Genomics, Biomarkers and Mechanisms of Healing in Chronic Wounds

Chronic wound is a major public healthcare burden that costs approximately $25 billion per year and affects about 1% of the US population. In healthy individuals, wound healing follows a set of orderly phases initiated with inflammation, followed by cell proliferation and finally extracellular matrix remodeling. On the contrary, chronic wounds are retained at a prolonged and perpetual inflammatory status and are not able to proceed to the subsequent healing phase. Chronic wounds are frequently found in individuals with diabetes, circulatory disorders, pressure ischemia, or infections. Our long-term goal is to characterize microbial roles in the delayed wound healing process towards more effective clinical strategies to improve the outcome of chronic wounds.

Chronic wounds demonstrate a delayed healing process and a reduced healing rate. In normal wounds, once the wound enters the healing phase the wound surface area shrinks at a consistent rate of 10% per week. Non-healing recalcitrant chronic wound are wounds with a reduced healing rate such that the wound surface area is reduced by no more than 40% after four weeks, and vice versa for healing wounds. We have carried out a pilot study in collaboration with Georgetown University to compare recalcitrant versus healing wounds focusing on the microbiome of the wound bed using 16S rDNA population surveys. Our preliminary data has demonstrated that wound biofilm collections from chronic wound specimens can yield adequate samples to study microbial diversity and profiles.

A newly funded NIH project entitled "Genomics, Biomarkers and Mechanisms of Healing in Chronic Wounds" has been awarded to Georgetown University to conduct a study with a cohort of ~200 patients with recalcitrant or healing wounds in collaboration with JCVI.  Samples will be selected from patients enrolled in the Georgetown University Wound Etiology and Healing biospecimen and data repository (WE-HEAL). Wound microbiome analysis using microbial profiling and RNA-seq will be carried out at JCVI.  To characterize the wound microbiome in recalcitrant versus healing wounds, we will use 16S rDNA population surveys to study microbial diversity and relative abundance in the wound biofilm. We will also use whole genome expression profiling via RNA-seq to identify virulence and pathogenicity markers from expressed genes and pathways with associative roles in delayed wound healing. Multivariate analysis will be performed to correlate the wound microbiome and virulence markers with the wound outcome.

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