Brian J. Druker

Joint Professor, Cell and Developmental Biology

The work in my laboratory has focused on the studies of activated tyrosine kinases with emphasis on their role in signal transduction and cellular transformation. We have been using the BCR-ABL oncogene as a model system because of its central role in the pathogenesis of a human disease, chronic myelogenous leukemia (CML). Several approaches are being taken to study this oncogene within the general framework of attempting to determine the substrates of this activated tyrosine kinase. A mutagenic analysis of BCR-ABL is being performed in order to correlate the pattern of phosphotyrosine containing proteins with biologic properties. As substrates are identified they are analyzed to determine their necessity for the transforming abilities of BCR-ABL. This is accomplished by determining the site of interaction between the substrate and BCR-ABL, mutating this site, and assaying for effects on BCR-ABL function. We are using mouse models and murine cell lines deficient in these proteins to assess their role in BCR-ABL mediated transformation. More recently we have turned our interests to the use of molecularly targeted therapies, such as the selective inhibitor of the BCR-ABL kinase, STI571, or Gleevec, which has just been approved by the FDA for treatment of CML. Based on the substrates identified above, we are using patient samples to analyze the mechanism of response to STI571. Finally, we are addressing ways to predict response and potential mechanisms of resistance to STI in patient samples using gene expression techniques and genetic analysis.

Druker, B.J., et al. (2001) Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in Chronic Myeloid Leukemia. New England Journal of Medicine 344:1031-7.

Druker, B.J., et al. (1996) Effects of a selective inhibitor of the Abl tyrosine kinase on growth of BCR-ABL positive cells. Nature Medicine 2:561-6.

Bhat, A., Johnson, K.J., Oda, T., Corbin, A. and Druker, B.J. (1998) Interactions of p62DOK with p210BCR-ABL and BCR-ABL associated proteins. J. Biol. Chem. 273:32360-8.

To contact Dr. Druker directly: drukerb@ohsu.edu