THE PETRITSCH BRAIN TUMOR STEM CELL AND MODELS RESEARCH LAB
The Petritsch lab broadly investigates underlying causes for the intra-tumoral heterogeneity and immune suppression in brain tumors from a developmental neurobiology point of view. Defects in cell fate control could explain many key defects present in brain tumors and an understanding of how brain cells control the fate of their progeny may identify novel points of vulnerabilities to target with therapeutics. Of special emphasis, we study the establishment of cell fates within normal hierarchical brain lineages for comparison to the dysregulated cell-fate hierarchies seen in brain tumors. Our lab was the first to demonstrate that normal adult oligodendrocyte progenitor cells (OPCs) undergo asymmetric divisions to make cell fate decisions, i.e. to generate OPCs as well as differentiating cells each time they divide. Drawing from these data, we investigate whether brain tumors divide along hierarchical lineages and how oncogenic mutations might affect cell fate decisions within these hierarchies. A major line of investigation in our lab focuses on whether defects in the asymmetric division lead to aberrant cell fate decisions that cause the paradigm mixed-lineage phenotypes and the intra-tumoral heterogeneity present across tumors.
To study the interactions between tumor cells and the immune system, we have developed and utilized transplantable mouse glioma models. We are tasked to facilitate and coordinate the distribution of fresh tissue from the neurosurgery operating room and have access to fresh brain tissue from patient surgeries, from which we prepare cell culture models for brain tumors and normal progenitors. We complement our work with human cells with studies in genetically engineered mouse models of gliomagenesis to conduct molecular, cellular, and bioinformatic analyses.