Peritumoral Reactive Astrocytes
Astrocytes stained with anti-GFAP PE-labeled antibody (red); neurons stained with anti-NeuN AlexaFluor488-labeled antibody (green). Double staining was performed by immunohistochemistry on a coronal section from mouse brain harvested 15 days after tumor cell implantation.
Defining the Role of Olig Genes in the Pathogenesis of Gliomas
Using a variety of molecular, cellular, and genetic techniques, we are studying the function of proteins that regulate the activity of genes in neural and tumor stem cells. Specifically we are interested in the role of Olig genes, in the biology of gliomas. By isolating glioma stem cells from fresh human surgical tissue and culturing
in vitro and
in vivo in mice we study the unique molecular and genetic biology of these cells in relation to the whole tumor.
Dr. Kesari and colleagues have recently shown that the same genetic regulator that triggers growth of stem cells during brain development, Olig2 (a transcription factor), also plays a central role in the development of malignant gliomas from glioma cancer stem cells. Olig2 is activated in the stem and progenitor cells found in the tumors. In a mouse model of malignant glioma, they found that taking away Olig2 stopped tumor formation in 91% of the animals. Their analysis of the role of Olig2 gene in both tumor cells and normal neural stem cells revealed that it plays a key role in enabling cell growth. Dr. Kesari's findings identify Olig2 as an important candidate for antitumor therapeutics. Further studies are ongoing to unravel the mechanism of Olig2's function in glioma stem cells and screening drugs that will block this process with eventual goal of killing glioma stem cells.