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Understanding the complications of wound healing in patients with Recessive Dystrophic Epidermolysis Bullosa

Grant Title: Exploring innate immunity in wound healing complications in RDEB patients

Investigator: Professor Dr. Sabine Eming

Co-investigators: Dr. Dimitra Kiritsi and Dr. Alexander Nystrom

Institution: University Hospital of Cologne, Germany

Start Date: Q2 2018                        End Date: Q1 2021                   Duration: 3 years

Grant amount: €194,500 (Co-funded by DEBRA Ireland)

Lay Summary

How does the body respond to wounds?

Cells of the immune system are an integral component of the body’s own or natural ability to restore tissue function after injury. After most types of tissue damage including blistering in EB patients, specific immune cells particularly monocytes and macrophages serve two key roles: to stop the damage and subsequently to help repair the tissue. Monocytes typically circulate in the blood for 1–3 days before migrating into tissues, where they become macrophages, there they eliminate harmful materials such as foreign substances, cellular debris and cancer cells.

The repair process requires macrophages to initially promote positive inflammation that aids cell defence, and then later when the immediate danger has passed to reduce inflammation to support resolution and repair. Previous research has shown that the tightly controlled dynamics between this pro-inflammatory and resolution response is fundamental for efficient healing.

What is the aim of this research?

This group plans to uncover the role of macrophages in wound healing in Recessive Dystrophic EB (RDEB) patients and to identify strategies to restore the function of these important cells in wounds of RDEB patients. Macrophages are also integrally linked to cancer formation and mechanistically they are likely placed at the interface between a poorly healing wound associated with RDEB and the potential for gradual transformation of the wound into cancer.

The aim of this project is to understand the fundamental mechanisms underpinning how immune cells assist and impair wound healing in RDEB patients to not only advance the development of new therapies that accelerate wound closure (e.g. wound dressings that may dampen chronic inflammation) but also to develop diagnostic tools to monitor when a poorly healing wound may become malignant or cancer forming.

This 3 year laboratory project will use samples from RDEB patients to establish the function of immune cells in the sequential stages of wound healing.

What is important about this research?

We believe that by increasing our understanding of how immune cells, in particular macrophages, function to facilitate the tissue repair response and to suppress scarring and carcinogenesis, that we will be able to improve the quality of life of individuals with RDEB.

Investigator Biography

Sabine Eming is Professor of Dermatology and Head of the interdisciplinary Wound Healing Centre at the University Hospital of Cologne, Germany. Her interests are in understanding the mechanisms how the skin in EB individuals senses tissue damage and how these events translate into a regenerative response or wound healing complications including excessive scarring and cancer. Her research aims to explore the function of the immune response that underlies the pathology of impaired wound healing in EB patients and to help identify strategies for pharmacological interventions to normalize would healing in this disease.