Neuropathology

Neuropathology faculty have funded research programs in Alzheimer's disease, frontotemporal dementia and developmental biology. Our research supports the Mesulam Institute for Cognitive Neurology & Alzheimer's Disease and the Lou and Jean Malnati Brain Tumor Institute of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

Learn more about our work below.

Daniel Brat Lab
Mechanisms underlying glioblastoma progression and regulators of asymmetric cellular division in glioblastoma stem cells.

Research Description

Mechanisms Underlying Glioblastoma Progression

We investigate mechanisms of progression to glioblastoma (GBM), the highest-grade astrocytoma, including genetics, hypoxia and angiogenesis. Progression is characterized by tumor necrosis, severe hypoxia and microvascular hyperplasia, a type of angiogenesis. We propose that vaso-occlusion and intravascular thrombosis within a high-grade glioma result in hypoxia, necrosis and hypoxia-induced microvascular hyperplasia in the tumor periphery, leading to outward neoplastic expansion. Since the pro-thrombotic protein tissue factor is upregulated in gliomas, we investigate mechanisms of increased expression and pro-coagulant effects.

In Silico Brain Tumor Research

We initiated an In Silico Center for Brain Tumor Research to investigate the molecular correlates of pathologic, radiologic and clinical features of gliomas using pre-existing databases, including The Cancer Genome Atlas (TCGA) and Rembrandt. Using datasets and image analysis algorithms, we study whether elements of the tumor microenvironment, such as tumor necrosis, angiogenesis, inflammatory infiltrates and thrombosis, may correlate with gene expression subtypes in TCGA gliomas. We have also demonstrated the clinical relevance of TCGA subclasses within lower-grade gliomas using the Rembrandt dataset.

Regulators of Asymmetric Cellular Division in Glioblastoma Stem Cells

We study mechanisms that confer specialized biologic properties to glioma stem cells (GSC) in GBM. The Drosophila brain tumor (brat) gene normally regulates asymmetric cellular division and neural progenitor differentiation in the central nervous system of flies and, when mutated, leads to a massive brain containing only neuroblastic cells with tumor-like properties. We study the human homolog of Drosophila brat, Trim3, for its role in regulating asymmetric cell division and stem-like properties in GSCs. Trim3 may exert its effects through repression of c-Myc.

For more information, visit the faculty profile of Daniel Brat, MD, PhD, or the Brat Lab website.