Research

Dissecting regeneration and large-scale tissue morphogenesis

Some vertebrate animals, such as teleost zebrafish and urodele amphibians, are able to regenerate complex tissues after major injuries. Understanding how and why natural regeneration occurs in these animals is the basis of my research program, as the answers may be applied to transform medicine as we know it. Currently, one of the key challenges in regenerative biology is to understand how individual cells within large populations are able to work together in a timely manner to fully restore complex tissues, with appropriate sizes, patterns, and functions. My research program combines large-scale cell imaging and genetics with systems-level analyses in order to discover new mechanisms and principles that dictate tissue-scale cell response during regeneration.

Since I started my laboratory at ICOB in July 2016, we have focused our efforts on three major knowledge gaps, which I expected would be best addressed using the zebrafish model. First, I want to know how the wound healing process is regulated upon amputation injuries. Although this process is essential to initiate regenerative response, little is known about the cell dynamics that enable rapid wound healing to occur in highly regenerative animals. I expect this research direction to identity new strategies for jumpstarting wound healing and/or regenerative responses in less-regenerative animals. Second, I want to identify pivotal genetic regulators of regeneration and dissect their working mechanisms. To realize this goal, we will use a collection of regeneration mutants that we recovered from a forward genetic screen. Third, I want to understand how large numbers of cells are coordinated in real-time as complex tissues are being built in living animals; I have a long-standing interest in developing multiplex cell tagging tools, live imaging platforms, and high-content quantitative analyses for capturing cell dynamism at multiple scales and in three-dimensional space.

Current projects in the lab

1. How do regenerative animals achieve rapid wound healing?

2. How do regenerative animals recall their missing parts during regeneration?

3. How do different cells behave in a population to enable post-embryonic growth and regeneration?