Eli E. Bar, MD

My laboratory is primarily focused on the identification and targeting of cancer-cell intrinsic signaling nodes which are activated by signals from the tumor microenvironment.

1. Cellular adaptation to hypoxia and nutrient deprivation orchestrated by hypoxia inducible factors (HIFs) and the MonoCarboxylate Transporter-4 (MCT4). We have recently reported that hypoxia increases the percentage of GSCs in GBM cultures and in primary tumors and implicated HIFs and MCT4 in this response. Hypoxia has also been shown to promote radiation resistance and tumor invasion, suggesting that an improved understanding of how reduced oxygenation and nutrient availability modulate the pathobiology of glioblastoma will be necessary if we are to effectively treat these universally fatal neoplasms. We are actively engaged in preclinical testing of pharmacological agents that target these pathways in glioblastoma.
2. Crosstalk between microenvironmental factors and “stemness” signaling pathways. We have previously implicated Hedgehog, Notch, and other developmentally significant signaling pathways in the initiation and progression of Medulloblastoma and Glioblastoma. Increasing evidence suggest these pathways may be regulated not only by intrinsic but also by microenvironmental factors. Targeting microenvironmental factors which contribute to the induction of these pathways may lead to novel therapeutic approaches against glioblastomas and other tumors.
3. Mechanisms of drug resistance. Using array CGH technology, we showed that alterations activating the oncogene BRAF are common in pediatric low grade gliomas (>60% of Pilocytic Astrocytomas). We are currently investigating mechanisms of drug resistance in this complex group of tumors.