Longitudinal Analysis of Disease Site Activities Impairing Wound Healing in Epidermolysis Bullosa and Development of Therapeutic Strategies
Abstract
Hereditary Epidermolysis Bullosa (EB) is a mechanobullous disease characterized by the fragility of the skin. Separation of skin layers, a hallmark of the disease, leads to the development of skin lesions ranging from skin blisters to chronic ulcerated wounds, which represent the major health-related burden for EB patients as these lesions are associated with infection,sepsis, dehydration, deformities, and cancer. Our previous findings along with several clinical observations strongly suggest that detailed characterization of molecular and cellular events impairing wound healing is crucial to improve stem cell-based and combination treatment modalities. The mechanisms that control the fate of the EB wounds remain poorly understood. Our overarching hypothesis is that an altered secretome along with microbial infection at EB wounds lead to the establishment of pro-inflammatory feedback loops and inhibition of wound healing and that targeting of chronic skin lesions with pharmacological treatments can restore aberrant wound healing and skin integrity. These questions were tested by investigating molecular and cellular mechanisms underlying unresolved wound healing, characterizing microbial dynamics and immunogenicity of the wound colonizing bacteria, and developing pharmacological approaches for EB treatment and management. By using samples from three major EB types, we identified type-specific changes in wound healing. We also delineated cellular populations and pathways preventing wound healing that were amenable for therapy development. In conjunction with state-of-the-art microbiome sampling and bio-informatics, our studies accelerated understanding of the differences between chronic and healing wounds. Conducted analysis of wound progression helped to define precipitating factors that predefine EB wound aberrations.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2022
- Accession Number
- AD1212326
Entities
People
- Olga Igoucheva
Organizations
- Thomas Jefferson University