Daniel J. Brat, MD, PhD
Photo: Daniel J. Brat

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Elected 2014

Dr. Brat directs a basic and translational research lab that investigates mechanisms of glioma progression, including contributions of genetics, tumor microenvironment, and stem cells. One central focus has been to uncover mechanisms by which hypoxia develops in malignant gliomas and to demonstrate its downstream functional significance. Investigations of vaso-occlusion and intravascular thrombosis within malignant gliomas have suggested they are initiators and propagators of hypoxia, necrosis, and hypoxia-induced microvascular hyperplasia, which in turn drive neoplastic expansion rapidly outward. His research takes aim at the unproven and unsatisfying concept that “cancers outgrow their blood supply” and suggests that cancers grow in a manner that compromises their perfusion. He also studies mechanisms that confer specialized biologic properties to glioma stem cells (GSCs). The Drosophila brain tumor (brat) gene normally regulates asymmetric cellular division and neural progenitor differentiation in the CNS of flies and, when mutated, leads to a massive brain containing only neuroblastic cells with tumor-like properties. Dr. Brat studies the human orthologs of brat, as well as other related genes, that regulate asymmetric cell division and stem-like properties in GSCs. He has initiated an In Silico Center for Brain Tumor Research to investigate molecular correlates of pathologic, radiologic, and clinical features of human gliomas using comprehensive genomic databases, including as The Cancer Genome Atlas (TCGA), and bioinformatics approaches. Using datasets and image analysis algorithms, he studies whether elements of the tumor microenvironment, such as necrosis, angiogenesis, and inflammatory infiltrates, correlate with gene expression subtypes, genetics, or microRNA expression.