Charles D. Stiles
Department of Microbiology and Molecular Genetics
Dana Farber Cancer Institute
Department of Cancer Biology
Smith Research Building, Room 1070
44 Binney Street
Boston, MA 02115
Tel: (617) 632-3512
Fax: (617) 632-4663
Email: charles_stiles@.dfci.harvard.edu
4 postdoctoral fellows
The Stiles laboratory works on transcription factors that direct the fate choice of neural progenitor cells. For the past several years, they have focused considerable attention on a pair of CNS-specific basic helix-loop-helix transcription factors known as Olig1 and Olig2. These two structurally related transcription factors are encoded on human chromosome 21 within the Down syndrome critical region. During development the Olig genes are expressed in ventral neural progenitor cells that give rise to oligodendrocytes, and certain neural subtypes. The Olig1 gene is required for maturation of oligodendrocyte progenitors - a function that is graphically displayed in murine models of multiple sclerosis. The Olig2 gene maintains normal neural progenitors in a replication competent state during early CNS development. Malignant gliomas appear to co opt this cell cycle regulator function of Olig2 to sustain the growth of a highly tumorigenic subpopulation of “glioma stem cells”. Current activities in the Stiles lab are aimed at defining 1) the posttranslational modifications of Olig proteins that regulate their biological functions and 2) genetic targets of Olig genes. A variety of contemporary methods in molecular biology are used towards these ends including time of flight mass spectroscopy and “ChIP on chip” technology.
References:
- Lu QR, Sun T, Zhu Z, Ma N, Garcia M, Stiles CD, Rowitch DH. Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte connection. Cell 2002; 109, 75-86.
- Arnett HA, Fancy SPJ, Alberta JA, Zhao C, Plant SR, Kaing S, Raine CS, Rowitch DH, Frankin RJM and Stiles CD. The bHLH Transcription Factor Olig1 is Required for Repair of Demyelinated Lesions in the CNS. Science 2004; 17;306(5704):2111-5.
- 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(4):503-17.
- Stiles CD and Rowitch D. Glioma Stem Cells: A Midterm Exam. Neuron 2008; 58 (6): 832-846.
BBS webpage updated 12/02/2009