My laboratory studies the molecular and cellular mechanisms underlying tissue regeneration.  To examine this long-standing biological problem we investigate regeneration in freshwater planarians.  Planarians can completely regenerate entire worms from small body fragments.  Their amazing capacity for regeneration is supported by a population of adult pluripotent stem cells (called neoblasts), which serve to replace cells lost during normal cell turnover and after wounding. Our work focuses on two broad areas:

I. The molecular basis underlying neurogenesis during regeneration and tissue renewal. One of the truly amazing properties of planarians is their ability to repair the CNS, a capacity that is limited in most animal models currently studied. In addition, depending on their metabolic needs, planarians display great plasticity by altering the number of cells (including neurons) during periods of growth and de-growth. Planarians are amongst the simplest organisms to possess bilateral symmetry and a CNS; the CNS consists of bi-lobed cephalic ganglia (brain) that are connected to two longitudinal ventral nerve cords projecting posteriorly along the length of the animal. Distinct nerve cell types have been described by histochemistry and molecular markers, which have been used to show that the cephalic ganglia are highly regionalized. Thus planarians provide an outstanding opportunity to investigate fundamental mechanisms underlying stem cell-based regeneration and re-modeling of the CNS.

II. Functional analysis of ubiquitin-mediated pathways controlling stem cell fate and tissue regenerationE3 ubiquitin ligases are a large and diverse family of enzymes responsible for transferring ubiquitin to specific proteins. Ubiquitylation regulates a broad range of cellular functions including DNA repair, transcription, trafficking, and regulated protein degradation. Ubiquitin-mediated proteolysis has been implicated in controlling the availability of transcriptional regulators required for cell differentiation and regenerative processes in widely divergent organisms, however, the function of ubiquitin ligases in tissue regeneration has not been systematically analyzed. Our goal is to identify genes encoding ubiquitin ligases in planarians and analyze their function in tissue renewal; the ability to inhibit ubiquitin ligase genes using RNAi will be combined with technologies designed to identify proteins modified with ubiquitin. This work will contribute to the broad goal of understanding the biological roles of ubiquitin ligases and identifying cellular targets required for stem cell regulation, tissue regeneration or body patterning.

This work is supported by a grant from the National Science Foundation: IOS-1350302.

Ubiquitylation involves sequential activity of three enzymes: E1 activating enzymes bind ubiquitin (Ub) via a thioester bond (-S-) in a process that requires ATP. Ubiquitin is transferred to an E2 conjugating enzyme. E3 ubiquitin ligases transfer ubiquitin to the substrate.

© Ricardo Zayas 2014