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

  • "Maintenance and pharmacologic targeting of ROR1 protein levels via UHRF1 in t(1;19) pre-B-ALL." Oncogene In: , 30.05.2018, p. 1-12.
  • "Targeting of colony-stimulating factor 1 receptor (CSF1R) in the CLL microenvironment yields antineoplastic activity in primary patient samples." Oncotarget In: , Vol. 9, No. 37, 15.05.2018, p. 24576-24589.
  • "Disparate effects of Shb gene deficiency on disease characteristics in murine models of myeloid, B-cell, and T-cell leukemia." Tumor Biology  In: , Vol. 40, No. 4, 01.04.2018.
  • "A novel AGGF1-PDGFRβ fusion in pediatric T-cell acute lymphoblastic leukemia." Haematologica  In: , Vol. 103, No. 2, 31.01.2018, p. e87-e91.
  • "Gain-of-function mutations in granulocyte colony–stimulating factor receptor (CSF3R) reveal distinct mechanisms of CSF3R activation." Journal of Biological Chemistry In: , Vol. 293, No. 19, 01.01.2018, p. 7387-7396.
  • "DNA distress creates lethal opportunity in MPN." Blood In: , Vol. 130, No. 26, 28.12.2017, p. 2814-2816.
  • "Characterization of the leukemogenic potential of distal cytoplasmic CSF3R truncation and missense mutations." Leukemia In: , Vol. 31, No. 12, 01.12.2017, p. 2752-2760.
  • "Super-enhancers promote transcriptional dysregulation in nasopharyngeal carcinoma." Cancer Research  In: , Vol. 77, No. 23, 01.12.2017, p. 6614-6626.
  • "Kinase profiling of liposarcomas using RNAi and drug screening assays identified druggable targets." Journal of Hematology and Oncology  In: , Vol. 10, No. 1, 173, 13.11.2017.
  • "Metabolic reprogramming ensures cancer cell survival despite oncogenic signaling blockade." Genes and Development In: , Vol. 31, No. 20, 15.10.2017, p. 2067-2084.
  • "Recent Progress in Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia." Current Hematologic Malignancy Reports  In: , 06.10.2017, p. 1-10.
  • "Evaluation of safety in biomarker driven multiple agent phase IB trial."   Frontiers of Biostatistical Methods and Applications in Clinical Oncology. Springer Singapore, 2017. p. 53-64.
  • "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.

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