Charles Dean Stiles
Charles Dean Stiles, Ph.D.
Professor of Neurobiology, Emeritus

We are currently focused on a pair of CNS-specific bHLH transcription factors known as Olig1 and Olig2. The two Olig genes map to within 40 kb of each other on human chromosome 21 within the Down syndrome critical region. During embryonic development and also in the postnatal brain, the two Olig genes are expressed in progenitor cells that give rise to oligodendrocytes and certain types of neurons (notably motor neurons). Beyond merely marking these cell types, targeted disruption of Olig1/2 in developing embryos disrupts patterning of the ventral spinal cord, ablates formation of oligodendrocytes throughout the CNS and prevents formation of motor neurons. The two Olig proteins are similar to each other within the DNA-targeting bHLH motif. Outside the bHLH domain however, Olig1 and Olig2 are very different proteins and this is reflected in non-overlapping biological functions. Olig1 function has been shown to be essential for the repair of demyelinating lesions in murine models of multiple sclerosis. Olig2 is expressed in the stem-like cells that are found in high-grade human gliomas and is essential for tumor formation in “genetically relevant” murine models of human glioma. Current activities in the Stiles lab are aimed at defining 1) structural features of the two Olig proteins that underlie their separate biological functions, 2) genetic targets of Olig genes and 3) key co-regulator proteins. A variety of methods are used towards these ends including mass spectroscopy, ChIP/Seq and high throughput RNAi screens.

"The two Olig genes map to within 40 kb of each other on human chromosome 21 within the Down syndrome critical region. During embryonic development and also in the postnatal brain, the two Olig genes are expressed in progenitor cells that give rise to oligodendrocytes and certain types of neurons (notably motor neurons)."

Publications View
Mitogenic and progenitor gene programmes in single pilocytic astrocytoma cells.
Authors: Authors: Reitman ZJ, Paolella BR, Bergthold G, Pelton K, Becker S, Jones R, Sinai CE, Malkin H, Huang Y, Grimmet L, Herbert ZT, Sun Y, Weatherbee JL, Alberta JA, Daley JF, Rozenblatt-Rosen O, Condurat AL, Qian K, Khadka P, Segal RA, Haas-Kogan D, Filbin MG, Suva ML, Regev A, Stiles CD, Kieran MW, Goumnerova L, Ligon KL, Shalek AK, Bandopadhayay P, Beroukhim R.
Nat Commun
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Clinical targeted exome-based sequencing in combination with genome-wide copy number profiling: precision medicine analysis of 203 pediatric brain tumors.
Authors: Authors: Ramkissoon SH, Bandopadhayay P, Hwang J, Ramkissoon LA, Greenwald NF, Schumacher SE, O'Rourke R, Pinches N, Ho P, Malkin H, Sinai C, Filbin M, Plant A, Bi WL, Chang MS, Yang E, Wright KD, Manley PE, Ducar M, Alexandrescu S, Lidov H, Delalle I, Goumnerova LC, Church AJ, Janeway KA, Harris MH, MacConaill LE, Folkerth RD, Lindeman NI, Stiles CD, Kieran MW, Ligon AH, Santagata S, Dubuc AM, Chi SN, Beroukhim R, Ligon KL.
Neuro Oncol
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A brain-penetrant RAF dimer antagonist for the noncanonical BRAF oncoprotein of pediatric low-grade astrocytomas.
Authors: Authors: Sun Y, Alberta JA, Pilarz C, Calligaris D, Chadwick EJ, Ramkissoon SH, Ramkissoon LA, Garcia VM, Mazzola E, Goumnerova L, Kane M, Yao Z, Kieran MW, Ligon KL, Hahn WC, Garraway LA, Rosen N, Gray NS, Agar NY, Buhrlage SJ, Segal RA, Stiles CD.
Neuro Oncol
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Population Control: Cortical Interneurons Modulate Oligodendrogenesis.
Authors: Authors: Bandopadhayay P, Stiles CD.
Neuron
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A Sequentially Priming Phosphorylation Cascade Activates the Gliomagenic Transcription Factor Olig2.
Authors: Authors: Zhou J, Tien AC, Alberta JA, Ficarro SB, Griveau A, Sun Y, Deshpande JS, Card JD, Morgan-Smith M, Michowski W, Hashizume R, James CD, Ligon KL, Snider WD, Sicinski P, Marto JA, Rowitch DH, Stiles CD.
Cell Rep
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Establishment and application of a novel patient-derived KIAA1549:BRAF-driven pediatric pilocytic astrocytoma model for preclinical drug testing.
Authors: Authors: Selt F, Hohloch J, Hielscher T, Sahm F, Capper D, Korshunov A, Usta D, Brabetz S, Ridinger J, Ecker J, Oehme I, Gronych J, Marquardt V, Pauck D, Bächli H, Stiles CD, von Deimling A, Remke M, Schuhmann MU, Pfister SM, Brummer T, Jones DT, Witt O, Milde T.
Oncotarget
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Copy-number and gene dependency analysis reveals partial copy loss of wild-type SF3B1 as a novel cancer vulnerability.
Authors: Authors: Paolella BR, Gibson WJ, Urbanski LM, Alberta JA, Zack TI, Bandopadhayay P, Nichols CA, Agarwalla PK, Brown MS, Lamothe R, Yu Y, Choi PS, Obeng EA, Heckl D, Wei G, Wang B, Tsherniak A, Vazquez F, Weir BA, Root DE, Cowley GS, Buhrlage SJ, Stiles CD, Ebert BL, Hahn WC, Reed R, Beroukhim R.
Elife
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Tyrosine receptor kinase B is a drug target in astrocytomas.
Authors: Authors: Ni J, Xie S, Ramkissoon SH, Luu V, Sun Y, Bandopadhayay P, Beroukhim R, Roberts TM, Stiles CD, Segal RA, Ligon KL, Hahn WC, Zhao JJ.
Neuro Oncol
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Challenges in Targeting a Basic Helix-Loop-Helix Transcription Factor with Hydrocarbon-Stapled Peptides.
Authors: Authors: Edwards AL, Meijer DH, Guerra RM, Molenaar RJ, Alberta JA, Bernal F, Bird GH, Stiles CD, Walensky LD.
ACS Chem Biol
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Gliomas "Dope Up" for Growth.
Authors: Authors: Paolella BR, Stiles CD.
Cancer Cell
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