DF/HCC Program Affiliation

Cancer Genetics
Neuro-Oncology

Research Abstract

‘Glioma stem cells’ are the most tumorigenic population of glioma cells and are thought to contribute to glioma initiation, maintenance, and resistance to therapy. Glioma stem cells share many phenotypic and molecular features with neural stem cells, however the biological processes that regulate glioma stem cells are poorly understood. Since epigenetic information contained within chromatin is critical to the function of embryonic and adult stem cells, we reasoned that aberrant chromatin regulation contributes to the malignant phenotype of glioma stem cells. Hence, our overall goal is to characterize the global chromatin state of glioma stem cells and use this data to gain a systems level understanding of how aberrant chromatin structure contributes to gliomagenesis. Recent development of high-throughput sequencing-based technologies has enabled high resolution, genome-wide characterization of chromatin structure in human cells. Using the ‘ChIP-Seq’ method, we are generating genome-wide ‘chromatin state maps’ of human embryonic stem cells, neural progenitor cells, astrocytes, and glioma stem cells. Our initial comparative analyses of the epigenomes of these cells demonstrate widespread deregulation of several key covalent histone modifications in glioma stem cells. Using novel computational analyses we are characterizing chromatin pathways that may contribute the malignant phenotype in glioma stem cells. Using these methods, we ultimately aim to identify novel markers of glioma stem cells and produce novel targets for therapeutic intervention.

Publications

• Chi AS,Bernstein BE.Developmental biology. Pluripotent chromatin state.Science 2009 Jan 9;323(5911):220-1.
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• Ku M,Koche RP,Rheinbay E,Mendenhall EM,Endoh M,Mikkelsen TS,Presser A,Nusbaum C,Xie X,Chi AS,Adli M,Kasif S,Ptaszek LM,Cowan CA,Lander ES,Koseki H,Bernstein BE.Genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains.PLoS
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• Chi A, Norden AD, Wen PY.Inhibition of angiogenesis and invasion in malignant gliomas.Expert Rev Anticancer Ther 2007 Nov;7(11):1537-60.
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• Chi AS, Wen PY.Inhibiting kinases in malignant gliomas.Expert Opin Ther Targets 2007 Apr;11(4):473-96.
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