Identification and Validation of C11ORF95-RELA Interacting Proteins
Mentor: Dr. Stephen Mack
Ependymoma is an aggressive and chemo-resistant pediatric brain tumor, with treatment to this date remaining surgical resection and radiation. Compared to other pediatric cancers, there are drastically fewer targeted agents currently under evaluation in ependymoma clinical trials. Therefore, any therapeutic advancement for ependymoma has the potential to translate to a clinical trial setting and have a measured impact on patient care. Over 70% of supratentorial (ST) ependymoma are characterized by an oncogenic fusion between C11ORF95 and RELA. C11ORF95-RELA fusion is frequently the sole genetic driver detected in ST ependymoma, thus ranking this genomic event as a lead target for therapeutic investigation. RELA is a transcription factor central to mediating NF-kB pathway activation in processes such as inflammation, cellular metabolism, and chemotaxis. Whether C11ORF95-RELA hyper-activates the NF-kB pathway during ependymoma development and is required for tumor maintenance is unclear. How C11ORF95-RELA protein expression directly modulates the epigenome and transcriptome is unknown. The capacity for targeting C11ORF95-RELA protein and/or downstream transcriptional targets has not yet been investigated. We have recently generated mass spectrometry analysis of C11ORF95-RELA interacting proteins. Understanding the relevance of top protein interactions with C11ORF95-RELA may provide insight into the mechanisms that drive cellular growth and tumorigenesis. We will work this summer to validate lead protein interactions with C11ORF95-RELA.
