Wound repair and tissue regeneration; Drosophila genetics; Development and patterning

After wounding or injury some organisms, tissues and organs carry out an elegant process of regeneration to repair and replace the lost tissue. By studying model systems that regenerate well we can understand the mechanisms that promote regeneration and use them to manipulate healing and re-growth in critical human organs.

The process of regeneration involves a series of steps, each of which is poorly understood. Some outstanding questions are:

• How does a tissue sense damage?
• How does a damaged tissue initiate new growth?
• How is regenerative growth constrained so that it replaces only what was lost?
• How are cell fates properly specified within the new tissue?
• Does regeneration mimic development? If not, why?
• Are there regeneration-specific growth and patterning mechanisms that are required to replace the lost structure?

My lab aims to answer these questions using the regeneration of a simple epithelial tissue, the wing imaginal disc, in the model organism Drosophila melanogaster.

We use genetic tools to induce tissue damage and regeneration in the developing Drosophila wing. Using this method we can induce tissue damage and regeneration in hundreds of animals simultaneously, enabling high-throughput experiments, forward genetic screens, and genomic approaches to identify the genes and mechanisms that regulate each step in regeneration.

Current projects in the lab:

• Patterning and Development. We are characterizing expression of developmental patterning genes in regenerating tissue to determine the extent to which regeneration mimics development. When regeneration deviates from normal development, we are trying to understand how and why. We are also characterizing genes that are required for cell fate and pattern during regeneration but not during normal development (see Schuster and Smith-Bolton, Developmental Cell 2015).
• Chromatin. We are exploring how tissue damage induces the changes in gene expression that drive regeneration. We have focused on chromatin modifiers and remodeling complexes as key regulators of specific aspects of regeneration and subsets of regeneration genes.

In addition, the novel regeneration genes identified in our genetic screen and transcriptional profiling are leading us in exciting new directions. Stay tuned!