RNAi Screening Core

In the fullness of time, small molecule inhibitors of BRAF may be used for the treatment of BRAF mutant pediatric LGAs. However, multiple protein kinases have been shown to be co-activated in high-grade adult gliomas, and this is likely to be the case in BRAF-transformed pediatric astrocytomas as well. Complimentary signaling pathways are both an obstacle and an opportunity for targeted therapy strategies. An RNAi screening core will allow us to conduct a kinome-wide genetic screen for additional “druggable” protein kinases that cooperate with BRAF to dysregulate the proliferation of normal neural progenitor cells.  In addition RNAi screening complements DNA sequencing as a route to knowledge about other kinds of genes (e.g., GTP-binding proteins, transcription factors) that might underlie these tumors.