Unlocking new pathways in regenerative medicine
A fluorescent microscopy figure. Photo courtesy of Rob Harris
In the quest to advance regenerative medicine, the Harris Lab at Arizona State University is making groundbreaking strides. Focused on tissue regeneration and the intricate biology of cell death, the lab has uncovered a novel phenomenon with far-reaching implications for improving wound healing and injury repair.
This research not only fills a critical gap in our understanding of necrotic damage but also holds promise for developing innovative therapies for a wide range of medical conditions.
Led by Rob Harris, assistant professor in ASU's School of Life Sciences, the Harris Lab investigates how cells respond to necrotic damage — a poorly understood form of cell death caused by traumatic injuries, infections and common diseases such as heart attacks, strokes and diabetes. Necrosis, unlike the more controlled process of programmed cell death (apoptosis), often results in widespread tissue damage and inflammation. Understanding how tissues repair themselves in the aftermath of necrosis could transform treatment approaches for these conditions.
The Harris Lab employs the larvae of the common fruit fly (Drosophila melanogaster) as a model organism. While small and seemingly simple, fruit flies possess a surprising ability to regenerate damaged organs after various types of injuries, including physical trauma, irradiation and genetic disruptions. By leveraging this regenerative capacity, the lab is uncovering fundamental biological principles that could one day inform human therapies.
In their pivotal 2021 study published in Genetics, the Harris Lab identified an unexpected role for caspase proteins in tissue regeneration. Caspases are typically known for their involvement in apoptosis, wherein they help dismantle old or unwanted cells in a controlled manner. However, the lab’s research revealed something unexpected: Caspases activated by necrotic damage stimulate neighboring healthy cells to proliferate and contribute to tissue repair.
What’s even more remarkable is that this regenerative response occurs at a distance from the site of necrosis, suggesting the existence of long-range signaling mechanisms. These signals appear to mobilize surrounding healthy tissue to participate in the repair process, providing a more comprehensive response to injury.
“This finding is significant because it not only adds to the body of evidence that caspases are involved in signaling events that promote repair, but also shows for the first time that this phenomenon occurs following necrosis, one of the least understood and most prevalent forms of tissue damage in people,” Harris says.
This discovery not only challenges existing paradigms about the role of caspases but also expands our understanding of how tissues can coordinate their regeneration efforts after severe damage.
Building on these findings, the lab published a follow-up study in eLife last month. This research delves deeper into the molecular pathways underlying the observed phenomenon, providing new insights into how tissues achieve regenerative competence. By mapping the signaling events that link necrotic damage to caspase activation and subsequent cell proliferation, the lab has created a foundation for further exploration of these processes.
The significance of this work has not gone unnoticed. Andreas Bergmann, a renowned expert in cell death and tissue regeneration at UMass Chan Medical School, authored an eLife Insight article highlighting the groundbreaking nature of the Harris Lab’s discoveries. In his article, Bergmann notes, “By understanding the factors that confer regenerative competence to specific regions of the tissue, new fundamental principles of tissue regeneration may be uncovered. These insights could potentially be leveraged to develop novel therapeutic approaches for enhancing regenerative capacity in human tissues affected by necrotic damage.”
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