# Epigenetic predisposition and pathogenic mechanisms of recessive dystrophic epidermolysis bullosa

> **NIH NIH R21** · THOMAS JEFFERSON UNIVERSITY · 2022 · $205,920

## Abstract

Abstract
Fragility of the skin, development of poorly healing and chronic wounds, fibrosis, and squamous cell carcinoma
(SSC) are common features in patients suffering from hereditary Recessive Dystrophic Epidermolysis Bullosa
(RDEB). The disease is caused by mutations in Col7A1 gene, which lead to lack or dysfunction of type VII
collagen and poor anchorage of epidermis to dermis. Multiple investigations, including studies from our group,
addressed both RDEB pathophysiology and therapy, and defined factors contributing to RDEB moribund
symptoms. It remains unclear why some RDEB skin lesions heal, while other progress to non-healing wounds
in the same patient, or why patients harboring same molecular defect in Col7A1 gene may have drastically
different cutaneous manifestations. Here, we hypothesize that epigenetic changes occurring in RDEB
epidermis affect wound healing, fibrosis, and SCC development and that epigenetic changes could be
pharmacologically attenuated to facilitate restoration of RDEB skin integrity after injury and reduction of morbid
consequences. Our preliminary data showing drastically reduced H3 histone acetylation and highly significant
levels of 5-mC DNA methylation in the RDEB epidermis as well as methylation of promoters of specific genes
involved in fibrosis, cell cycle control, and cancer in the primary RDEB-derived keratinocytes strongly support
proposed hypothesis. Our exploratory project is designed to define the role of epigenetic regulation of gene
expression in RDEB epidermis, outline target genes, and define molecular mechanism(s) responsible for
epigenetic changes. In this project, we will also assess whether pharmacological intervention can be used to
lessen moribund factors and alleviate moribund RDEB symptoms. The Specific Aims of the project are: 1) To
investigate molecular mechanism of epigenetic control, epigenetic changes, and specific targets in RDEB
epidermis; and 2) To investigate the contribution of epigenetics to RDEB pathogenesis and evaluate the utility
of epigenetic inhibitors to reduce RDEB-associated cutaneous manifestations. It is anticipated that completion
of the current project will provide us with the crucial information regarding the role of epigenetic factors in
RDEB, and illuminate the path to better management of RDEB-associated painful and moribund manifestations
and define molecular pathways controlling epigenetic gene regulation as relevant to wound healing, fibrosis,
and SCC susceptibility.

## Key facts

- **NIH application ID:** 10453091
- **Project number:** 1R21AR079706-01A1
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **Principal Investigator:** OLGA IGOUCHEVA
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $205,920
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10453091

## Citation

> US National Institutes of Health, RePORTER application 10453091, Epigenetic predisposition and pathogenic mechanisms of recessive dystrophic epidermolysis bullosa (1R21AR079706-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10453091. Licensed CC0.

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