Biomedical Sciences Graduate Program | University of California, San Francisco

C. David James, PhD
CNS Tumor Molecular Biology and Therapeutic Testing

Selected Publications | Complete Publications

phone	(415) 476-5876
email	david.james@ucsf.edu
additional websites	Neurological Surgery
secondary research affiliation	Human Genetics

The broad-based objectives of my laboratory's research are to increase our understanding of the molecular biology underlying the development of central nervous system cancer, and to apply this knowledge towards improved outcomes for brain tumor patients. Within this framework, the laboratory has maintained focus on two specific areas of neuro-oncology research:

1) Analysis of mutant epidermal growth factor receptors in malignant gliomas . In addition to its amplification, the EGFR gene is frequently mutated in malignant gliomas. These mutations result in two classes of aberrant receptor: those having extracellular domain alterations (deletion or missense) and those having deletions of intracellular domain sequences. The functional and biological consequences of these mutations have been and continue to be subjects of research interest for the laboratory.

2) Rodent model testing of experimental therapies . The number of anti-cancer therapeutics, combination therapies, and therapy regimen variations to consider for use in the treatment of cancer patients is already substantial and is rapidly increasing. A necessary intermediate between cell culture assessment of therapy activity and assessment of patient benefit through clinical trials involves therapeutic testing in animal models. The laboratory has established an intracranial xenograft panel approach for pre-clinical testing of malignant glioma candidate therapies, and we are adapting this system for high throughput therapy screening that will, in turn, expedite the identification of the most promising approaches for treating patients. With respect to this goal, we are extensively utilizing and evaluating bioluminescence imaging for its full range of application.

Selected Publications

Frederick L, Wang XY, Eley G, James CD . Diversity and frequency of epidermal growth factor receptor mutations in human glioblastomas. Cancer Res 2000;60:1383-7.

Pandita A, Aldape KD, Zadeh G, Guha A, James CD . Contrasting in vivo and in vitro fates of glioblastoma cell subpopulations with amplified EGFR. Genes Chromosomes Cancer 2004;39:29-36.

Nakamura T, Peng KW, Harvey M, Greiner S, Lorimer IA, James CD , Russell SJ. Rescue and propagation of fully retargeted oncolytic measles viruses. Nat Biotechnol 2005;23:209-14.

Giannini C, Sarkaria JN, Saito A, Uhm JH, Galanis E, Carlson BL, Schroeder MA, James CD . Patient tumor EGFR and PDGFRA gene amplifications retained in an invasive intracranial xenograft model of glioblastoma multiforme. Neuro-oncol 2005;7:164-76.

Sarkaria JN, Carlson BL, Schroeder MA, Grogan P, Brown PD, Giannini C, Ballman KV, Kitange GJ, Guha A, Pandita A, James CD . Use of an orthotopic xenograft model for assessing the effect of epidermal growth factor receptor amplification on glioblastoma radiation response. Clin Cancer Res 2006;12:2264-71.

Sarkaria JN, Yang L, Grogan PT, Kitange GJ, Carlson BL, Schroeder MA, Galanis E, Giannini C, Wu W, Dinca EB, and James CD. Identification of Molecular Characteristics Correlated with Glioblastoma Sensitivity to EGFR Kinase Inhibition Through Use of an Intracranial Xenograft Test Panel. Mol Cancer Ther 6:1167-74, 2007.

Dinca EB, Lu K, Sarkaria J, Pieper RO, Prados MD, Haas-Kogan D, VandenBerg SR, Berger MS, and James CD. p53 Small Molecule Inhibitor Enhances Temozolomide Cytotoxic Activity against Intracranial Glioblastoma Xenografts. Cancer Research 68:10034-39, 2008.

Hodgson JG, Yeh R-F, Ray A, Wang NJ, Smirnov I, Yu M, Hariono S, Silber J, Feiler HS, Gray JW, Spellman PT, VandenBerg SR, Berger MS, and James CD. Comparative analyses of gene copy number and mRNA expression in GBM tumors and GBM xenografts. Neuro-oncology, Epub ahead of print, PMID 19139420, 2009.

information last updated August 2009