Photo of Brian J. Druker, M.D.

Brian J. Druker M.D.

    • Professor of Medicine, Division of Hematology/Medical Oncology School of Medicine
    • Associate Dean, Oncology Office of the Dean School of Medicine
    • Director OHSU Knight Cancer Institute School of Medicine
    • JELD-WEN Chair of Leukemia Research
    • Cancer Biology Graduate Program School of Medicine
    • Program in Molecular and Cellular Biosciences School of Medicine

Dr. Druker's research focuses on activated tyrosine kinases with an emphasis on signal transduction and cellular transformation and the application of this knowledge to cancer therapies. The BCR-ABL oncogene is his lab's primary model system because of its central role in the pathogenesis of a human disease, chronic myeloid leukemia (CML). Numerous tyrosine phosphorylated proteins have been identified in BCR-ABL transformed cells and projects are ongoing to define their necessity for BCR-ABL function. These studies include mutational, biochemical and genetic approaches. Imatinib (Gleevec), a specific inhibitor of the ABL protein tyrosine kinase, has been proven to be an effective therapeutic agent in CML. However, it is not capable of eliminating all leukemic cells. In laboratory correlate studies done alongside imatinib clinical trials, Dr. Druker's lab learned that ABL kinase domain mutations are the most common mechanism of resistance to imatinib. Using this information, his team has evaluated several novel ABL inhibitors that are now available to treat patients with Gleevec resistance. Lastly, Dr. Druker's lab is performing screens for other tyrosine kinases that may be pathogenic in other leukemias and has developed functional assays that allow rapid target identification.

Education

  • M.D., University of California San Diego 1981
  • Residency:

    • Barnes Hospital, Washington University, St. Louis
  • Fellowship:

    • Medical oncology - Dana-Farber Cancer Institute, Harvard Medical School, Boston
  • Certifications:

    • American Board of Internal Medicine, 1984

Memberships and associations

  • Institute of Medicine: National Academy of Sciences
  • American Association of Physicians
  • National Academy of Sciences
  • American Society for Clinical Investigation
  • American Society of Hematology
  • American Society of Clinical Oncology
  • American Association for Cancer Research
  • American Association for the Advancement of Science
  • American Society for Microbiology
  • Children’s Oncology Group
  • The American Society for Cell Biology

Publications

  • "The negative systemic effect of BCGcw inoculated intraperitoneally - I. In vivo demonstration of intramuscular tumor growth enhancement with Morris hepatomas" Cancer Immunology and Immunotherapy April 1981
  • "Rapid T-cell receptor-mediated tyrosine phosphorylation of p120, an Fyn/Lck Src homology 3 domain-binding protein" Proceedings of the National Academy of Sciences of the United States of America May 10 1994
  • "Ligand independence of the T618I mutation in the colony-stimulating factor 3 receptor (CSF3R) protein results from loss of O-linked glycosylation and increased receptor dimerization" Journal of Biological Chemistry February 28 2014
  • "STI571" Current Oncology Reports May 2001
  • "All-trans-retinoic acid induces tyrosine phosphorylation of the CrkL adapter in acute promyelocytic leukemia cells" Experimental Hematology July 2000
  • "Inhibition of polysome assembly enhances imatinib activity against chronic myelogenous leukemia and overcomes imatinib resistance" Molecular and Cellular Biology October 2008
  • "Identification and characterization of two novel SH2 domain-containing proteins from a yeast two hybrid screen with the ABL tyrosine kinase" Oncogene  1997
  • "CAL-101, a p110δ selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability" Blood January 13 2011
  • "Progressive loss of epidermal growth factor receptor in a subpopulation of breast cancers" Molecular Cancer Therapeutics November 1 2007
  • "Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor" New England Journal of Medicine April 5 2001
  • "Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome" New England Journal of Medicine April 5 2001
  • "Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia" New England Journal of Medicine April 5 2001
  • "Rapid tyrosine phosphorylation and activation of Bruton's tyrosine/Tec kinases in platelets induced by collagen binding or CD32 cross-linking" Blood March 1 2000
  • "Small molecule inhibitor screen identifies synergistic activity of the bromodomain inhibitor CPI203 and bortezomib in drug resistant myeloma" Oncotarget  2015
  • "STI571" The Lancet Oncology December 1 2000
  • "RNAi-induced down-regulation of FLT3 expression in AML cell lines increases sensitivity to MLN518" Blood April 1 2005
  • "Direct binding of CRKL to BCR-ABL is not required for BCR-ABL transformation" Blood January 1 1997
  • "In vitro studies of the combination of imatinib mesylate (Gleevec) and arsenic trioxide (Trisenox) in chronic myelogenous leukemia" Experimental Hematology  2002
  • "TYK2-STAT1-BCL2 pathway dependence in T-cell acute lymphoblastic leukemia" Cancer Discovery May 2013
  • "Effects of plerixafor in combination with BCR-ABL kinase inhibition in a murine model of CML" Blood September 27 2012
  • "Bcr-Abl mutations, resistance to imatinib, and imatinib plasma levels [4] (multiple letters)" Blood September 1 2003
  • "Synergistic interactions between imatinib mesylate and the novel phosphoinositide-dependent kinase-1 inhibitor OSU-03012 in overcoming imatinib mesylate resistance" Blood May 15 2005
  • "The non-receptor tyrosine kinase Syk is a target of Cbl-mediated ubiquitylation upon B-cell receptor stimulation" EMBO Journal December 17 2002
  • "STI571, a tyrosine kinase inhibitor for the treatment of chronic myelogenous leukemia" Cancer Chemotherapy and Pharmacology  2001
  • "Monitoring CML patients responding to treatment with tyrosine kinase inhibitors" Blood July 1 2006
  • "The JAK2V617F activating mutation occurs in chronic myelomonocytic leukemia and acute myeloid leukemia, but not in acute lymphoblastic leukemia or chronic lymphocytic leukemia" Blood November 15 2005
  • "Corrigendum" EMBO Journal  1996
  • "AP24534, a Pan-BCR-ABL Inhibitor for Chronic Myeloid Leukemia, Potently Inhibits the T315I Mutant and Overcomes Mutation-Based Resistance" Cancer Cell November 6 2009
  • "Acute dasatinib exposure commits Bcr-Abl-dependent cells to apoptosis" Blood  2009
  • "Functional RNAi screen targeting cytokine and growth factor receptors reveals oncorequisite role for interleukin-2 gamma receptor in JAK3-mutation-positive leukemia" Oncogene June 4 2015

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