Identifying Epigenetic Mechanisms Impacting Neuroblastoma Genome Stability and Drug Response
Genome instability and drug resistance are hallmark features of cancer, especially neuroblastoma. We have recently uncovered the first enzyme KDM4A capable of generating site-specific copy gains of regions linked to drug resistance and hard to treat cancer, which provides a novel tool to carefully interrogate the molecular features affiliated with copy gains.
In this project, we are characterizing the genomic features that are important in protecting regions from undergoing KDM4A-dependent copy gains and rereplication. In addition to modulating copy number of regions affiliated with resistance, our data suggest that KDM4A expression levels will be a critical determinant in neuroblastoma cancer cell drug response. Therefore, we are using a large collection of drug screening data in neuroblastoma cell lines to facilitate the identification of therapeutics that are more or less effective based on KDM4A expression levels. These drug relationships will then be characterized in relation to KDM4A. Therefore, our proposed studies will shed light on basic regulatory mechanisms influencing genome organization and expression, while identifying novel therapeutic strategies to treat neuroblastoma patients.