# Epigenetic Regulation of Skin Regeneration

> **NIH NIH P01** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $592,034

## Abstract

SUMMARY
Defective wound healing accounts for enormous morbidity and fiscal burden worldwide. Chronological aging of
skin is at the foundation of defective wound healing, although little is known regarding the underlying cause of
this association. However compelling data indicates that skin stem cells that become deficient as we age are the
basis for defective wound healing. Moreover, reversible epigenetic regulation plays a critical role in stem cell
health and maintenance. We therefore posit that the fundamental underpinnings of regenerative healing of skin
reside in the epigenetic regulation of skin stem cells. Here, we propose to study epigenetic changes in skin
regeneration in wound healing and aging, and test a newly discovered form of in vivo epigenetic
reprogramming that we predict will reverse the age and restore function to aging stem cells. Thus, the
primary goal of this project is to elucidate epigenetic mechanisms of skin stem cell regulation with focus
on DNA methylation/hydroxymethylation and histone modification, and to develop novel and practical
translational approaches to reprogramming age-related stem cell epigenetic aberrances. We have
assembled a synergistic interdisciplinary team of investigators with a history of pioneering discovery in the areas
of aging biology, epigenetics, epigenetic reprogramming, skin stem cell biology, dermatopathology and
biomarker application. We also have developed experimental models that encompass biodegradable wound
healing scaffold development, human skin xenotransplantation, three-dimensional bioprinting, and a mouse
model of epigenetically inducible premature aging. Thus, we will leverage multiple points of synergy, experience,
and collaborative interaction to tackle the complex and clinically important questions of age-related wound healing
deficiency. Most importantly, we will define and test the therapeutic effects of epigenetic reprogramming in our
novel and complementary pre-clinical model systems. This proposal presents a new approach of epigenetic
reprogramming of functionally deficient aging stem cells to enhance skin regeneration in order to heal chronic
wounds in the aging populace. If successful, such an approach could transform the way we think about the aging
process and treating age-related skin disorders.

## Key facts

- **NIH application ID:** 10494659
- **Project number:** 1P01AG071463-01A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Christine Guo Lian
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $592,034
- **Award type:** 1
- **Project period:** 2022-09-30 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10494659

## Citation

> US National Institutes of Health, RePORTER application 10494659, Epigenetic Regulation of Skin Regeneration (1P01AG071463-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10494659. Licensed CC0.

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