Thomas O'Hare

Summary

Affiliation: Oregon Health and Science University
Country: USA

Publications

  1. ncbi request reprint Inhibition of wild-type and mutant Bcr-Abl by AP23464, a potent ATP-based oncogenic protein kinase inhibitor: implications for CML
    Thomas O'Hare
    Howard Hughes Medical Institute, Oregon Health and Science University, L592, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA
    Blood 104:2532-9. 2004
  2. ncbi request reprint In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants
    Thomas O'Hare
    Howard Hughes Medical Institute, Oregon Health and Science University Cancer Institute, Portland 97239, USA
    Cancer Res 65:4500-5. 2005
  3. ncbi request reprint Combined Abl inhibitor therapy for minimizing drug resistance in chronic myeloid leukemia: Src/Abl inhibitors are compatible with imatinib
    Thomas O'Hare
    Howard Hughes Medical Institute, Oregon Health and Science University, Portland 97239, USA
    Clin Cancer Res 11:6987-93. 2005
  4. ncbi request reprint A simple method for determining K(A)s of both low and high affinity IgG antibodies
    T O'Hare
    Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland 97201, USA
    J Immunol Methods 218:161-7. 1998
  5. doi request reprint Targeting the BCR-ABL signaling pathway in therapy-resistant Philadelphia chromosome-positive leukemia
    Thomas O'Hare
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, Oregon, USA
    Clin Cancer Res 17:212-21. 2011
  6. pmc Kinase domain mutants of Bcr-Abl exhibit altered transformation potency, kinase activity, and substrate utilization, irrespective of sensitivity to imatinib
    Ian J Griswold
    Center for Hematologic Malignancies, Oregon Health and Science University, 3181 S W Sam Jackson Park Rd, Portland, OR 97239 3098, USA
    Mol Cell Biol 26:6082-93. 2006
  7. pmc Comparison of imatinib mesylate, dasatinib (BMS-354825), and nilotinib (AMN107) in an N-ethyl-N-nitrosourea (ENU)-based mutagenesis screen: high efficacy of drug combinations
    Heather A Bradeen
    Oregon Health and Science University Cancer Institute, L592, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA
    Blood 108:2332-8. 2006
  8. pmc The ABL switch control inhibitor DCC-2036 is active against the chronic myeloid leukemia mutant BCR-ABLT315I and exhibits a narrow resistance profile
    Christopher A Eide
    Oregon Health and Science University, Knight Cancer Institute, Portland, OR, USA
    Cancer Res 71:3189-95. 2011
  9. ncbi request reprint New Bcr-Abl inhibitors in chronic myeloid leukemia: keeping resistance in check
    Thomas O'Hare
    Oregon Health and Science University Cancer Institute, Howard Hughes Medical Institute, Portland, Oregon 97239, USA
    Expert Opin Investig Drugs 17:865-78. 2008
  10. ncbi request reprint Targeted CML therapy: controlling drug resistance, seeking cure
    Thomas O'Hare
    Howard Hughes Medical Institute, Oregon Health and Science University Cancer Institute, L592, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
    Curr Opin Genet Dev 16:92-9. 2006

Collaborators

Detail Information

Publications33

  1. ncbi request reprint Inhibition of wild-type and mutant Bcr-Abl by AP23464, a potent ATP-based oncogenic protein kinase inhibitor: implications for CML
    Thomas O'Hare
    Howard Hughes Medical Institute, Oregon Health and Science University, L592, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA
    Blood 104:2532-9. 2004
    ..The potency of AP23464 against imatinib mesylate-refractory Bcr-Abl and its distinct binding mode relative to imatinib mesylate warrant further investigation of AP23464 for the treatment of CML...
  2. ncbi request reprint In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants
    Thomas O'Hare
    Howard Hughes Medical Institute, Oregon Health and Science University Cancer Institute, Portland 97239, USA
    Cancer Res 65:4500-5. 2005
    ..Thus, both inhibitors hold promise for treating imatinib-refractory CML...
  3. ncbi request reprint Combined Abl inhibitor therapy for minimizing drug resistance in chronic myeloid leukemia: Src/Abl inhibitors are compatible with imatinib
    Thomas O'Hare
    Howard Hughes Medical Institute, Oregon Health and Science University, Portland 97239, USA
    Clin Cancer Res 11:6987-93. 2005
    ..As combination therapy is frequently used to prevent emergence of resistance, the combination of imatinib with an inhibitor of imatinib-resistant Bcr-Abl mutants (e.g., Src/Abl inhibitors AP23848 and BMS-354825) was investigated...
  4. ncbi request reprint A simple method for determining K(A)s of both low and high affinity IgG antibodies
    T O'Hare
    Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland 97201, USA
    J Immunol Methods 218:161-7. 1998
    ..The K(A) is obtained by Scatchard analysis...
  5. doi request reprint Targeting the BCR-ABL signaling pathway in therapy-resistant Philadelphia chromosome-positive leukemia
    Thomas O'Hare
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, Oregon, USA
    Clin Cancer Res 17:212-21. 2011
    ....
  6. pmc Kinase domain mutants of Bcr-Abl exhibit altered transformation potency, kinase activity, and substrate utilization, irrespective of sensitivity to imatinib
    Ian J Griswold
    Center for Hematologic Malignancies, Oregon Health and Science University, 3181 S W Sam Jackson Park Rd, Portland, OR 97239 3098, USA
    Mol Cell Biol 26:6082-93. 2006
    ..The drug resistance and transformation potency of mutants may determine the outcome of patients on therapy with Abl kinase inhibitors...
  7. pmc Comparison of imatinib mesylate, dasatinib (BMS-354825), and nilotinib (AMN107) in an N-ethyl-N-nitrosourea (ENU)-based mutagenesis screen: high efficacy of drug combinations
    Heather A Bradeen
    Oregon Health and Science University Cancer Institute, L592, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA
    Blood 108:2332-8. 2006
    ..However, sequencing uniformly revealed T315I, consistent with the need for a T315I inhibitor, to completely block resistance...
  8. pmc The ABL switch control inhibitor DCC-2036 is active against the chronic myeloid leukemia mutant BCR-ABLT315I and exhibits a narrow resistance profile
    Christopher A Eide
    Oregon Health and Science University, Knight Cancer Institute, Portland, OR, USA
    Cancer Res 71:3189-95. 2011
    ..Taken together, these findings support continued evaluation of DCC-2036 as an important new agent for treatment-refractory CML...
  9. ncbi request reprint New Bcr-Abl inhibitors in chronic myeloid leukemia: keeping resistance in check
    Thomas O'Hare
    Oregon Health and Science University Cancer Institute, Howard Hughes Medical Institute, Portland, Oregon 97239, USA
    Expert Opin Investig Drugs 17:865-78. 2008
    ..Improved Abl inhibitor therapies will be useful in achieving maximum disease control but a clinical T315I inhibitor remains a high priority...
  10. ncbi request reprint Targeted CML therapy: controlling drug resistance, seeking cure
    Thomas O'Hare
    Howard Hughes Medical Institute, Oregon Health and Science University Cancer Institute, L592, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
    Curr Opin Genet Dev 16:92-9. 2006
    ..Together, these advances are contributing to a high level of disease control, and might ultimately lead to disease eradication...
  11. pmc SGX393 inhibits the CML mutant Bcr-AblT315I and preempts in vitro resistance when combined with nilotinib or dasatinib
    Thomas O'Hare
    Division of Hematology and Medical Oncology, Oregon Health and Science University Cancer Institute, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
    Proc Natl Acad Sci U S A 105:5507-12. 2008
    ..These findings suggest that combination of a T315I inhibitor with the current clinically used inhibitors may be useful for reduction of Bcr-Abl mutants in Philadelphia chromosome-positive leukemia...
  12. ncbi request reprint Activating alleles of JAK3 in acute megakaryoblastic leukemia
    Denise K Walters
    Howard Hughes Medical Institute, Portland, Oregon 97239, USA
    Cancer Cell 10:65-75. 2006
    ..These findings illustrate the biological importance of gain-of-function JAK3 mutations in leukemogenesis and demonstrate the utility of proteomic approaches to identifying clinically relevant mutations...
  13. pmc A BCR-ABL mutant lacking direct binding sites for the GRB2, CBL and CRKL adapter proteins fails to induce leukemia in mice
    Kara J Johnson
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, Oregon, United States of America
    PLoS ONE 4:e7439. 2009
    ..Our data suggest that inhibition of BCR-ABL-induced leukemia by disrupting protein interactions could be possible, but would require blocking of multiple sites...
  14. pmc AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance
    Thomas O'Hare
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, OR 97239, USA
    Cancer Cell 16:401-12. 2009
    ..Our work supports clinical evaluation of AP24534 as a pan-BCR-ABL inhibitor for treatment of CML...
  15. pmc KIT signaling governs differential sensitivity of mature and primitive CML progenitors to tyrosine kinase inhibitors
    Amie S Corbin
    Authors Affiliations OHSU Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon Howard Hughes Medical Institute, Chevy Chase, Maryland Huntsman Cancer Institute Division of Hematology and Hematologic Malignancies, The University of Utah, Salt Lake City, Utah Novartis Institutes for BioMedical Research, Basel, Switzerland and Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas
    Cancer Res 73:5775-86. 2013
    ....
  16. pmc The BCR-ABL35INS insertion/truncation mutant is kinase-inactive and does not contribute to tyrosine kinase inhibitor resistance in chronic myeloid leukemia
    Thomas O'Hare
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, USA
    Blood 118:5250-4. 2011
    ....
  17. pmc Acute dasatinib exposure commits Bcr-Abl-dependent cells to apoptosis
    Jennifer L Snead
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, OR 97239, USA
    Blood 114:3459-63. 2009
    ..Furthermore, they challenge the widely held notion that continuous target inhibition is required for optimal efficacy of kinase inhibitors...
  18. pmc RNAi screening of the tyrosine kinome identifies therapeutic targets in acute myeloid leukemia
    Jeffrey W Tyner
    Division of Hematology and Medical Oncology, Oregon Health and Science University Cancer Institute, Portland, USA
    Blood 111:2238-45. 2008
    ..This technique, with additional development, might eventually offer the potential to match specific therapies with individual patients based on a functional assay...
  19. pmc RNAi screen for rapid therapeutic target identification in leukemia patients
    Jeffrey W Tyner
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, OR 97239, USA
    Proc Natl Acad Sci U S A 106:8695-700. 2009
    ..Combination of this technique with whole-genome sequencing will represent an ideal tool for oncogenic target identification such that specific therapies can be matched with individual patients...
  20. pmc Absence of SKP2 expression attenuates BCR-ABL-induced myeloproliferative disease
    Anupriya Agarwal
    Division of Hematology and Oncology, Oregon Health and Science University Cancer Institute, Portland, OR 97239, USA
    Blood 112:1960-70. 2008
    ..Hence, stabilization of p27 by inhibiting its recognition by SCF(SKP2) may be therapeutically useful...
  21. ncbi request reprint AMN107: tightening the grip of imatinib
    Thomas O'Hare
    Howard Hughes Medical Institute, Oregon Health and Science University Cancer Institute, Portland, Oregon, 97239, USA
    Cancer Cell 7:117-9. 2005
    ..The implications of these results, and the potential role this and other novel ABL inhibitors may have in treating patients with CML, are discussed...
  22. pmc TNF╬▒ facilitates clonal expansion of JAK2V617F positive cells in myeloproliferative neoplasms
    Angela G Fleischman
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, OR, USA
    Blood 118:6392-8. 2011
    ....
  23. doi request reprint New strategies for the first-line treatment of chronic myeloid leukemia: can resistance be avoided?
    Jennifer L Snead
    Oregon Health and Science University Cancer Institute, Portland, OR, USA
    Clin Lymphoma Myeloma 8:S107-17. 2008
    ..Herein, we review current and emerging paradigms for using Abl kinase inhibitors to achieve maximal disease control and strategies to eradicate disease by targeting leukemic stem cells...
  24. ncbi request reprint Recovering antibody secretion using a hapten ligand as a chemical chaperone
    G D Wiens
    Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon 97201 3098, USA
    J Biol Chem 276:40933-9. 2001
    ....
  25. ncbi request reprint Mutation of a single conserved residue in VH complementarity-determining region 2 results in a severe Ig secretion defect
    G D Wiens
    Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland, OR 97201, USA
    J Immunol 167:2179-86. 2001
    ..These results represent the first demonstration that single somatic mutations in V(H) residues can impair Ig secretion and suggest one reason for the conservation of Ile51 in so many Ig VH...
  26. ncbi request reprint Harmful somatic mutations: lessons from the dark side
    G D Wiens
    Department of Molecular Microbiology, Oregon Health Sciences University, Portland 97201, USA
    Immunol Rev 162:197-209. 1998
    ..Here we review our recent findings in understanding the structural and functional consequences of V-region mutation...
  27. pmc Kinase pathway dependence in primary human leukemias determined by rapid inhibitor screening
    Jeffrey W Tyner
    Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, OR 97239, USA
    Cancer Res 73:285-96. 2013
    ..Taken together, our results suggested that drug target scores derived from a comprehensive kinase inhibitor panel could predict pathway dependence in cancer cells while simultaneously identifying potential therapeutic options...
  28. ncbi request reprint Clonal diversity, somatic mutation, and immune memory to phosphocholine-keyhole limpet hemocyanin
    M P Stenzel-Poore
    Department of Microbiology and Immunology, Oregon Health Sciences University, Portland 97201
    J Immunol 143:4123-33. 1989
    ..From these findings it appears that somatic mutation plays a major role in anti-PC-keyhole limpet hemocyanin memory development because all 14 antibodies displayed changes from germ-line sequences...
  29. ncbi request reprint Single particle quantum dot imaging achieves ultrasensitive detection capabilities for Western immunoblot analysis
    Benjamin Scholl
    Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR 97239, USA
    ACS Nano 3:1318-28. 2009
    ....
  30. ncbi request reprint Association of human transferrin receptor with GABARAP
    Frank Green
    Department of Cell and Developmental Biology, L215, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97201 3098, USA
    FEBS Lett 518:101-6. 2002
    ..Our results show that GABARAP plays a more general role outside the confines of neuronal cells and GABA(A) receptors...
  31. ncbi request reprint Natural auto- and polyreactive antibodies differing from antigen-induced antibodies in the H chain CDR3
    C Chen
    Department of Microbiology and Immunology, Oregon Health Sciences University, Portland 97201
    J Immunol 147:2359-67. 1991
    ..The results suggest that CDR3 of the H chain may play a critical role in distinguishing poly- from monospecific combining sites in natural and Ag-induced antibodies...
  32. ncbi request reprint A genetic model of stress displays decreased lymphocytes and impaired antibody responses without altered susceptibility to Streptococcus pneumoniae
    S E Murray
    Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland, OR 97201, USA
    J Immunol 167:691-8. 2001
    ..This increase in number of neutrophils may compensate for the depressed IgG response, allowing adequate host defense during chronic stress...
  33. ncbi request reprint Cutting edge: proteasome involvement in the degradation of unassembled Ig light chains
    T O'Hare
    Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland 97201, USA
    J Immunol 163:11-4. 1999
    ..To our knowledge, we provide the first direct evidence supporting a new paradigm for removal of nonsecreted Ig L chains via dislocation to cytosolic proteasomes...