Charles Dean Stiles

Charles Dean Stiles, PhD

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
MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism.
Authors: Authors: Bandopadhayay P, Ramkissoon LA, Jain P, Bergthold G, Wala J, Zeid R, Schumacher SE, Urbanski L, O'Rourke R, Gibson WJ, Pelton K, Ramkissoon SH, Han HJ, Zhu Y, Choudhari N, Silva A, Boucher K, Henn RE, Kang YJ, Knoff D, Paolella BR, Gladden-Young A, Varlet P, Pages M, Horowitz PM, Federation A, Malkin H, Tracy AA, Seepo S, Ducar M, Van Hummelen P, Santi M, Buccoliero AM, Scagnet M, Bowers DC, Giannini C, Puget S, Hawkins C, Tabori U, Klekner A, Bognar L, Burger PC, Eberhart C, Rodriguez FJ, Hill DA, Mueller S, Haas-Kogan DA, Phillips JJ, Santagata S, Stiles CD, Bradner JE, Jabado N, Goren A, Grill J, Ligon AH, Goumnerova L, Waanders AJ, Storm PB, Kieran MW, Ligon KL, Beroukhim R, Resnick AC.
Nat Genet
View full abstract on Pubmed
A Brain Tumor/Organotypic Slice Co-culture System for Studying Tumor Microenvironment and Targeted Drug Therapies.
Authors: Authors: Chadwick EJ, Yang DP, Filbin MG, Mazzola E, Sun Y, Behar O, Pazyra-Murphy MF, Goumnerova L, Ligon KL, Stiles CD, Segal RA.
J Vis Exp
View full abstract on Pubmed
Expression profiles of 151 pediatric low-grade gliomas reveal molecular differences associated with location and histological subtype.
Authors: Authors: Bergthold G, Bandopadhayay P, Hoshida Y, Ramkissoon S, Ramkissoon L, Rich B, Maire CL, Paolella BR, Schumacher SE, Tabak B, Ferrer-Luna R, Ozek M, Sav A, Santagata S, Wen PY, Goumnerova LC, Ligon AH, Stiles C, Segal R, Golub T, Grill J, Ligon KL, Chan JA, Kieran MW, Beroukhim R.
Neuro Oncol
View full abstract on Pubmed
Of Brains and Blood: Developmental Origins of Glioma Diversity?
Authors: Authors: Filbin MG, Stiles CD.
Cancer Cell
View full abstract on Pubmed
An amino terminal phosphorylation motif regulates intranuclear compartmentalization of Olig2 in neural progenitor cells.
Authors: Authors: Meijer DH, Sun Y, Liu T, Kane MF, Alberta JA, Adelmant G, Kupp R, Marto JA, Rowitch DH, Nakatani Y, Stiles CD, Mehta S.
J Neurosci
View full abstract on Pubmed
Pediatric low-grade gliomas: how modern biology reshapes the clinical field.
Authors: Authors: Bergthold G, Bandopadhayay P, Bi WL, Ramkissoon L, Stiles C, Segal RA, Beroukhim R, Ligon KL, Grill J, Kieran MW.
Biochim Biophys Acta
View full abstract on Pubmed
Olig1 function is required to repress dlx1/2 and interneuron production in Mammalian brain.
Authors: Authors: Silbereis JC, Nobuta H, Tsai HH, Heine VM, McKinsey GL, Meijer DH, Howard MA, Petryniak MA, Potter GB, Alberta JA, Baraban SC, Stiles CD, Rubenstein JL, Rowitch DH.
Neuron
View full abstract on Pubmed
New progenitors NESTIN(g) in the EGL.
Authors: Authors: Pak E, Segal RA, Stiles CD.
Nat Neurosci
View full abstract on Pubmed
Molecular imaging of drug transit through the blood-brain barrier with MALDI mass spectrometry imaging.
Authors: Authors: Liu X, Ide JL, Norton I, Marchionni MA, Ebling MC, Wang LY, Davis E, Sauvageot CM, Kesari S, Kellersberger KA, Easterling ML, Santagata S, Stuart DD, Alberta J, Agar JN, Stiles CD, Agar NY.
Sci Rep
View full abstract on Pubmed
Genomic analysis of diffuse pediatric low-grade gliomas identifies recurrent oncogenic truncating rearrangements in the transcription factor MYBL1.
Authors: Authors: Ramkissoon LA, Horowitz PM, Craig JM, Ramkissoon SH, Rich BE, Schumacher SE, McKenna A, Lawrence MS, Bergthold G, Brastianos PK, Tabak B, Ducar MD, Van Hummelen P, MacConaill LE, Pouissant-Young T, Cho YJ, Taha H, Mahmoud M, Bowers DC, Margraf L, Tabori U, Hawkins C, Packer RJ, Hill DA, Pomeroy SL, Eberhart CG, Dunn IF, Goumnerova L, Getz G, Chan JA, Santagata S, Hahn WC, Stiles CD, Ligon AH, Kieran MW, Beroukhim R, Ligon KL.
Proc Natl Acad Sci U S A
View full abstract on Pubmed