Charles Eberhart, M.D., Ph.D.
2010-2011 funding
Diffuse intrinsic pontine gliomas (DIPG) are among the most deadly pediatric brain cancers, with no effective therapies. Unfortunately, few models for these exist, severely limiting our ability to test new treatments for the patients who need them most. The goal of our research proposal is to develop accurate models of DIPG for pre-clinical therapeutic testing by introducing genetic alterations into normal human stem cells derived from the developing brain stem. Because key genetic alterations found in DIPG will be used, and our unique culture system contains the stem cell types from which DIPG arise, we believe that we will be able to create accurate models for these tumors. The specific genes whose roles will be examined include p53, c-Myc, hTERT, c-KIT, BMP4, and PTEN.
Our research team includes a neuropathologist (Dr. Charles Eberhart) and a pediatric oncologist (Dr. Eric Raabe), providing expertise in both the clinical and pathological aspects of the project. We will test the tumor forming capabilities of our model in cell culture, and also in animals by injecting the cells into the brains of special mice with limited immune response. We believe that our proposal will allow for progress to be made in treating patients with DIPG, because we can use these cell lines to screen for new drugs, test drug combinations, and look for factors conferring resistance to chemotherapy.
Thank you to Spring Aucoin and Jarrod Aucoin, Ali Rose Aucoin’s parents, for their support for DIPG. For this grant and a special project.
Hopefully, this will allow us to find molecular factors that represent an “Achilles’ heel” for pediatric high-grade gliomas of the brainstem.