Discovering therapeutic targets in human iPSC-derived models of ZFTA::RELA ependymoma
Children with the brain tumor Supratentorial Ependymoma ("ST-EPN") have low survival rates (50% at 10 years) and very high relapse rates (70%). The only effective treatments for ST-EPN are surgery and radiation; sadly, there is no chemotherapy that is known to be effective in this disease. There is a big need for new treatments for ST-EPN, and a need for research to figure out those treatments. Researchers recently discovered that most cases of ST-EPN are caused by a "fusion oncoprotein" called ZRFus, and very little is known about how ZRFus works. I have now developed a new tumor model where the ZRFus has a "tag" on it that allows researchers to identify everything that ZRFus touches in the tumor cell: every protein, every gene that ZRFus targets to cause ST-EPN. To make this model, I start from "induced pluripotent stem cells" (iPSCs, which originally were made from the skin cells of adult humans). In the lab, I grow iPSCs to become brain stem cells, then I add ZRFus, and then I surgically implant those cells-with-ZRFus into the brains of mice. It takes about 3 months, but those implanted cells grow into brain tumors that strongly resemble ST-EPN. Examining the tumors, I can find the ZRFus by its "tag", and find everything that ZRFus is interacting with. Those interactors might be a part of ZRFus's tumor-causing toolkit, and are candidates for future therapeutic targets in clinical trials
Project Goals
The overall goal of my research is to improve cure rates for a deadly childhood brain tumor known as Supratentorial Ependymoma (ST-EPN). I have developed a new experimental model of this cancer, which I am using to discover the ways that it forms and grows, The short term goal is to figure out whether ST-EPN has an "achilles heel" vulnerability. The result of my experiments will be the identification of targets for testing in upcoming clinical trials, toward the goal of better outcomes for children with ST-EPN.

