Joseph McCarty

The brain is the most vascularized organ in the human body. Its billions of neurons and glia are interconnected with an elaborate network of blood vessels that display many unique features, including a blood-brain barrier (BBB). The mechanisms by which cerebral endothelial cells properly integrate neural cues to control essential physiological processes such as angiogenesis and BBB homeostasis remain enigmatic. Over the past five years the major goals of my research program have been to (1) identify and characterize signaling pathways that couple glial cells to endothelial cells to control blood vessel functions in the brain; and (2) understand how these pathways are altered in brain pathologies, and particularly in the malignant cancer glioblastoma (GBM). Along these lines, my research group studies extracellular matrix (ECM) adhesion and signaling pathways that are required for normal brain vascular development, and how GBM cells exploit these pathways for selective growth and survival. We have developed various transgenic and knockout mouse models to identify and characterize how glial-endothelial cell interactions. In addition, using primary human tumor samples and xenograft mouse models, we have also discovered important pathways that drive GBM growth and invasion in the perivascular niche. Genomic-based strategies have also been used to identify and characterize additional angiogenic pathways that promote normal brain development and are deregulated in GBM. The long-term goals of my research program are to translate these fundamental research discoveries to clinical therapies to benefit patients with malignant brain cancer.