI3K signaling pathway in the
maintenance of epithelial homeostasis and response to external injuries. Here, we propose a novel therapeutic
strategy to treat wounds by increasing the population of skin stem cells at the donor site before the isolation
and graft in the injured recipient site. Furthermore, we will determine the therapeutic effectiveness of
pharmacological action on the PI3K signaling during the re-epithelization and scarring after burn. Human-
relevant preclinical animal models will be used to test our hypothesis on the efficacy of the PI3K in the
treatment of burn. This application is significant; once that will explore novel druggable pathways capable of
accelerating epithelial migration and wound closure, induce accumulation of epidermal stem cells, and reduce
the development of wound scar.

## Key facts

- **NIH application ID:** 10133769
- **Project number:** 3R01GM120056-04S1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Rogerio Moraes Castilho
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $225,000
- **Award type:** 3
- **Project period:** 2017-06-19 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133769

## Citation

> US National Institutes of Health, RePORTER application 10133769, Modulating the PI3K Pathway During the Managing of Wound Contracture and Accelerated Healing - Equipment Supplement (3R01GM120056-04S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10133769. Licensed CC0.

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