Brain tumors remain a deadly form of cancer. Our laboratory aims to elucidate the molecular machinery that drives the malignancy of brain tumor cells. Two major research areas of our group include:
1. Axon guidance molecules control cellular dynamics and invasiveness of brain tumor cells. To investigate the mechanisms that control the invasive migratory behavior of brain tumor cells, we are generating genetic mutations in human glioblastoma cells, focusing on axon guidance molecules and their downstream effectors. We are using in vitro culture systems and in vivo intracranial transplant paradigms to study cellular dynamics and migration of glioblastoma cells. A particular effort is on elucidating the role of Plexin-B2, an axon guidance receptor that plays an important role in nervous system development, and which is upregulated in glioblastoma, correlating with shorter patient survival.
2. Molecular reporters to study physiology of brain tumor cells. We are using genetic engineering to insert in human glioblastoma cells fluorescent protein reporters to study the physiological status of cells inside growing brain tumors. For example, we have inserted reporters for cell division (histone-2B-GFP) and hypoxia (HRE-UnaG). The use of fluorescent protein reporters allows us to study physiology of tumor cells in high resolution in intracranial transplants and in 3D glioblastoma organoid cultures. Cells can also be isolated and sorted according to their physiological status and analyzed for their molecular profile with next-generation sequencing. Characterizing quiescent and hypoxic cells will allow us to better understand and target brain tumor stem cells, a group of cells believed to be a special subpopulation with enhanced tumorigenic capacity and resistance to conventional therapy.
Friedel Lab website