Photo of Charles D. Stiles, PhD

Charles D. Stiles, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-3512
Fax: (617) 632-4663


charles_stiles@dfci.harvard.edu

Photo of Charles D. Stiles, PhD

Dana-Farber Cancer Institute
Phone: (617) 632-3512
Fax: (617) 632-4663


charles_stiles@dfci.harvard.edu

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Charles D. Stiles, PhD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Professor, Neurobiology, Harvard Medical School
  • Co-Chair, Cancer Biology, Dana-Farber Cancer Institute
  • Deputy Director, Mahoney Center for Neuro Oncology, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

Research Abstract

The Stiles laboratory studies basic principles of growth factor signal transduction in nerve cells and in the developing nervous system. Two examples of work in progress are as follows:

Growth Factor signal transduction through long axons.

In myelinated nerve cells, target-derived neurotrophins must communicate with a nucleus that can be more than a meter away. In collaboration with Dr. Rosalind Segal (Dept. of Pediatric Oncology, DFCI) we are learning how target-derived neurotrophins transmit information through long nerve axons.

Regulation of Neuronal Development by Platelet-Derived Growth Factor.

Neurons, oligodendrocytes and astrocytes in the central nervous system are thought to be derived from a pluripotential stem cell in the embryonic neural plate. Our laboratory has shown that uncommitted stem cells from the developing cortex of embryonic rats develop into neurons following exposure to platelet-derived growth factor (PDGF). The laboratory is using adenoviral vectors to probe the signal transduction pathways that regulate this PDGF-mediated developmental switch. In addition, we are using subtractive hybridization methods to isolate PDGF-responsive gene sequences from the uncommitted stem cells.

Publications

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  • 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. Clinical targeted exome-based sequencing in combination with genome-wide copy number profiling: precision medicine analysis of 203 pediatric brain tumors. 2017. PubMed
  • Bandopadhayay P, Stiles CD. Population Control: Cortical Interneurons Modulate Oligodendrogenesis. Neuron 2017; 94:415-417. PubMed
  • 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. A Sequentially Priming Phosphorylation Cascade Activates the Gliomagenic Transcription Factor Olig2. Cell Rep 2017; 18:3167-3177. PubMed
  • 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. Copy-number and gene dependency analysis reveals partial copy loss of wild-type SF3B1 as a novel cancer vulnerability. Elife 2017. PubMed
  • 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. A brain-penetrant RAF dimer antagonist for the noncanonical BRAF oncoprotein of pediatric low-grade astrocytomas. 2017. PubMed
  • 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. Tyrosine receptor kinase B is a drug target in astrocytomas. 2016. PubMed
  • 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. Establishment and application of a novel patient-derived KIAA1549:BRAF-driven pediatric pilocytic astrocytoma model for preclinical drug testing. 2016. PubMed
  • Edwards AL, Meijer DH, Guerra RM, Molenaar RJ, Alberta JA, Bernal F, Bird GH, Stiles CD, Walensky LD. Challenges in Targeting a Basic Helix-Loop-Helix Transcription Factor with Hydrocarbon-Stapled Peptides. ACS Chem Biol 2016. PubMed
  • Paolella BR, Stiles CD. Gliomas "Dope Up" for Growth. Cancer Cell 2016; 29:778-80. PubMed
  • 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. MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism. Nat Genet 2016; 48:273-82. PubMed
  • 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. Expression profiles of 151 pediatric low-grade gliomas reveal molecular differences associated with location and histological subtype. 2015. PubMed
  • Chadwick EJ, Yang DP, Filbin MG, Mazzola E, Sun Y, Behar O, Pazyra-Murphy MF, Goumnerova L, Ligon KL, Stiles CD, Segal RA. A Brain Tumor/Organotypic Slice Co-culture System for Studying Tumor Microenvironment and Targeted Drug Therapies. 2015. PubMed
  • Meijer DH, Sun Y, Liu T, Kane MF, Alberta JA, Adelmant G, Kupp R, Marto JA, Rowitch DH, Nakatani Y, Stiles CD, Mehta S. An amino terminal phosphorylation motif regulates intranuclear compartmentalization of Olig2 in neural progenitor cells. J Neurosci 2014; 34:8507-18. PubMed
  • Bergthold G, Bandopadhayay P, Bi WL, Ramkissoon L, Stiles C, Segal RA, Beroukhim R, Ligon KL, Grill J, Kieran MW. Pediatric low-grade gliomas: how modern biology reshapes the clinical field. Biochim Biophys Acta 2014; 1845:294-307. PubMed
  • 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. Olig1 function is required to repress dlx1/2 and interneuron production in Mammalian brain. Neuron 2014; 81:574-87. PubMed
  • 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. Genomic analysis of diffuse pediatric low-grade gliomas identifies recurrent oncogenic truncating rearrangements in the transcription factor MYBL1. Proc Natl Acad Sci U S A 2013; 110:8188-93. PubMed
  • 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. Molecular imaging of drug transit through the blood-brain barrier with MALDI mass spectrometry imaging. Sci Rep 2013; 3:2859. PubMed
  • Meijer DH, Kane MF, Mehta S, Liu H, Harrington E, Taylor CM, Stiles CD, Rowitch DH. Separated at birth? The functional and molecular divergence of OLIG1 and OLIG2. Nat Rev Neurosci 2012; 13:819-31. PubMed
  • Chi AS, Batchelor TT, Dias-Santagata D, Borger D, Stiles CD, Wang DL, Curry WT, Wen PY, Ligon KL, Ellisen L, Louis DN, Iafrate AJ. Prospective, high-throughput molecular profiling of human gliomas. J. Neurooncol. 2012; 110:89-98. PubMed
  • Zhou J, Stiles CD. Asleep at the switch: MEK kinases control transit to gliogenesis in developing cortex. Neuron 2012; 75:940-2. PubMed
  • Chaponis D, Barnes JW, Dellagatta JL, Kesari S, Fast E, Sauvageot C, Panagrahy D, Greene ER, Ramakrishna N, Wen PY, Kung AL, Stiles C, Kieran MW. Lonafarnib (SCH66336) improves the activity of temozolomide and radiation for orthotopic malignant gliomas. J. Neurooncol. 2011. PubMed
  • Sun Y, Meijer DH, Alberta JA, Mehta S, Kane MF, Tien AC, Fu H, Petryniak MA, Potter GB, Liu Z, Powers JF, Runquist IS, Rowitch DH, Stiles CD. Phosphorylation state of Olig2 regulates proliferation of neural progenitors. Neuron 2011; 69:906-17. PubMed
  • Mehta S, Huillard E, Kesari S, Maire CL, Golebiowski D, Harrington EP, Alberta JA, Kane MF, Theisen M, Ligon KL, Rowitch DH, Stiles CD. The central nervous system-restricted transcription factor Olig2 opposes p53 responses to genotoxic damage in neural progenitors and malignant glioma. Cancer Cell 2011; 19:359-71. PubMed
  • Qin Y, Yao L, King EE, Buddavarapu K, Lenci RE, Chocron ES, Lechleiter JD, Sass M, Aronin N, Schiavi F, Boaretto F, Opocher G, Toledo RA, Toledo SP, Stiles C, Aguiar RC, Dahia PL. Germline mutations in TMEM127 confer susceptibility to pheochromocytoma. Nat Genet 2010; 42:229-33. PubMed
  • Wen PY,Yung WK,Lamborn KR,Norden AD,Cloughesy TF,Abrey LE,Fine HA,Chang SM,Robins HI,Fink K,Deangelis LM,Mehta M,Di Tomaso E,Drappatz J,Kesari S,Ligon KL,Aldape K,Jain RK,Stiles CD,Egorin MJ,Prados MD. Phase II study of imatinib mesylate (Gleevec(R)) for recurrent meningiomas (North American Brain Tumor Consortium Study 01-08). Neuro-oncol 2009; 11:853-60. PubMed
  • Fu H, Cai J, Clevers H, Fast E, Gray S, Greenberg R, Jain MK, Ma Q, Qiu M, Rowitch DH, Taylor CM, Stiles CD. A genome-wide screen for spatially restricted expression patterns identifies transcription factors that regulate glial development. J Neurosci 2009; 29:11399-408. PubMed
  • Sauvageot CM,Weatherbee JL,Kesari S,Winters SE,Barnes J,Dellagatta J,Ramakrishna NR,Stiles CD,Kung AL,Kieran MW,Wen PY. Efficacy of the HSP90 inhibitor 17-AAG in human glioma cell lines and tumorigenic glioma stem cells. Neuro-oncol 2008; 11:109-21. PubMed
  • MacConaill LE, Campbell CD, Kehoe SM, Bass AJ, Hatton C, Niu L, Davis M, Yao K, Hanna M, Mondal C, Luongo L, Emery CM, Baker AC, Philips J, Goff DJ, Fiorentino M, Rubin MA, Polyak K, Chan J, Wang Y, Fletcher JA, Santagata S, Corso G, Roviello F, Shivdasani R, Kieran MW, Ligon KL, Stiles CD, Hahn WC, Meyerson ML, Garraway LA. Profiling critical cancer gene mutations in clinical tumor samples. PLoS ONE 2009; 4:e7887. PubMed
  • Stiles CD,Rowitch DH. Glioma stem cells: a midterm exam. Neuron 2008; 58:832-46. PubMed
  • Sauvageot CM, Kesari S, Stiles CD. Molecular pathogenesis of adult brain tumors and the role of stem cells. Neurol Clin 2007; 25:891-924, vii. PubMed
  • Kesari S, Jackson-Grusby L, Stiles CD. "Smad"eningly erratic: target gene methylation determines whether TGFbeta promotes or suppresses malignant glioma. Dev Cell 2007; 12:324-5. PubMed
  • Ligon KL, Huillard E, Mehta S, Kesari S, Liu H, Alberta JA, Bachoo RM, Kane M, Louis DN, Depinho RA, Anderson DJ, Stiles CD, Rowitch DH. Olig2-regulated lineage-restricted pathway controls replication competence in neural stem cells and malignant glioma. Neuron 2007; 53:503-17. PubMed
  • Wen PY, Yung WK, Lamborn KR, Dahia PL, Wang Y, Peng B, Abrey LE, Raizer J, Cloughesy TF, Fink K, Gilbert M, Chang S, Junck L, Schiff D, Lieberman F, Fine HA, Mehta M, Robins HI, DeAngelis LM, Groves MD, Puduvalli VK, Levin V, Conrad C, Maher EA, Aldape K, Hayes M, Letvak L, Egorin MJ, Capdeville R, Kaplan R, Murgo AJ, Stiles C, Prados MD. Phase I/II study of imatinib mesylate for recurrent malignant gliomas: North American Brain Tumor Consortium Study 99-08. Clin Cancer Res 2006; 12:4899-907. PubMed
  • Kesari S, Stiles CD. The Bad Seed: PDGF Receptors Link Adult Neural Progenitors to Glioma Stem Cells. Neuron 2006; 51:151-3. PubMed
  • Ligon KL, Kesari S, Kitada M, Sun T, Arnett HA, Alberta JA, Anderson DJ, Stiles CD, Rowitch DH. Development of NG2 neural progenitor cells requires Olig gene function. Proc Natl Acad Sci U S A 2006; 103:7853-8. PubMed
  • Sun T, Hafler BP, Kaing S, Kitada M, Ligon KL, Widlund HR, Yuk DI, Stiles CD, Rowitch DH. Evidence for motoneuron lineage-specific regulation of Olig2 in the vertebrate neural tube. Dev Biol 2006; 292:152-64. PubMed
  • Kesari S, Ramakrishna N, Sauvageot C, Stiles CD, Wen PY. Targeted molecular therapy of malignant gliomas. Curr Oncol Rep 2006; 8:58-70. PubMed
  • Dahia PL, Ross KN, Wright ME, Hayashida CY, Santagata S, Barontini M, Kung AL, Sanso G, Powers JF, Tischler AS, Hodin R, Heitritter S, Moore F, Dluhy R, Sosa JA, Ocal IT, Benn DE, Marsh DJ, Robinson BG, Schneider K, Garber J, Arum SM, Korbonits M, Grossman A, Pigny P, Toledo SP, Nose V, Li C, Stiles CD. A HIF1alpha regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas. PLoS Genet 2005; 1:72-80. PubMed
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DF/HCC members that share similar concepts* with Charles D. Stiles, PhD but have yet to coauthor a publication with this researcher.

* Concepts are MeSH terms, automatically derived from member publications

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