We have elucidated the role in Notch in cancer and demonstrated that Notch drives metastatic growth by providing cancer cells with metabolic flexibility to survive fluctuations in the tumormicroenvironment. We have also identified a novel regulatory mechanisms of Notch in the regulation of inflammatory cytikines which stimulate cancer cell growth and inflammatory cells. To circumvent the side effects associated with the use of Notch inhibitors we have developed a nanoparticle based drug delivery vehicle for tumor targeted delivery. We have identified novel modulators of Notch in stem cells and demonstrated that astrocytes in the brain are important regulators of neuronal stem cell differentiation upon trauma and this regulation is mediated by Notch. The process requires proper trafficking and localization of the Notch ligands in astrocytes something which is governed by vimentin, a cytoskeletal protein of significance for tumor invasion and is upregulated in metastatic cancers.