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Email ceberha@jhmi.edu
Phone (410) 502-5185

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Opthalmic Pathology


Charles G. Eberhart, M.D., Ph.D.

Director, Division of Neuropathology
Primary Appointment in Pathology
Member, Graduate Program in Pathobiology


My research focuses on the pathology and genetics of brain and eye tumors. We have studied the role played by the Wnt, Notch and Hedgehog pathways in medulloblastoma and other embryonal tumors as well as malignant gliomas and uveal melanoma. These pathways regulate neural stem cell identity, and we have shown that Notch and Hedgehog are required in stem-like malignant glioma and medulloblastoma cells (“cancer stem cells”) as well. Our demonstration that pharmacological inhibition of either Notch or Hedgehog activity depletes stem-like cells from tumor cultures and slows or prevents clonogenic growth and xenograft initiation has helped to provide a rational for trials of Notch and Hedgehog inhibitors currently underway in children and adults. We also work on the effects of hypoxia, the pathobiology of low grade gliomas in the brain, and melanomas in the eye. I practice as a diagnostic pathologist, and pursue clinical/translational studies in which we seek to associate molecular changes in tumors with pathological subtype or clinical outcome.

Publications
Rodriguez FJ, Orr BA, Ligon KL, Eberhart CG. Neoplastic cells are a rare component in human glioblastoma microvasculature. Oncotarget 2012;3:98-106.

Asnaghi L, Ebrahimi KB, Schreck KC, Bar EE, Coonfield ML, Bell WR, Handa J, Merbs SL, Harbour JW, Eberhart CG. Notch signaling promotes growth and invasion in uveal melanoma. Clin Cancer Res 2012;18(3):654-65.

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.

Rajaii F, Asnaghi L, Enke R, Merbs SL, Handa JT, Eberhart CG. The demethylating agent 5-Aza reduces the growth, invasiveness, and clonogenicity of uveal and cutaneous melanoma. Invest Ophthalmol Vis Sci 2014;55(10):6178-86.

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. PMCID: PMC4148307

Kahlert UD, Suwala AK, Raabe EH, Siebzehnrubi FA, Suarez MJ, Orr BA, Bar EE, Maciaczyk J, Eberhart CG. ZEB1 promotes invasion in human fetal neural stem cells and hypoxic glioma neurospheres. Brain Pathol 2014 Dec 17. [Epub ahead of print]. PMID: 25521330

Lim KJ, Brandt WD, Heth JA, Muraszko KM, Fan X, Bar EE, Eberhart CG. Lateral inhibition of Notch signaling in neoplastic cells. Oncotarget 2015 Jan 30;6(3):1666-77. PMID: 25557173

Kahlert UD, Suwala AK, Koch K, Natsumeda M, Orr BA, Hayashi M, Maciaczyk J, Eberhart CG. Pharmacologic Wnt Inhibition Reduces Proliferation, Survival, and Clonogenicity of Glioblastoma Cells. J Neuropathol Exp Neurol. 2015 Sep;74(9):889-900

Kahlert UD, Cheng M, Koch K, Marchionni L, Fan X, Raabe EH, Maciaczyk J, Glunde K, Eberhart CG. Alterations in cellular metabolome after pharmacological inhibition of Notch in glioblastoma cells. Int J Cancer. 2015 Sep 30. Epub ahead of print.



 


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