Charles D. Stiles, PhD
Office phone: 617-632-3512
Preferred contact method: email
Area of Research
Genetics of Brain Development
Dana-Farber Cancer Institute
450 Brookline Avenue
Boston, MA 02215
BiographyDr. Stiles received his PhD in 1973 from the University of Tennessee at the Oak Ridge National Laboratories. Following his postdoctoral research at the University of California, San Diego, from 1973-1976, he joined the faculty of Harvard and DFCI, where he currently is co-chair of the Department of Cancer Biology. His laboratory is cloning and characterizing growth factor-responsive genes that regulate brain development.
- BBS Mentoring Award, Harvard Medical School, 2007
- BBS Teaching Award, Harvard Medical School, 2000
ResearchGenetics of Brain Development
Primary cancers of the brain are the third leading cause of cancer-related death among men 15 to 54 years of age and the fourth leading cause of death among women 15 to 34 years of age. Among children younger than 15, the impact of central nervous system cancer is even more pronounced. Primary brain tumors are actually the most common solid tumor of childhood and the second leading cause of cancer death after leukemia. For the past 15 years, our research group has focused on brain cancers. We are attacking this clinical problem by addressing a fundamental question in basic science: Which genes regulate the development of the normal brain? We currently are cloning and characterizing genes that "instruct" brain progenitor cells to develop into mature neurons, astrocytes, and oligodendrocytes - the cellular components of a mature brain. We reason that the genes that give rise to a normal, functioning brain are the same genes that give rise to cancer of the brain when their expression is perturbed. Given a defined genetic target, scientists can screen large libraries of chemically diverse compounds to identify drugs that interact with the protein encoded by that specific gene. These genetically targeted compounds are "smart drugs" that can kill tumor cells without collateral damage to normal cells. We also hypothesize that genetic perturbations within genes that regulate brain development may underlie a broader range of inborn brain dysfunctions including childhood mental retardation, Alzheimer's disease, and schizophrenia. Thus, fundamental work on the genetics of brain development conducted under the auspices of brain cancer research could eventually have impact on health problems outside the cancer field.
- Williams, B. P., J. K. Park, J. A. Alberta, S. G. Muhlebach, G. Y. Hwang, T. M. Roberts, and C. D. Stiles. A PDGF-regulated immediate early gene response initiates neuronal differentiation in ventricular zone progenitor cells. Neuron 18:553-62.
- Kilic, T., J. A. Alberta, P. R. Zdunek, M. Acar, P. Iannarelli, T. O'Reilly, E. Buchdunger, P. M. Black, and C. D. Stiles. Intracranial inhibition of platelet-derived growth factor-mediated glioblastoma cell growth by an orally active kinase inhibitor of the 2-phenylaminopyrimidine class. Cancer Res 60:5143-50.
- Lu, Q. R., L. Cai, D. Rowitch, C. L. Cepko, and C. D. Stiles. Ectopic expression of Olig1 promotes oligodendrocyte formation and reduces neuronal survival in developing mouse cortex. Nat Neurosci 4:973-4.
- Lu, Q. R., T. Sun, Z. Zhu, N. Ma, M. Garcia, C. D. Stiles, and D. H. Rowitch. Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte connection. Cell 109:75-86.
- Arnett, H. A., S. P. Fancy, J. A. Alberta, C. Zhao, S. R. Plant, S. Kaing, C. S. Raine, D. H. Rowitch, R. J. Franklin, and C. D. Stiles. bHLH transcription factor Olig1 is required to repair demyelinated lesions in the CNS. Science 306:2111-5.
- Gray, P. A., H. Fu, P. Luo, Q. Zhao, J. Yu, A. Ferrari, T. Tenzen, D. I. Yuk, E. F. Tsung, Z. Cai, J. A. Alberta, L. P. Cheng, Y. Liu, J. M. Stenman, M. T. Valerius, N. Billings, H. A. Kim, M. E. Greenberg, A. P. McMahon, D. H. Rowitch, C. D. Stiles, and Q. Ma. Mouse brain organization revealed through direct genome-scale TF expression analysis. Science 306:2255-7.
- Dahia, P. L., K. Hao, J. Rogus, C. Colin, M. A. Pujana, K. Ross, D. Magoffin, N. Aronin, A. Cascon, C. Y. Hayashida, C. Li, S. P. Toledo, and C. D. Stiles. Novel pheochromocytoma susceptibility loci identified by integrative genomics. Cancer Res 65:9651-8.
- Stiles, C. D., and D. H. Rowitch. Glioma stem cells: a midterm exam. Neuron 58:832-46.
- Sun, Y., D. H. Meijer, J. A. Alberta, S. Mehta, M. F. Kane, A. C. Tien, H. Fu, M. A. Petryniak, G. B. Potter, Z. Liu, J. F. Powers, I. S. Runquist, D. H. Rowitch, and C. D. Stiles. Phosphorylation state of Olig2 regulates proliferation of neural progenitors. Neuron 69:906-17.
- Mehta, S., E. Huillard, S. Kesari, C. L. Maire, D. Golebiowski, E. P. Harrington, J. A. Alberta, M. F. Kane, M. Theisen, K. L. Ligon, D. H. Rowitch, and C. D. Stiles. The central nervous system-restricted transcription factor Olig2 opposes p53 responses to genotoxic damage in neural progenitors and malignant glioma. Cancer Cell 19:359-71.
- Alberta, John, PhD
- Sun, Yu, MD, PhD
- Zhou, Jing, PhD