Deciphering the balance between regeneration and tumorigenesis

Cancer incidence varies dramatically across species. The identification of endogenous mechanisms of tumor resistance promises to unveil novel strategies to combat tumors. The study of non-mammalian mechanisms of tumor control and resistance has long been hindered due to intractability of model systems. Novel tools and techniques have now overcome this barrier and made molecular phenotyping and loss-of-function assays feasible. This allows for examination of evolutionary-derived cancer resistance mechanisms. Some highly regenerative species, like salamanders, have been identified as cancer resistant but the mechanisms that impart this resistance are unknown. The major focus of study on these animals has been on regeneration, which indicate that regenerating tissue has a tumor-like gene signature. Though similar in gene expression and biological processes, the divergence of regeneration to tumorigenesis is not just rare, but actually strongly inhibited. In this project, we will take a genetic loss-of-function approach to investigate the limits and origins of tumor resistance in salamanders.