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New grant to study how pediatric brain tumor, ependymoma, develops

Armed with new grant support, investigators at Nationwide Children's Hospital plan to examine how a common gene of the nervous system leads to the development of a devastating brain tumor, ependymoma. Robert A. Johnson, PhD, principal investigator in the Center for Childhood Cancer at The Research Institute at Nationwide Children's, has received a one-year $75,000 grant from the Matthew Larson Foundation for this research.

Ependymoma, an aggressive tumor that affects the central nervous system, is the first most common brain tumor in children. Ependymoma is chemo-resistant and is incurable in up to 40 percent of cases.

Previously, Dr. Johnson and colleagues at St. Jude Children's Research Hospital discovered that elevated levels of the Ephb2 gene cause embryonic neural stem cells to transform into one of the nine subgroups of ependymoma. The Ephb2 gene normally plays a critical role in cell development throughout the nervous system.

With the Matthew Larson Foundation grant, Dr. Johnson will be able to directly investigate just how the Ephb2 receptor is able to alter normal neural cells and cause ependymoma.

"Many studies have described Ephb2's ability to regulate cellular development in different cell types, but we don't yet know this receptor's role in transforming neural cells," said Dr. Johnson. "It seems that ependymoma develops when Ephb2 inhibits the ability of neural cells to differentiate and complete their cellular development."

During in vitro studies, Dr. Johnson plans to overexpress the Ephb2 receptor in neural stem cells to determine the receptor's role in these cells and to understand whether this overexpression halts cell progression. He also plans to examine the effects different types of mutations in the Ephb2 gene have on neural cell differentiation.

Future studies using a mouse model will help clarify these questions and also help determine if specific Ephb2 mutations can model another one of the nine ependymoma subgroups.

"I expect that our findings will shed light on the biology of these tumors and therefore allow us to develop more effective, targeted therapies," said Dr. Johnson.


Contact: Erin Pope
Nationwide Children's Hospital

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