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Charles Stiles, Ph.D.

Professor of Microbiology and Molecular Genetics

Dana-Farber Cancer Institute
Smith 1070
44 Binney St
Boston, MA 02115
Telephone: 617-632-3512
Fax: 617- 632-4663
Email: charles_stiles@dfci.harvard.edu
Predocs: 0 Postdocs: 8 Completed PhD's: 5

 

Neurons, oligodendrocytes and astrocytes in the developing mammalian cortex are thought to arise from smaller subsets of pluripotent progenitor cells. The broad goal of the Stiles laboratory is to define transcription factors that mediate the fate choice decision of neural progenitors. We are particularly interested in transcription factors that instruct formation of the two principle types of macroglia in the brain – oligodendrocytes and astrocytes.

In a “directed screen” we isolated a pair of novel new bHLH transcription factors that we have termed “OLIG1” and “OLIG2”. With collaborator David Rowitch at Children’s Hospital, we demonstrated that OLIG1 and OLIG2 direct formation of two clinically relevant neural cell types – motor neurons and oligodendrocytes (Lu, Cai et al. 2001; Lu, Sun et al. 2002; Arnett, Fancy et al. 2004).Work in progress is aimed at identifying partner proteins and posttranslational modifications that regulate Olig gene functions in the brain (Sun, Dong et al. 2003).

In collaboration with the laboratory of Qiufu Ma (Dana-Farber Cancer Institute) we have created a genome-wide atlas of transcription factor expression in the developing brain (Gray, Fu et al. 2004). The in situ images have been scanned into a computerized database that is accessible to the scientific community via the worldwide web.  Using this database in conjunction with hairpin RNAi expression vectors and other high throughput genetic methods, we are currently screening for transcription factors that regulate formation of astrocytes in the developing brain.

 

References:

  • Arnett, H. A., S. P. Fancy, et al. (2004). "bHLH transcription factor Olig1 is required to repair demyelinated lesions in the CNS." Science 306(5704): 2111-5.
  • Gray, P. A., H. Fu, et al. (2004). "Mouse brain organization revealed through direct genome-scale TF expression analysis." Science 306(5705): 2255-7.
  • Lu, Q. R., L. Cai, et al. (2001). "Ectopic expression of Olig1 promotes oligodendrocyte formation and reduces neuronal survival in developing mouse cortex." Nat Neurosci 4(10): 973-4.
  • Lu, Q. R., T. Sun, et al. (2002). "Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte connection." Cell 109(1): 75-86.
  • Cross-repressive interaction of the Olig2 and Nkx2.2 transcription factors in developing neural tube associated with formation of a specific physical complex." J Neurosci 23(29): 9547-56.