a) Unraveling the Regulatory Mechanisms of cardiac Tissue Regeneration Enhancer Elements (TREEs).
The field of regenerative medicine has been primarily focused on identifying essential genes required for tissue regeneration. Yet, virtually nothing is known about the regulatory mechanisms controlling the expression of these genes. Previously, we identified the first Tissue Regeneration Enhancer Element (TREE), which can activate tissue regeneration programs. We reported a short DNA sequence, which is located upstream of leptin b (lepb), as a lepb-linked regeneration enhancer (LEN). This LEN does not show activity during development, but is robustly activated upon fin or cardiac injury. LEN activity is strongly maintained during fin or heart regeneration, but is completely decommissioned when regeneration is completed. My laboratory addresses how regeneration-specific TREE activity is controlled during tissue regeneration using LEN as a TREE representative. These studies will illuminate our understanding of gene regulatory networks underlying tissue regeneration and pave the way for future applications of improving tissue repair in mammals.
b) Identifying New Regulatory Factors Required for Tissue Regeneration.
Zebrafish is amenable to forward genetic screening, a powerful approach to discover novel factors affecting the phenotype. To identify novel regeneration factors, previously PI performed the forward genetic screening during postdoctoral training and isolated many mutant families which exhibit fin regeneration defects in a temperature-dependent manner. We continue to study these mutant families, and 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 heart. This work will reveal novel molecular mechanisms that are important for regeneration of adult tissues and will lead to new ideas and paradigm-shifting discoveries.
Our experiments will provide a fundamental insight into tissue regeneration, and they have an additional potential to inform approaches for comprehending and enhancing the limited regenerative capacity displayed by humans.