Funded Grants

Grantee: MD Anderson Cancer Center
Project Lead: Jian Hu, PHD
Grant Title: Epigenetic Regulation in Pediatric High-Grade Gliomas
Program Area: Pediatric Gliomas
Grant Type: UKF Seed Grant
Year Awarded: 2020
Amount: $50,000
Duration: 1 year

Summary: Pediatric brain tumors are the most common solid tumors in children, with approximately 5,000 new cases diagnosed per year in the United States. Around 17% of brain tumors in children age 0–14 years are high-grade gliomas (HGGs). Pediatric HGG is the most lethal cancer in children; the median survival duration of the children with HGG is only 12–15 months despite aggressive therapies. Pediatric brain tumors show distinct features from their adult counterparts, and no advanced therapy for the disease has been developed during the last 3 decades. Most recently, new driver mutations on an essential gene in pediatric brain tumor have been identified, which occur in about 50% of pediatric HGGs. However, the gliomagenic mechanism and the potential targeted therapies related with these mutations are still waiting to be identified. Neural stem cell (NSC) is a type of cell that has the ability to generate all kinds of neural cells in developing brain, and has been considered as the origin of gliomagenesis. We have engineered the first-of-its-kind mouse model by introducing one of these two mutations in NSCs of mouse brain, which generates spontaneous pediatric HGG that mimics human pediatric HGG. By applying multifaceted methods to analyze these tumors, we have identified the two key drivers, which highly express in human gliomas and are greatly associated with poorer patient survival. In this proposal, by taking advantage of the novel mouse models, we plan to illustrate the roles of these newly identified key players in gliomagenesis and try to design new therapeutic approaches by targeting these components to treat pediatric HGGs. This study will help us better understand how pediatric HGGs initiate and progress and will greatly expedite the development of new therapies for the pediatric HGGs.

Update: Epigenetic Regulation in Pediatric High-Grade Gliomas,” was awarded a R01 Grant from the National Institute of Health (NIH) for 5 years up to $250,000 per year. The data that was gained from the work on this 2020 Seed Grant helped pave the way to this next phase of study.