Reprogramming cells for repair of chronic wounds - regenerating soft tissue is critical for adequate healing after injury across many tissue types, but often does not occur due to inadequate…

The National Institute of General Medical Sciences awarded the Regents of the University of Michigan $409,941 on March 5, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to conduct research on reprogramming cells for repair of chronic wounds.

The research program centers on four investigative questions about how T-cell phenotypes contribute to inflammatory dysregulation in chronic wounds, whether T-cells can be reprogrammed to mitigate inflammation and resolve injury, how dynamic secretion of alarmin proteins impacts healing, and whether cellular responses to alarmins can be reprogrammed to respond with regenerative factors. The investigator will employ a synthetic biology approach to dissect the biology underlying chronic wound healing using two models: diabetic skin wounds and the foreign body response to implants. The work aims to develop responsive cell therapies targeting chronic wounds for regeneration and to address the unmet clinical need for healing chronic wounds where soft tissue regeneration currently fails due to inadequate microenvironmental cues and dysregulation of inflammatory processes.

Performance occurs at the University of Michigan in Ann Arbor, Michigan through December 31, 2030. The award is a Project Grant, the standard assistance type under NIGMS's basic research portfolio.

Reprogramming cells for repair of chronic wounds - regenerating soft tissue is critical for adequate healing after injury across many tissue types, but often does not occur due to inadequate microenvironmental cues. There remains an unmet clinical need to heal chronic wounds, and similar problems exist are ubiquitous across many wound types including: dysregulation of inflammatory processes and insufficient signal from regenerative factors. We propose a research program dedicated to deepening our understanding of chronic wounds and developing translational treatments that centers around four basic questions about reprogramming cellular responses in wound microenvironments: i) how do t-cell phenotypes contribute to inflammatory dysregulation?, II) can t-cells be reprogrammed to mitigate inflammation and resolve injury?, III) how does dynamic secretion of alarmin proteins impact healing?, and IV) can we reprogram cellular responses to alarmins to respond with regenerative factors. We know that multiple types of t cells are involved in healing wounds, but IT is not clear how they interact and directly influence healing or if reprogramming inflammatory t cells to regulatory ones could improve healing. Furthermore, we know that alarmins play a critical role in clearing pathogens and debris, but IT is suspected that overexpression of alarmins contributes to inflammatory dysregulation and non-healing. We hypothesize that a synthetic biology approach could enable more precisely dissecting this biology and yield responsive cell therapies that target chronic wounds for regeneration. Proposed herein we harness two models of chronic wound healing i) diabetic skin wounds and II) the foreign body response to implants, and we use these models to probe fundamentals of cellular responses to injury and develop improved regenerative therapies.