Collaborative MBL Study Shows Regeneration and Cancer Might Share a Gene

Surrounded by tanks of bright-yellow sea anemones and growing salamanders, Uri Gat marvels at how these animals regenerate their bodies so well.

The Mexican “axolotl” salamander can regrow lost limbs, tail, parts of its retina, portions of the heart and even areas of the brain.

“If they can survive it, they can regrow it,” says Gat, a Whitman Fellow at MBL from the Hebrew University of Jerusalem.

Sea anemones, Gat’s area of expertise, take this to another level. If cut into several parts, each part regrows a perfect new animal within weeks.

Gat studies which genes play a role in whole-body regeneration and came to the MBL with a decade of experience working with the starlet sea anemone (Nematostella vectensis). Here, he collaborates with Karen Echeverri, a MBL associate scientist working on the regeneration programs of the axolotl (Ambystoma mexicanum) as well as of Nematostella.

Mexican “axolotl” salamander (Ambystoma mexicanum). Credit: Jane Marks

Gat is interested in the Cthrc1gene, which may play an important role in vertebrate regeneration. He was the first to identify Chrc1 to be un-regulated in a regeneration screen in Nematostella, an invertebrate, suggesting the gene has an ancient role in regenerative processes.

This same gene is found in humans too, but has been seen in a different light. When the gene is over-expressed in humans, it has been linked to cancer and seems to have a role in multiple types of tumor growth and invasion.

“If we understand what is happening with this gene in sea anemones, then we might be able to understand how it works in people and this may help in treatments of all those deadly cancers,” says Gat.

Uri Gat in his lab at MBL. Credit: Jane Marks

Gat began studying molecular biology in the late 1980s and was soon drawn to developmental biology. He was inspired by Thomas Hunt Morgan, one of the founders of the science of regeneration, who won a Nobel Prize in 1933 for discovering the role of chromosomes in heredity. (Morgan spent his summers at MBL studying early development and regeneration in marine organisms and his Nobel Prize is on display in the MBL WHOI Library).

Gat hopes his research, now focused on the role of Chrc1 in regeneration, will later reveal how the gene functions. During his Whitman fellowship, he and Echeverri explored Cthrc1’s expression in regenerating axolotls. They plan to eventually use CRISPR-Cas9 genome editing to “knock out” the gene during regeneration in the axolotl and see how it might alter the regenerative process.

While he goes back to Jerusalem at the end of this month, Gat hopes to return to MBL next summer, excited at the prospect of continued collaboration and discoveries with scientists like Echeverri at MBL.