Research Summary
Dr. Eberhart and his lab members study the molecular genetics of medulloblastoma, low grade glioma, glioblastoma, uveal melanoma and other tumors of the brain and eye. One major focus is on Notch and other pathways which play a key role in both normal development and in neoplasia. They are currently analyzing the long terms effects of Notch blockade on cancer stem cells in brain and eye tumors, how therapeutic resistance emerges, and the basis of the sometimes antagonistic effects of various Notch receptors. They are also examining the role of c-Myc in the stem cell phenotype of cancer. Identifying novel genetic changes in ocular surface tumors and other poorly understood neoplasms represents another focus.
Lab
Dr. Eberhart works closely with Drs.Rodriguez and Raabe in a multidisciplinary research group. Their studies use our understanding of normal development to guide investigation of the neoplastic process. They have implicated Hedgehog, Notch and other developmentally significant signaling cascades in the initiation and ongoing growth of brain tumors. They are also engaged in preclinical testing of pharmacological agents that target multiple pathways in brain and eye tumors. To accomplish this they have generated new tumor models from surgical specimens and by making relevant oncogenic changes in progenitor cells. A related area of interest in the lab is the relationship between stem cells and cancer. The possibility that specific types of transformed stem cells represent the origins of brain and eye tumors, as well as the hypothesis that “cancer stem cells” are required for long-term tumor self renewal and growth, are both active areas of investigation.
Lab Website: Eberhart, Rodriguez and Raabe Lab
Selected Publications
Raabe EH, Lim KS, Kim JM, Meeker A, Mao XG, Nikkhah G, Maciaczyk J, Kahlert U, Jain D, Bar E, Cohen KJ, Eberhart CG. BRAF Activation Induces Transformation and Then Senescence in Human Neural Stem Cells: A Pilocytic Astrocytoma Model. Clin Cancer Res. 2011;17(11):3590-9
Pierfelice TJ, Schreck KC, Dang L, Asnaghi L, Gaiano N, Eberhart CG. Notch3 Activation Promotes Invasive Glioma Formation in a Tissue Site-Specific Manner. Cancer Res 2011; 71;1115-25.101.
Chu Q, Orr BA, Semenkow S, Bar EE, Eberhart CG. Prolonged Inhibition of Glioblastoma Xenograft Initiation and Clonogenic Growth following In Vivo Notch Blockade. Clin Cancer Res 2013;19(12):3224-33.
Asnaghi L, Lin MH, Lim KS, Lim KJ, Tripathy A, Wendeborn M, Merbs SL, Handa JT, Sodhi A, Bar EE, Eberhart CG. Hypoxia promotes uveal melanoma invasion through enhanced Notch and MAPK activation. PLoS One. 2014;9(8):e105372
Hanaford AR, Archer TC, Price A, Kahlert UD, Maciaczyk J, Nikkhah G, Kim JW, Ehrenberger T, Clemons PA, Dančík V, Seashore-Ludlow B, Viswanathan V, Stewart ML, Rees M, Shamji AF, Schreiber SL, Fraenkel E(, Pomeroy SL, Mesirov JP, Tamayo P, Eberhart CG*, Raabe EH* (*corresponding authors). DiSCoVERing innovative therapies for rare tumors: combining genetically accurate disease models with in silico analysis to identify novel therapeutic targets. Clin Cancer Res. 2016
