Photo of Jeffrey W. Tyner, Ph.D.

Jeffrey W. Tyner Ph.D.

  • (503) 346-0603
    • Professor of Medicine School of Medicine
    • Cell and Developmental Biology Graduate Program School of Medicine
    • Cancer Biology Graduate Program School of Medicine
    • Program in Molecular and Cellular Biosciences School of Medicine

My research can be characterized by two primary interests: 1) identification of the genetic lesions underlying cancer pathogenesis for each cancer patient, and 2) identification of specific, gene-targeted therapies that can be individually tailored to cancer patients on the basis of their causative oncogenic lesions. Towards this end, I have developed two functional screening strategies making use of siRNA and small-molecule kinase inhibitor libraries to interrogate the genes and signaling pathways required for growth and viability of malignant cells. I have applied these techniques directly to primary cells from cancer patients to identify new oncogenes. It has also become clear that functional screening can only reveal part of the answer when used as a stand-alone technique. As such, I am integrating analysis of these same patient samples with a series of genomic techniques for the identification of point mutations, translocations, mis-splicing, or gene over-expression events. Simultaneous application of both functional and genomic screens will accelerate our understanding of the genes and pathways that contribute to neoplasia, such that cancer therapy can be individually tailored for each patient.

Areas of interest

  • Hematology/Oncology Kinase Signaling Genetics of Kinase Dysregulation Targeted Therapies
  • Personalized Medicine

Publications

  • "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
  • "Next-generation medicine" Clinical Cancer Research March 15 2013
  • "p38 MAPK inhibition suppresses the TLR-hypersensitive phenotype in FANCC and FANCA-deficient mononuclear phagocytes" Blood March 1 2012
  • "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
  • "Small molecule inhibitor screen identifies synergistic activity of the bromodomain inhibitor CPI203 and bortezomib in drug resistant myeloma" Oncotarget  2015
  • "TYK2-STAT1-BCL2 pathway dependence in T-cell acute lymphoblastic leukemia" Cancer Discovery May 2013
  • "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
  • "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
  • "Immunity, inflammation, and remodeling in the airway epithelial barrier" Physiological Reviews  2002
  • "Functional genomics for personalized cancer therapy" Science Translational Medicine July 2 2014
  • "Antagonism of SET using OP449 enhances the efficacy of tyrosine kinase inhibitors and overcomes drug resistance in myeloid leukemia" Clinical Cancer Research April 15 2014
  • "CYT387, a novel JAK2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms" Blood June 24 2010
  • "Belinostat and panobinostat (HDACI)" Journal of Cancer Research and Clinical Oncology September 2013
  • "Crosstalk between KIT and FGFR3 promotes gastrointestinal stromal tumor cell growth and drug resistance" Journal of Cancer Research March 1 2015
  • "FLT3 K663Q is a novel AML-associated oncogenic kinase" Leukemia November 2006
  • "An adaptive Src-PDGFRA-Raf axis in rhabdomyosarcoma" Biochemical and Biophysical Research Communications September 28 2012
  • "Phosphoproteomics microarray screen reveals novel interaction between MPL and tensin2" Cell Cycle August 15 2011
  • "Acute and chronic airway responses to viral infection" Annals of the American Thoracic Society  2005
  • "Apoptosis in the airways" American Journal of Respiratory Cell and Molecular Biology July 1 2003
  • "Corepressor Rcor1 is essential for murine erythropoiesis" Blood May 15 2014
  • "Potent activity of ponatinib (AP24534) in models of FLT3-driven acute myeloid leukemia and other hematologic malignancies" Molecular Cancer Therapeutics June 2011
  • "Ponatinib overcomes FGF2-mediated resistance in CML patients without kinase domain mutations" Blood March 6 2014
  • "The function of the pleckstrin homology domain in BCR-ABL-mediated leukemogenesis" Leukemia January 2010
  • "Dynamic and nuclear expression of PDGFRα and IGF-1R in alveolar rhabdomyosarcoma" Molecular Cancer Research November 2013
  • "TSLP signaling network revealed by SILAC-based phosphoproteomics." Molecular and Cellular Proteomics June 2012
  • "Oncogenic CSF3R mutations in chronic neutrophilic leukemia and atypical CML" New England Journal of Medicine  2013
  • "Comparison of methods to identify aberrant expression patterns in individual patients" Genome Medicine November 29 2013
  • "Heterogeneity of pancreatic cancer metastases in a single patient revealed by quantitative proteomics" Molecular and Cellular Proteomics November 1 2014
  • "Foretinib is a potent inhibitor of oncogenic ROS1 fusion proteins" Proceedings of the National Academy of Sciences of the United States of America November 26 2013
  • "Self-Enforcing Feedback Activation between BCL6 and Pre-B Cell Receptor Signaling Defines a Distinct Subtype of Acute Lymphoblastic Leukemia" Cancer Cell March 9 2015

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