A5070720142- RNA modifications and cancer
- RNA Research and Splicing
- Pluripotent Stem Cells Research
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- Renal and related cancers
Fred Hutch Cancer Center
2013-2015
To identify therapeutic targets for glioblastoma (GBM), we performed genome-wide CRISPR-Cas9 knockout (KO) screens in patient-derived GBM stem-like cells (GSCs) and human neural stem/progenitors (NSCs), non-neoplastic stem cell controls, genes required their vitro growth. Surprisingly, the vast majority GSC-lethal hits were found outside of molecular networks commonly altered GSCs (e.g., oncogenic drivers). In vivo validation GSC-specific revealed several strong hits, including wee1-like...
To identify key regulators of human brain tumor maintenance and initiation, we performed multiple genome-wide RNAi screens in patient-derived glioblastoma multiforme (GBM) stem cells (GSCs). These identified the plant homeodomain (PHD)-finger domain protein PHF5A as differentially required for GSC expansion, compared with untransformed neural (NSCs) fibroblasts. Given PHF5A's known involvement facilitating interactions between U2 snRNP complex ATP-dependent helicases, examined...