Multiomic Characterization of Cell State Heterogeneity in Human Brain Tumors

Tumors are no longer thought of as clonal expansions driven solely by genetic events. In reality, cancers are made up of multiple tumor cell states that are defined by transcriptional and epigenetic features superimposed on a mutational background. By integrating multiple types of single cell profiling (transcriptome, chromatin accessibility, histone modification specific profiling) we seek to better understand how cell states change over time and under therapeutic pressure. In addition, we attempt to model tumor evolutionary responses using patient derived model systems (specifically xenografts and tumor slice cultures) that more faithfully recapitulate the cell state heterogeneity seen in patients. Ultimately we hope to derive insights from single cell profiling that will lead to cell state directed therapeutic approaches to GBM and other malignancies.