Epigenomic reprogramming in glioma
Coordinated epigenetic regulation enables cells to adopt specific gene expression programs to orchestrate normal differentiation and maintain cell fate. Gliomas are the most common type of brain cancer and exome-sequencing data has identified mutations in epigenetic regulators as a major driver of these tumors. However, it remains incompletely understood how these epigenetic drivers rewire the chromatin landscape and how this epigenetic dysregulation alters cellular phenotypes such as differentiation and immune evasion. In the Phillips Lab, we employ a number of cutting-edge techniques – from the development of forward genetics tools (i.e. CRISPR-Cas9 screening technology), epigenomic profiling, using neural stem cell models, and patient-derived models of glioma – to elucidate how epigenetic mechanisms contribute to gliomagenesis. Our long term research goal is to understand the how epigenetic pathways are rewired in brain cancer during tumorigenesis, therapy, and evasion of immunity.
Novel glioma therapeutics
Identifying therapeutic targets in brain cancer has remained a challenge with not a single targeted therapy showing consistent efficacy. Drawing from our mechanistic work to understand how epigenetic regulation is perturbed in brain cancer, we are interested in identifying epigenetic pathways which can be targeted in brain cancer. Additionally, we use unbiased approaches including high-throughput genetic and small molecule screens in patient-derived glioma cells, organoids and genetically engineered mouse models to identify pathways which are specifically required in brain cancer cells. Ultimately, our goal is to rapidly translate our findings into human clinical trials within the Brain Tumor Center here at the University of Pennsylvania.