Timothy J Ley

Summary

Affiliation: Washington University School of Medicine
Country: USA

Publications

  1. pmc A pilot study of high-throughput, sequence-based mutational profiling of primary human acute myeloid leukemia cell genomes
    Timothy J Ley
    Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 100:14275-80. 2003
  2. pmc Neutrophil elastase is important for PML-retinoic acid receptor alpha activities in early myeloid cells
    Andrew A Lane
    Departments of Medicine and Genetics, Division of Oncology, Siteman Cancer Center, Washington University, 660 S Euclid Ave, Campus Box 8007, St Louis, MO 63110 1093, USA
    Mol Cell Biol 25:23-33. 2005
  3. ncbi request reprint The physician-scientist career pipeline in 2005: build it, and they will come
    Timothy J Ley
    Section of Stem Cell Biology, Division of Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO 63110, USA
    JAMA 294:1343-51. 2005
  4. ncbi request reprint Retrospective: Stanley Joel Korsmeyer (1950-2005)
    Timothy J Ley
    Departments of Medicine and Genetics, Washington University, St Louis, MO 63110, USA
    Science 308:803-4. 2005
  5. pmc Differential expression of granzyme B and C in murine cytotoxic lymphocytes
    Sheng F Cai
    Department of Internal Medicine, Division of Oncology, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO 63110, USA
    J Immunol 182:6287-97. 2009
  6. pmc Expression and function of PML-RARA in the hematopoietic progenitor cells of Ctsg-PML-RARA mice
    Lukas D Wartman
    Section of Stem Cell Biology, Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, Missouri, USA
    PLoS ONE 7:e46529. 2012
  7. ncbi request reprint Neutrophil elastase cleaves PML-RARalpha and is important for the development of acute promyelocytic leukemia in mice
    Andrew A Lane
    Division of Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO 63110, USA
    Cell 115:305-18. 2003
  8. pmc DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome
    Timothy J Ley
    Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63108, USA
    Nature 456:66-72. 2008
  9. pmc Reduced PU.1 expression causes myeloid progenitor expansion and increased leukemia penetrance in mice expressing PML-RARalpha
    Matthew J Walter
    Department of Medicine, Division of Oncology, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 102:12513-8. 2005
  10. pmc Clonal architecture of secondary acute myeloid leukemia
    Matthew J Walter
    Department of Internal Medicine, Division of Oncology, Washington University School of Medicine, St Louis, MO 63110, USA
    N Engl J Med 366:1090-8. 2012

Research Grants

  1. REGULATION OF FETAL AND ADULT HUMAN HEMOGLOBIN PROD
    TIMOTHY LEY; Fiscal Year: 2007
  2. Genomics of Acute Myelogenous Leukemia
    TIMOTHY LEY; Fiscal Year: 2007

Detail Information

Publications71

  1. pmc A pilot study of high-throughput, sequence-based mutational profiling of primary human acute myeloid leukemia cell genomes
    Timothy J Ley
    Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 100:14275-80. 2003
    ..This strategy represents a viable approach for the detection of potentially relevant, nonrandom mutations in primary human cancer cell genomes...
  2. pmc Neutrophil elastase is important for PML-retinoic acid receptor alpha activities in early myeloid cells
    Andrew A Lane
    Departments of Medicine and Genetics, Division of Oncology, Siteman Cancer Center, Washington University, 660 S Euclid Ave, Campus Box 8007, St Louis, MO 63110 1093, USA
    Mol Cell Biol 25:23-33. 2005
    ..To assure physiologic relevance, PML-RARalpha functions should be evaluated in neutrophil elastase-expressing early myeloid cells...
  3. ncbi request reprint The physician-scientist career pipeline in 2005: build it, and they will come
    Timothy J Ley
    Section of Stem Cell Biology, Division of Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO 63110, USA
    JAMA 294:1343-51. 2005
    ..A variety of factors were thought to contribute to this problem, including increasing indebtedness of medical school graduates caused by rapidly rising medical school tuition costs...
  4. ncbi request reprint Retrospective: Stanley Joel Korsmeyer (1950-2005)
    Timothy J Ley
    Departments of Medicine and Genetics, Washington University, St Louis, MO 63110, USA
    Science 308:803-4. 2005
  5. pmc Differential expression of granzyme B and C in murine cytotoxic lymphocytes
    Sheng F Cai
    Department of Internal Medicine, Division of Oncology, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO 63110, USA
    J Immunol 182:6287-97. 2009
    ..Taken together, these findings suggest that granzyme C is activated with persistent antigenic stimulation, providing nonredundant backup protection for the host when granzyme B fails...
  6. pmc Expression and function of PML-RARA in the hematopoietic progenitor cells of Ctsg-PML-RARA mice
    Lukas D Wartman
    Section of Stem Cell Biology, Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, Missouri, USA
    PLoS ONE 7:e46529. 2012
    ....
  7. ncbi request reprint Neutrophil elastase cleaves PML-RARalpha and is important for the development of acute promyelocytic leukemia in mice
    Andrew A Lane
    Division of Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO 63110, USA
    Cell 115:305-18. 2003
    ..Since NE is maximally produced in promyelocytes, this protease may play a role in APL pathogenesis by facilitating the leukemogenic potential of PML-RARalpha...
  8. pmc DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome
    Timothy J Ley
    Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63108, USA
    Nature 456:66-72. 2008
    ..Our study establishes whole-genome sequencing as an unbiased method for discovering cancer-initiating mutations in previously unidentified genes that may respond to targeted therapies...
  9. pmc Reduced PU.1 expression causes myeloid progenitor expansion and increased leukemia penetrance in mice expressing PML-RARalpha
    Matthew J Walter
    Department of Medicine, Division of Oncology, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 102:12513-8. 2005
    ..1 through a deletional mechanism, plus down-regulation of the residual allele caused by PR expression, may synergize to expand the pool of myeloid progenitors that are susceptible to transformation, increasing the penetrance of APL...
  10. pmc Clonal architecture of secondary acute myeloid leukemia
    Matthew J Walter
    Department of Internal Medicine, Division of Oncology, Washington University School of Medicine, St Louis, MO 63110, USA
    N Engl J Med 366:1090-8. 2012
    ..The genetic changes that underlie progression from the myelodysplastic syndromes to secondary AML are not well understood...
  11. ncbi request reprint Granzyme B and the downstream granzymes C and/or F are important for cytotoxic lymphocyte functions
    Paula A Revell
    Division of Oncology, Department of Internal Medicine, Siteman Cancer Center, Washington University School of Medicine, St Louis Children s Hospital, St Louis, MO 63110, USA
    J Immunol 174:2124-31. 2005
    ..These results suggest that the retained PGK-neo cassette in the GzmB gene causes a knockdown of GzmC and F expression, and also suggest that these granzymes are relevant for the function of cytotoxic lymphocytes in vitro and in vivo...
  12. pmc Acquired copy number alterations in adult acute myeloid leukemia genomes
    Matthew J Walter
    Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 106:12950-5. 2009
    ....
  13. ncbi request reprint Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance
    Xuefang Cao
    Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Immunity 27:635-46. 2007
    ..Granzyme B and perforin are therefore relevant for Treg cell-mediated suppression of tumor clearance in vivo...
  14. pmc Expression profiling of murine acute promyelocytic leukemia cells reveals multiple model-dependent progression signatures
    Matthew J Walter
    Division of Oncology, Section of Stem Cell Biology, Campus Box 8007, 660 South Euclid Ave, St Louis, MO 63110 1093, USA
    Mol Cell Biol 24:10882-93. 2004
    ..The two models exhibited distinct gene expression profiles, suggesting that the dominant molecular signatures of murine acute promyelocytic leukemia can be influenced by several independent progression events...
  15. ncbi request reprint High-penetrance mouse model of acute promyelocytic leukemia with very low levels of PML-RARalpha expression
    Peter Westervelt
    Washington University, Division of Oncology, 660 S Euclid Ave, Campus Box 8007, St Louis, MO 63110 1093, USA
    Blood 102:1857-65. 2003
    ..Although the explanation for this result is not yet clear, one hypothesis suggests that very low levels of PML-RARalpha expression in early myeloid cells may be optimal for the development of APL in mice...
  16. pmc The origin and evolution of mutations in acute myeloid leukemia
    John S Welch
    Department of Medicine, Washington University, St Louis, MO 63110, USA
    Cell 150:264-78. 2012
    ..Cells from the founding clone can acquire additional cooperating mutations, yielding subclones that can contribute to disease progression and/or relapse...
  17. pmc Genome remodelling in a basal-like breast cancer metastasis and xenograft
    Li Ding
    The Genome Center at Washington University, St Louis, Missouri 63108, USA
    Nature 464:999-1005. 2010
    ..The differential mutation frequencies and structural variation patterns in metastasis and xenograft compared with the primary tumour indicate that secondary tumours may arise from a minority of cells within the primary tumour...
  18. pmc Commonly dysregulated genes in murine APL cells
    Wenlin Yuan
    Department of Medicine, Siteman Cancer Center, and Department of Pathology and Immunology, Washington University, St Louis, MO 63110, USA
    Blood 109:961-70. 2007
    ..These studies suggest that the genetic events that lead to APL progression may converge on common pathways that are important for leukemia pathogenesis...
  19. pmc Latent herpesvirus infection arms NK cells
    Douglas W White
    Division of Rheumatology, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Blood 115:4377-83. 2010
    ..Thus, the immune environment created by latent herpesvirus infection provides a mechanism whereby host NK-cell function is enhanced in vivo...
  20. pmc Granzyme B is not required for regulatory T cell-mediated suppression of graft-versus-host disease
    Sheng F Cai
    Section of Stem Cell Biology, Division of Oncology, Departments of Internal Medicine and Genetics, Washington University School of Medicine, St Louis, MO, USA
    Blood 115:1669-77. 2010
    ..Taken together, these findings suggest that targeting specific T(reg) cell-suppressive mechanisms, such as granzyme B, may be therapeutically beneficial for segregating GVHD and graft-versus-tumor immune responses...
  21. pmc A protease-resistant PML-RAR{alpha} has increased leukemogenic potential in a murine model of acute promyelocytic leukemia
    Geoffrey L Uy
    Section of Stem Cell Biology, Division of Oncology, Washington University School of Medicine, 660 S Euclid Avenue, St Louis, MO 63110, USA
    Blood 116:3604-10. 2010
    ..Together, these effects appear to increase the leukemogenicity of NE-resistant PR, contrary to our previous prediction. We conclude that NE deficiency may reduce APL penetrance via indirect mechanisms that are still NE dependent...
  22. pmc SomaticSniper: identification of somatic point mutations in whole genome sequencing data
    David E Larson
    The Genome Institute, Washington University, St Louis, MO 63108, USA
    Bioinformatics 28:311-7. 2012
    ..Despite this fact, there remains a dearth of available software tools designed to compare sequences in pairs of samples and identify sites that are likely to be unique to one sample...
  23. pmc Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing
    Li Ding
    The Genome Institute, Washington University, St Louis, Missouri 63108, USA
    Nature 481:506-10. 2012
    ..These data demonstrate that AML relapse is associated with the addition of new mutations and clonal evolution, which is shaped, in part, by the chemotherapy that the patients receive to establish and maintain remissions...
  24. pmc Expression of a bcr-1 isoform of RARalpha-PML does not affect the penetrance of acute promyelocytic leukemia or the acquisition of an interstitial deletion on mouse chromosome 2
    Matthew J Walter
    Department of Medicine, Division of Oncology, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO 63110 1093, USA
    Blood 109:1237-40. 2007
    ..38-compared with 11 of 11 for mice coexpressing PML-RARalpha and bcr-3 RARalpha-PML). The bcr-1 and bcr-3 isoforms of RARalpha-PML, therefore, have different biological activities that may be relevant for the pathogenesis of murine APL...
  25. pmc Somatic mutations and germline sequence variants in the expressed tyrosine kinase genes of patients with de novo acute myeloid leukemia
    Michael H Tomasson
    Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Blood 111:4797-808. 2008
    ..Additional studies will be required to define the roles that these somatic and germline TK gene variants play in AML pathogenesis...
  26. pmc DNMT3A mutations in acute myeloid leukemia
    Timothy J Ley
    Department of Genetics, Genome Center, Washington University, St Louis, MO 63110, USA
    N Engl J Med 363:2424-33. 2010
    ..The genetic alterations responsible for an adverse outcome in most patients with acute myeloid leukemia (AML) are unknown...
  27. pmc Use of whole-genome sequencing to diagnose a cryptic fusion oncogene
    John S Welch
    Department of Medicine, Washington University, St Louis, Missouri, USA
    JAMA 305:1577-84. 2011
    ..Whole-genome sequencing is becoming increasingly available for research purposes, but it has not yet been routinely used for clinical diagnosis...
  28. pmc Background mutations in parental cells account for most of the genetic heterogeneity of induced pluripotent stem cells
    Margaret A Young
    Department of Internal Medicine, Division of Oncology, Section of Stem Cell Biology, Washington University, St Louis, MO 63110, USA
    Cell Stem Cell 10:570-82. 2012
    ..These findings have implications for the development and therapeutic use of cells that are reprogrammed by any method...
  29. pmc Quantitative trait loci associated with susceptibility to therapy-related acute murine promyelocytic leukemia in hCG-PML/RARA transgenic mice
    Ryan K Funk
    Department of Internal Medicine, Division of Oncology, Stem Cell Biology Section, Washington University School of Medicine, St Louis, MO 63110, USA
    Blood 112:1434-42. 2008
    ..Improved understanding of genetic risk factors should lead to tailored treatment regimens that reduce risk for patients predisposed to t-AML...
  30. pmc Next-generation sequencing identifies the natural killer cell microRNA transcriptome
    Todd A Fehniger
    Department of Medicine, Division of Oncology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Genome Res 20:1590-604. 2010
    ..Thus, the sequenced NK cell miRNA transcriptome provides a valuable framework for further elucidation of miRNA expression and function in NK cell biology...
  31. pmc Rara haploinsufficiency modestly influences the phenotype of acute promyelocytic leukemia in mice
    John S Welch
    Section of Stem Cell Biology, Division of Oncology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Blood 117:2460-8. 2011
    ..These data show that Rara haploinsufficiency (like Pml haploinsufficiency and RARA-PML) can cooperate with PML-RARA to influence the pathogenesis of APL in mice, but that PML-RARA is the t(15;17) disease-initiating mutation...
  32. pmc wuHMM: a robust algorithm to detect DNA copy number variation using long oligonucleotide microarray data
    Patrick Cahan
    Department of Internal Medicine and Department of Genetics, Division of Oncology, Stem Cell Biology Section, Washington University, St Louis, MO, USA
    Nucleic Acids Res 36:e41. 2008
    ..At a FPR of <10%, the algorithm can detect CNVs with five probes on the 385K platform and three on the 2.1M and 3.1M platforms, resulting in effective resolutions of 24 kb, 2-5 kb and 1 kb, respectively...
  33. ncbi request reprint Acquisition of murine NK cell cytotoxicity requires the translation of a pre-existing pool of granzyme B and perforin mRNAs
    Todd A Fehniger
    Division of Oncology, Department of Internal Medicine, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO 63110, USA
    Immunity 26:798-811. 2007
    ..These data suggest that resting murine NK cells are minimally cytotoxic because of a block in perforin and granzyme B mRNA translation that is released by NK cell activation...
  34. ncbi request reprint Human T regulatory cells can use the perforin pathway to cause autologous target cell death
    William J Grossman
    Department of Pediatrics, Division of Hematology Oncology, St Louis Children s Hospital, St Louis, MO 63110, USA
    Immunity 21:589-601. 2004
    ..This cytotoxicity is dependent on CD18 adhesive interactions but is independent of Fas/FasL. Our findings suggest that the perforin/granzyme pathway is one of the mechanisms that Treg cells can use to control immune responses...
  35. pmc Recurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromes
    Timothy A Graubert
    Department of Internal Medicine, Division of Oncology, Washington University, St Louis, Missouri, USA
    Nat Genet 44:53-7. 2012
    ..Mutant U2AF1 promotes enhanced splicing and exon skipping in reporter assays in vitro. This previously unidentified, recurrent mutation in U2AF1 implicates altered pre-mRNA splicing as a potential mechanism for MDS pathogenesis...
  36. pmc Sequencing a mouse acute promyelocytic leukemia genome reveals genetic events relevant for disease progression
    Lukas D Wartman
    Department of Internal Medicine, Division of Oncology, Stem Cell Biology Section, Washington University School of Medicine, Siteman Cancer Center, St Louis, Missouri, USA
    J Clin Invest 121:1445-55. 2011
    ..In conclusion, whole genome sequencing of mouse cancer genomes can provide an unbiased and comprehensive approach for discovering functionally relevant mutations that are also present in human leukemias...
  37. pmc Mcl1 haploinsufficiency protects mice from Myc-induced acute myeloid leukemia
    Zhifu Xiang
    Department of Medicine, Division of Oncology, Siteman Cancer Center, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Clin Invest 120:2109-18. 2010
    ..Together, these data demonstrate a critical and dose-dependent role for Mcl1 in AML pathogenesis in mice and suggest that MCL1 may be a promising therapeutic target in patients with de novo AML...
  38. ncbi request reprint Murine acute promyelocytic leukemia cells can be recognized and cleared in vivo by adaptive immune mechanisms
    Jessica L Pollock
    Division of Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO 63110, USA
    Haematologica 90:1042-9. 2005
    ..In this study, we tested whether transgenic murine acute promyelocytic leukemia (APL) cells can be recognized and cleared by adaptive immune responses and/or vaccination strategies...
  39. pmc Chemosensitization of acute myeloid leukemia (AML) following mobilization by the CXCR4 antagonist AMD3100
    Bruno Nervi
    Division of Oncology, Washington University School of Medicine, St Louis, MO 63110, USA
    Blood 113:6206-14. 2009
    ..These studies provide a proof-of-principle for directing therapy to the critical tethers that promote AML-niche interactions...
  40. ncbi request reprint Hop cleavage and function in granzyme B-induced apoptosis
    Andrew J Bredemeyer
    Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 281:37130-41. 2006
    ..Although it is possible that Hop may be cleaved by GzmB as an "innocent bystander" during the induction of apoptosis, it may also act to facilitate apoptosis in concert with other GzmB substrates...
  41. pmc High throughput digital quantification of mRNA abundance in primary human acute myeloid leukemia samples
    Jacqueline E Payton
    Department of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University Medical School, St Louis, Missouri 63110, USA
    J Clin Invest 119:1714-26. 2009
    ....
  42. pmc Recurring mutations found by sequencing an acute myeloid leukemia genome
    Elaine R Mardis
    Department of Genetics, Washington University, St Louis, MO 63110, USA
    N Engl J Med 361:1058-66. 2009
    ..The full complement of DNA mutations that are responsible for the pathogenesis of acute myeloid leukemia (AML) is not yet known...
  43. pmc DGIdb: mining the druggable genome
    Malachi Griffith
    1 The Genome Institute, Washington University School of Medicine, St Louis, Missouri, USA 2 Department of Genetics, Washington University School of Medicine, St Louis, Missouri, USA 3
    Nat Methods 10:1209-10. 2013
    ..It provides an interface for searching lists of genes against a compendium of drug-gene interactions and potentially 'druggable' genes. DGIdb can be accessed at http://dgidb.org/. ..
  44. pmc Functional heterogeneity of genetically defined subclones in acute myeloid leukemia
    Jeffery M Klco
    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA
    Cancer Cell 25:379-92. 2014
    ..These data demonstrate the importance of integrating genetic and functional data in studies of primary cancer samples, both in xenograft models and in patients. ..
  45. pmc Computational identification of the normal and perturbed genetic networks involved in myeloid differentiation and acute promyelocytic leukemia
    Li Wei Chang
    Department of Biomedical Engineering, Washington University, St Louis, MO 63130, USA
    Genome Biol 9:R38. 2008
    ..We propose an integrated approach for mammalian genetic network construction by combining the analysis of gene expression profiling data and the identification of TF binding sites...
  46. pmc PML-RARA can increase hematopoietic self-renewal without causing a myeloproliferative disease in mice
    John S Welch
    Section of Stem Cell Biology, Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63119, USA
    J Clin Invest 121:1636-45. 2011
    ..This mouse model provides a platform for more accurately dissecting the early events in APL pathogenesis...
  47. pmc Cold shock domain family members YB-1 and MSY4 share essential functions during murine embryogenesis
    Zhi Hong Lu
    Division of Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO 63110 1093, USA
    Mol Cell Biol 26:8410-7. 2006
    ..5 to E11.5) than YB-1-deficient embryos, suggesting that MSY4 indeed shares critical cellular functions with YB-1 in the embryonic tissues where they are coexpressed...
  48. pmc Identification of somatic JAK1 mutations in patients with acute myeloid leukemia
    Zhifu Xiang
    Department of Medicine, Washington University School of Medicine, St Louis, St Louis, MO 63110, USA
    Blood 111:4809-12. 2008
    ..This is the first report to demonstrate somatic JAK1 mutations in AML and suggests that JAK1 mutations may function as disease-modifying mutations in AML pathogenesis...
  49. pmc The R882H DNMT3A mutation associated with AML dominantly inhibits wild-type DNMT3A by blocking its ability to form active tetramers
    David A Russler-Germain
    Section of Stem Cell Biology, Division of Oncology, Department of Medicine, Washington University, St Louis, MO 63110, USA
    Cancer Cell 25:442-54. 2014
    ..AML cells with the R882H mutation have severely reduced de novo methyltransferase activity and focal hypomethylation at specific CpGs throughout AML cell genomes. ..
  50. ncbi request reprint Clonal architecture of secondary acute myeloid leukemia defined by single-cell sequencing
    Andrew E O Hughes
    Center for Genome Sciences and Systems Biology, Washington University, St Louis, Missouri, United States of America
    PLoS Genet 10:e1004462. 2014
    ....
  51. pmc Whole-genome analysis informs breast cancer response to aromatase inhibition
    Matthew J Ellis
    Department of Internal Medicine, Division of Oncology, Washington University, St Louis, Missouri 63110, USA
    Nature 486:353-60. 2012
    ..Prospective clinical trials based on these findings will require comprehensive genome sequencing...
  52. pmc Adaptive immunity cooperates with liposomal all-trans-retinoic acid (ATRA) to facilitate long-term molecular remissions in mice with acute promyelocytic leukemia
    Peter Westervelt
    Division of Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8007, St Louis, MO 63110 1093, USA
    Proc Natl Acad Sci U S A 99:9468-73. 2002
    ....
  53. pmc Identification of a novel TP53 cancer susceptibility mutation through whole-genome sequencing of a patient with therapy-related AML
    Daniel C Link
    Department of Medicine, Siteman Cancer Center, Washington University, St Louis, Missouri, USA
    JAMA 305:1568-76. 2011
    ..However, in many cases of suspected cancer susceptibility, the family history is unclear and genetic testing of common cancer susceptibility genes is unrevealing...
  54. ncbi request reprint Use of protease proteomics to discover granzyme B substrates
    Andrew J Bredemeyer
    Division of Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO 63110, USA
    Immunol Res 32:143-53. 2005
    ..This approach may serve as an important discovery tool for other immunologic proteases...
  55. pmc Distinct patterns of mutations occurring in de novo AML versus AML arising in the setting of severe congenital neutropenia
    Daniel C Link
    Division of Oncology, Department of Medicine, Washington University, St Louis, MO 63110, USA
    Blood 110:1648-55. 2007
    ..These data support the hypothesis that mutations of CSF3R may provide the "activated tyrosine kinase signal" that is thought to be important for leukemogenesis...
  56. pmc Complete characterization of the microRNAome in a patient with acute myeloid leukemia
    Giridharan Ramsingh
    Deparment of Medicine, Washington University School of Medicine, St Louis, MO, USA
    Blood 116:5316-26. 2010
    ....
  57. pmc Granzymes and caspase 3 play important roles in control of gammaherpesvirus latency
    Joy Loh
    Dept of Pathology and Immunology, Washington University School of Medicine, 660 S Euclid, Box 8118, St Louis, MO 63110, USA
    J Virol 78:12519-28. 2004
    ..The requirement for specific granzymes differs for early versus late forms of latent infection. These data indicate that different granzymes play important and distinct roles in regulating latent gammaherpesvirus infection...
  58. ncbi request reprint Removing career obstacles for young physician-scientists -- loan-repayment programs
    Timothy J Ley
    Washington University School of Medicine, St Louis, MO 63110 1092, USA
    N Engl J Med 346:368-72. 2002
  59. pmc Oncogenic K-ras cooperates with PML-RAR alpha to induce an acute promyelocytic leukemia-like disease
    Iris T Chan
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
    Blood 108:1708-15. 2006
    ....
  60. pmc A high-resolution map of segmental DNA copy number variation in the mouse genome
    Timothy A Graubert
    Department of Medicine, Division of Oncology, Stem Cell Biology Section, Washington University, St Louis, Missouri, United States of America
    PLoS Genet 3:e3. 2007
    ..Annotation of CNVs in the mouse genome combined with sequence-based analysis provides an important resource that will help define the genetic basis of complex traits...
  61. ncbi request reprint Differential expression of granzymes A and B in human cytotoxic lymphocyte subsets and T regulatory cells
    William J Grossman
    Department of Pediatrics, Division of Hematology Oncology, St Louis Children s Hospital, St Louis, MO, USA
    Blood 104:2840-8. 2004
    ..Our results demonstrate discordant expression of granzymes A and B in human lymphocyte subsets and T regulatory cells, which suggests that different granzymes may play unique roles in immune system responses and regulation...
  62. pmc BreakDancer: an algorithm for high-resolution mapping of genomic structural variation
    Ken Chen
    The Genome Center, Washington University School of Medicine, St Louis, Missouri, USA
    Nat Methods 6:677-81. 2009
    ..BreakDancer sensitively and accurately detected indels ranging from 10 base pairs to 1 megabase pair that are difficult to detect via a single conventional approach...
  63. ncbi request reprint Lymphocyte-mediated cytotoxicity
    John H Russell
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Annu Rev Immunol 20:323-70. 2002
    ..host disease, but oversuppression of these pathways may also lead to increased viral susceptibility and/or decreased tumor cell killing...
  64. pmc YB-1 is important for late-stage embryonic development, optimal cellular stress responses, and the prevention of premature senescence
    Zhi Hong Lu
    Division of Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Mol Cell Biol 25:4625-37. 2005
    ..These data suggest that YB-1 normally represses the transcription of CDK inhibitors, making it an important component of the cellular stress response signaling pathway...
  65. pmc A proteomic approach for the discovery of protease substrates
    Andrew J Bredemeyer
    Department of Medicine, Division of Oncology, Siteman Cancer Center and Proteomics Center, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 101:11785-90. 2004
    ..quot;Protease proteomics" may therefore represent an important tool for the discovery of the native substrates of a variety of proteases...
  66. ncbi request reprint Papillon-Lefèvre syndrome: correlating the molecular, cellular, and clinical consequences of cathepsin C/dipeptidyl peptidase I deficiency in humans
    Christine T N Pham
    Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA
    J Immunol 173:7277-81. 2004
    ....
  67. ncbi request reprint 1998 ASCI Presidential Address
    Timothy J Ley
    Washington University School of Medicine, St Louis, Missouri, USA
    J Clin Invest 112:S9-11. 2003
  68. ncbi request reprint The orphan granzymes of humans and mice
    William J Grossman
    Department of Pediatrics, Hale Irwin Center for Pediatric Oncology, 1 St Louis Children s Hospital, St Louis, MO 63110, USA
    Curr Opin Immunol 15:544-52. 2003
    ..Although the functions of these orphan granzymes have yet to be fully established, initial data suggests their importance in both immune and nonimmune cells...
  69. ncbi request reprint Cell death induced by granzyme C
    Hillary Johnson
    Division of Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO 63110, USA
    Blood 101:3093-101. 2003
    ..These results suggest that granzyme C rapidly induces target cell death by attacking nuclear and mitochondrial targets and that these targets are distinct from those used by granzyme B to cause classical apoptosis...
  70. pmc PML/RARalpha and FLT3-ITD induce an APL-like disease in a mouse model
    Louise M Kelly
    Division of Hematology Oncology, Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:8283-8. 2002
    ..The leukemia is transplantable to secondary recipients and is ATRA responsive. These observations document cooperation between PML/RARalpha and FLT3-ITD in development of the murine APL phenotype...
  71. ncbi request reprint Granzymes A and B are not expressed in human neutrophils
    William J Grossman
    Blood 104:906-7; author reply 907-8. 2004

Research Grants3

  1. REGULATION OF FETAL AND ADULT HUMAN HEMOGLOBIN PROD
    TIMOTHY LEY; Fiscal Year: 2007
    ..These studies should allow us to determine whether homologous recombination can be rationally developed as a method for correcting mutations in the P-globin locus within primary hematopoietic progenitor cells. ..
  2. Genomics of Acute Myelogenous Leukemia
    TIMOTHY LEY; Fiscal Year: 2007
    ..abstract_text> ..