1. Heart regeneration
Most human genes are highly conserved in zebrafish. However, unlike adult humans, zebrafish can regenerate their damaged heart tissues. This discrepancy in heart regeneration is attributable to differential expression of essential genes upon cardiac injury. Major efforts have been made to generate the molecular blueprint of heart regeneration, yet regulatory events are poorly understood. Previously, we reported the first Tissue Regeneration Enhancer Elements (TREEs), short DNA sequences which can activate tissue regeneration programs. The activity of TREE is very specific: restricted to wound tissues and only during regeneration. Intriguingly, the specificity of TREE can be engineered with regenerative factor, and we showed that TREE-engineered pro- or anti-regenerative factors do not influence development but are strongly induced upon injury, suggesting that enhancer engineering with TREE can modulate tissue regeneration positively or negatively. Our laboratory will employ various methodologies including transgenic assays, small molecule screening, and biochemical analysis to uncover how cardiac TREE activity is precisely controlled. Investigation of cardiac TREE will allow us to solve the mystery of heart regeneration and further to inspire the therapeutic strategy to unlock our bodies’ latent healing power to give back healthy cardiac tissues to patients.
2. Fin regeneration
Zebrafish is amenable to forward genetic screening, a powerful approach to discover novel factors affecting the phenotype. To identify novel regeneration factors, during my postdoctoral training I carried out forward genetic screening and isolated many mutant families which exhibit fin regeneration defects in a temperature-dependent manner. We continue to study these mutant families here at UW-Madison. The goal of this project is to identify novel genes and their cellular and molecular mechanisms in fin regeneration and further to determine their roles in regeneration of other tissues including heart. This work will discover novel findings that are important for tissue regeneration.