Assistant Professor of Biochemistry, University of Washington
Abstract: Humans have a limited capacity to regenerate complex differentiated tissues. In contrast, many amphibians are readily able to regenerate muscle, spinal cords, eyes and even entire limbs. Among amphibians, frogs such as Xenopus tropicalis occupy a uniquely powerful position as a regenerative system, because they can regenerate all of these tissues well as tadpoles, but lose this competence as they undergo metamorphosis. Our goal is to identify the molecular mechanisms that enable differentiated tissues to regenerate in tadpoles but are restricted in adults. In pursuit of this goal, our particular interest is in understanding the gene regulatory landscape that underlies transcriptional activation of new gene products during regeneration. While many individual genes have been implicated in specific regenerative processes, a comprehensive understanding of how the transcriptome and chromatin environment are remodeled during regeneration has been lacking. We have taken an integrated genomic approach during X. tropicalis tail regeneration to understand the dynamic changes that occur in gene expression and the underlying chromatin landscape. Using this combined approach, our research has uncovered new categories of gene expression that are prioritized early in regeneration, as well as evidence that chromatin is rapidly remodeled throughout the nucleus in response to amputation. These discoveries provide new insights into the molecular mechanisms that govern regenerative responses in complex vertebrate tissues.