Photo of Jeffrey W. Tyner, Ph.D.

Jeffrey W. Tyner Ph.D.

  • (503) 346-0603
    • Associate 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

  • "Recent Progress in Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia." Current Hematologic Malignancy Reports  In: , 06.10.2017, p. 1-10.
  • "Molecularly targeted drug combinations demonstrate selective effectiveness for myeloid- and lymphoid-derived hematologic malignancies." Proceedings of the National Academy of Sciences of the United States of America In: , Vol. 114, No. 36, 05.09.2017, p. E7554-E7563.
  • "Recurrent cyclin D2 mutations in myeloid neoplasms." Leukemia In: , Vol. 31, No. 9, 01.09.2017, p. 2005-2008.
  • "Unpaired extracellular cysteine mutations of CSF3R mediate gain or loss of function." Cancer Research In: , Vol. 77, No. 16, 15.08.2017, p. 4258-4267.
  • "Kinase Inhibitor Screening in Myeloid Malignancies." Hematology/Oncology Clinics of North America In: , Vol. 31, No. 4, 01.08.2017, p. 693-704.
  • "Identification of a novel SYK/c-MYC/MALAT1 signaling pathway and its potential therapeutic value in Ewing sarcoma." Clinical Cancer Research  In: , Vol. 23, No. 15, 01.08.2017, p. 4376-4387.
  • "Stability of patient-specific features of altered DNA replication timing in xenografts of primary human acute lymphoblastic leukemia." Experimental Hematology In: , Vol. 51, 01.07.2017, p. 71-82.e3.
  • "Turning the tide in myelodysplastic/myeloproliferative neoplasms." Nature Reviews Cancer  In: , Vol. 17, No. 7, 01.07.2017, p. 425-440.
  • "Cholesterol esterification inhibition and imatinib treatment synergistically inhibit growth of BCR-ABL mutation-independent resistant chronic myelogenous leukemia." PLoS ONE  In: , Vol. 12, No. 7, e0179558, 01.07.2017.
  • "Identification of targeted therapies for rare adult mature T-cell leukemia using functional ex vivo screening of primary patient samples." American Journal of Hematology  In: , Vol. 92, No. 5, 01.05.2017, p. E64-E66.
  • "Identification of Interleukin-1 by Functional Screening as a Key Mediator of Cellular Expansion and Disease Progression in Acute Myeloid Leukemia." Cell Reports  In: , Vol. 18, No. 13, 28.03.2017, p. 3204-3218.
  • "Ex vivo drug response profiling detects recurrent sensitivity patterns in drug-resistant acute lymphoblastic leukemia." Blood  In: , Vol. 129, No. 11, 16.03.2017, p. e26-e37.
  • "UNC2025, a MERTK small-molecule inhibitor, is therapeutically effective alone and in combination with methotrexate in leukemia models." Clinical Cancer Research In: , Vol. 23, No. 6, 15.03.2017, p. 1481-1492.
  • "Genomics of chronic neutrophilic leukemia." Blood In: , Vol. 129, No. 6, 09.02.2017, p. 715-722.
  • "CPX-351 exhibits potent and direct ex vivo cytotoxicity against AML blasts with enhanced efficacy for cells harboring the FLT3-ITD mutation." Leukemia Research In: , Vol. 53, 01.02.2017, p. 39-49.
  • "Differentiation status of primary chronic myeloid leukemia cells affects sensitivity to BCR-ABL1 inhibitors." Oncotarget  In: , Vol. 8, No. 14, 2017, p. 22606-22615.
  • "Small molecule inhibitor screening identifified HSP90 inhibitor 17-AAG as potential therapeutic agent for gallbladder cancer." Oncotarget In: , Vol. 8, No. 16, 2017, p. 26169-26184.
  • "BCL6 promotes glioma and serves as a therapeutic target." Proceedings of the National Academy of Sciences of the United States of America In: , Vol. 114, No. 15, 2017.
  • "PlGF enhances TLR-dependent inflammatory responses in human mononuclear phagocytes." American Journal of Reproductive Immunology In: , 2017.
  • "FGF2 from marrow microenvironment promotes resistance to FLT3 inhibitors in acute myeloid leukemia." Cancer Research In: , Vol. 76, No. 22, 15.11.2016, p. 6471-6482.
  • "Discovery and functional characterization of a germline, CSF2RB-activating mutation in leukemia." Leukemia In: , Vol. 30, No. 9, 01.09.2016, p. 1950-1953.
  • "Targeting BCL-2 and ABL/LYN in Philadelphia chromosome-positive acute lymphoblastic leukemia." Science Translational Medicine In: , Vol. 8, No. 354, 354ra114, 31.08.2016.
  • "Ultrasensitive proteomic quantitation of cellular signaling by digitized nanoparticle-protein counting." Scientific Reports In: , Vol. 6, 28163, 20.06.2016.
  • "JAKed up phenotype of CEBPA-mutant AML." Blood In: , Vol. 127, No. 24, 16.06.2016, p. 2946-2947.
  • "Targeting super-enhancer-associated oncogenes in oesophageal squamous cell carcinoma." Gut  In: , 10.05.2016.
  • "Clonality of neutrophilia associated with plasma cell neoplasms : Report of a SETBP1 mutation and analysis of a single institution series." Leukemia and Lymphoma In: , Vol. 57, No. 4, 02.04.2016, p. 927-934.
  • "Alterations in acute myeloid leukaemia bone marrow stromal cell exosome content coincide with gains in tyrosine kinase inhibitor resistance." British Journal of Haematology  In: , Vol. 172, No. 6, 01.03.2016, p. 983-986.
  • "The colony-Stimulating factor 3 receptor T640N mutation is oncogenic, sensitive toJAKInhibition, and mimics T618i." Clinical Cancer Research In: , Vol. 22, No. 3, 01.02.2016, p. 757-764.
  • "Mutant calreticulin-expressing cells induce monocyte hyperreactivity through a paracrine mechanism." American Journal of Hematology  In: , Vol. 91, No. 2, 01.02.2016, p. 211-219.
  • "Identification and characterization of tyrosine kinase nonreceptor 2 mutations in leukemia through integration of kinase inhibitor screening and genomic analysis." Cancer Research In: , Vol. 76, No. 1, 01.01.2016, p. 127-138.

Additional information

Edit profile