A central focus of our lab is to uncover why regenerative ability declines as tissues mature. Using Drosophila wing discs as a model, we have shown that the loss of regenerative potential during late larval stages is not due to a failure of wound signaling, but rather due to targeted epigenetic silencing of damage-responsive enhancers. In younger tissues, injury activates a suite of damage-responsive, maturity-silenced (DRMS) enhancers that drive genes essential for regeneration. As development proceeds, Polycomb-mediated chromatin modifications progressively silence these enhancers, preventing re-expression of regenerative genes even though their developmental functions remain intact. This localized epigenetic repression at loci such as wg/Wnt6 and Mmp1 provides a molecular explanation for the age-dependent loss of regeneration.

Building on this discovery, we have used genome-wide chromatin-accessibility profiling to uncover dozens of additional DRMS enhancers and new regulators of regeneration, such as asperous (aspr), which directs the correct timing of repatterning and growth. Manipulating chromatin regulators, including the Polycomb group gene extra sex combs (esc), can partially restore enhancer accessibility and regenerative capacity in mature discs. By defining how developmental maturation restricts access to regenerative programs—and how to reverse this silencing—we aim to reveal strategies for reawakening latent regenerative potential in aging or injured tissues.