Beyond the code: revealing the core microRNA-mediated gene regulatory networks in human skin wound healing

Chronic wounds are common and severe diseases lacking effective treatment. To identify new therapeutic targets, a better understanding of the related molecular pathogenesis is a prerequisite. As an important layer of epigenetic control, microRNAs (miR) have been shown to regulate skin wound healing.

In the proposed project, we aim to identify the most robust miR regulators that control the gene regulatory networks (GRN) critical for human skin wound repair and to develop an innovative wound therapy based on the correction of the expression of these core miRs.

For this, we plan to (i) establish a high-resolution molecular map of human wounds with a focus on miRs-mediated GRNs (2021-2023), (ii) perform high-throughput functional screens for the miRs regulated during wound healing but dysregulated in chronic wounds (2022-2024), (iii) dissect the molecular mechanisms underlying the biological effects of the core miRs (2023-2025), and (iv) evaluate the therapeutic effect of the core miR/miR cocktail in clinically relevant wound models (2023-2025).

Findings from this project will fill in current knowledge gaps about how miR-regulated genetic networks instruct sophisticated biological phenotypes in human skin wound healing.

This study has the potential to set the stage for a paradigm shift in the strategy of searching for miR therapeutic targets, which may increase the success rate of clinical trials, thus making the development of novel miRNA-based therapy faster and cheaper.