Timothy Ley, M.D.,  The Genome Institute

Dr. Ley is a hematologist, oncologist and cancer biologist. He is an internationally known expert in the pathogenesis of acute myeloid leukemia (AML) and other blood-related disorders. Dr. Ley’s research group was one of the first to focus on the reference sequence of the human genome to systematically identify the mutations responsible for the initiation and progression of cancer, focusing primarily on AML. To better understand the role of these mutations, Dr. Ley and his colleagues have constructed several mouse models of acute promyelocytic leukemia (APL). These mice have many features of the human disease, and have been valuable for understanding the genetic pathways altered in this disease. In addition, Dr. Ley’s laboratory has long been interested in the tools and methods needed to correct single gene defects. They currently are using both genetic approaches and expression profiling to identify the homologous recombination “signature” to improve the efficiency of this process in both embryonic and hematopoietic stem cells.

Dr. Ley is the Lewis T. and Rosalind B. Apple Professor of Oncology in the Department of Medicine, and is chief of the Section of Stem Cell Biology in the Division of Oncology. He is also Director of the Embryonic Stem Cell Core at the Siteman Cancer Center, and Professor of Genetics. Dr. Ley received his B.A. degree from Drake University in 1974, and his M.D. from Washington University School of Medicine in 1978. He did his internship and residency in Medicine at Massachusetts General Hospital, was a Clinical Associate at the National Heart, Lung, and Blood Institute, a Hematology-Oncology Fellow at Washington University Medical Center, and a Senior Investigator at the National Heart, Lung, and Blood Institute before moving to Washington University in 1986.

An extensive list of Dr. Ley's publications is available through the Washington University Divisions of Hematology and Oncology.

Publications

title citation publication date
U2AF1 Mutations alter sequence specificity of pre-mRNA binding and splicing. Leukemia. 2014 Oct 14. doi: 10.1038/leu.2014.303. [Epub ahead of print] 2014-10-14
Age-related mutations associated with clonal hematopoietic expansion and malignancies. Nat Med. 2014 Oct 19. doi: 10.1038/nm.3733. [Epub ahead of print] 2014-10-19
SciClone: Inferring Clonal Architecture and Tracking the Spatial and Temporal Patterns of Tumor Evolution. PLoS Comput Biol. 2014 Aug 7;10(8):e1003665. doi: 10.1371/journal.pcbi.1003665. eCollection 2014. 2014-08-07
The R882H DNMT3A mutation associated with AML dominantly inhibits wild-type DNMT3A by blocking its ability to form active tetramers. Cancer Cell. 2014 Apr 14;25(4):442-54. doi: 10.1016/j.ccr.2014.02.010. Epub 2014 Mar 20 2014-04-14
Functional heterogeneity of genetically defined subclones in acute myeloid leukemia. Cancer Cell. 2014 Mar 17;25(3):379-92. doi: 10.1016/j.ccr.2014.01.031. Epub 2014 Mar 6. 2014-03-17
The DNA double-strand break response is abnormal in myeloblasts from patients with therapy-related acute myeloid leukemia. Leukemia. 2013 Dec 5. doi: 10.1038/leu.2013.368. [Epub ahead of print] 2013-12-05
Genomic landscapes and clonality of de novo AML. N Engl J Med. 2013 Oct 10;369(15):1473. doi: 10.1056/NEJMc1308782. 2013-10-10
Mutational landscape and significance across 12 major cancer types. Nature. 2013 Oct 17;502(7471):333-9. doi: 10.1038/nature12634. 2013-10-17
DGIdb: mining the druggable genome. Nat Methods. 2013 Oct 13. doi: 10.1038/nmeth.2689. [Epub ahead of print] 2013-10-13
The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet. 2013 Sep 26;45(10):1113-20. doi: 10.1038/ng.2764. 2013-09-26
BreakTrans: uncovering the genomic architecture of gene fusions. Genome Biol. 2013 Aug 23;14(8):R87. [Epub ahead of print] 2013-08-23
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. Blood. 2007 Feb 1;109(3):1237-40. Epub 2006 Sep 28. 2007-02-01
Mutational profiling in the human genome. Cold Spring Harb Symp Quant Biol. 2003;68:23-9. 2003-01-01
Genomic and Epigenomic Landscapes of Adult De Novo Acute Myeloid Leukemia. N Engl J Med. 2013 May 1. [Epub ahead of print] 2013-05-01
Clonal diversity of recurrently mutated genes in myelodysplastic syndromes. Leukemia. 2013 Feb 27. doi: 10.1038/leu.2013.58. [Epub ahead of print] 2013-02-27
Genomic impact of transient low-dose decitabine treatment on primary AML cells. Blood. 2013 Jan 7. [Epub ahead of print] 2013-01-07
An Inv(16)(p13.3q24.3)-Encoded CBFA2T3-GLIS2 Fusion Protein Defines an Aggressive Subtype of Pediatric Acute Megakaryoblastic Leukemia. Cancer Cell. 2012 Nov 13;22(5):683-97. doi: 10.1016/j.ccr.2012.10.007. 2012-11-13
Whole-genome analysis informs breast cancer response to aromatase inhibition. Nature. 2012 Jun 10;486(7403):353-60. doi: 10.1038/nature11143. 2012-06-10
The origin and evolution of mutations in acute myeloid leukemia. Cell. 2012 Jul 20;150(2):264-78. 2012-07-20
The pediatric cancer genome project. Nat Genet. 2012 May 29;44(6):619-22. doi: 10.1038/ng.2287. 2012-05-29
BreakFusion: Targeted Assembly-based Identification of Gene Fusions in Whole Transcriptome Paired-end Sequencing Data. Bioinformatics. 2012 May 4. [Epub ahead of print] 2012-05-04
Background Mutations in Parental Cells Account for Most of the Genetic Heterogeneity of Induced Pluripotent Stem Cells. Cell Stem Cell. 2012 Apr 26. [Epub ahead of print] 2012-04-26
Clonal Architecture of Secondary Acute Myeloid Leukemia. N Engl J Med. 2012 Mar 22;366(12):1090-8. doi: 10.1056/NEJMoa1106968. Epub 2012 Mar 14. 2012-03-14
Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature. 2012 Jan 11. doi: 10.1038/nature10738. [Epub ahead of print] 2012-01-11
The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature. 2012 Jan 11;481(7380):157-63. doi: 10.1038/nature10725. 2012-01-11
SomaticSniper: Identification of Somatic Point Mutations in Whole Genome Sequencing Data. Bioinformatics. 2011 Dec 6. [Epub ahead of print] 2011-12-06
Recurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromes. Nat Genet. 2011 Dec 11. doi: 10.1038/ng.1031. [Epub ahead of print] 2011-12-11
PML-RARA can increase hematopoietic self-renewal without causing a myeloproliferative disease in mice. J Clin Invest. 2011 Mar 1. pii: 42953. doi: 10.1172/JCI42953. [Epub ahead of print] 2011-03-01
Identification of a Novel TP53 Cancer Susceptibility Mutation Through Whole-Genome Sequencing of a Patient With Therapy-Related AML JAMA. 2011 Apr 20;305(15):1568-1576. 2011-04-20
Use of Whole-Genome Sequencing to Diagnose a Cryptic Fusion Oncogene JAMA. 2011 Apr 20;305(15):1577-84. 2011-04-20
Sequencing a mouse acute promyelocytic leukemia genome reveals genetic events relevant for disease progression. J Clin Invest. 2011 Mar 23. pii: 45284. doi: 10.1172/JCI45284. [Epub ahead of print] 2011-03-23
Recurrent DNMT3A mutations in patients with myelodysplastic syndromes. Leukemia. 2011 Jul;25(7):1153-8. doi: 10.1038/leu.2011.44. Epub 2011 Mar 18. 2011-03-18
Complete characterization of the microRNAome in a patient with acute myeloid leukemia. Blood. 2010 Dec 9;116(24):5316-26. Epub 2010 Sep 28. 2010-12-09
Next-generation sequencing identifies the natural killer cell microRNA transcriptome. Genome Res. 2010 Nov;20(11):1590-604. Epub 2010 Oct 8. 2010-11-01
DNMT3A Mutations in Acute Myeloid Leukemia N Engl J Med. 2010 Nov 10. 2010-11-10
International network of cancer genome projects. Nature. 2010 Apr 15;464(7291):993-8. 2010-04-15
Next-generation sequencing of cancer genomes: back to the future. Per Med. 2009 Nov 1;6(6):653. 2009-11-01
Genome remodelling in a basal-like breast cancer metastasis and xenograft. Nature. 2010 Apr 15;464(7291):989-90. 2010-04-15
BreakDancer: an algorithm for high-resolution mapping of genomic structural variation. Nat Methods. 2009 Sep;6(9):677-81. Epub 2009 Aug 9. 2009-09-06
Acquired copy number alterations in adult acute myeloid leukemia genomes. Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12950-5. Epub 2009 Jul 27. 2009-08-04
Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med. 2009 Sep 10;361(11):1058-66. Epub 2009 Aug 5. 2009-09-10
DNA sequencing of a cytogenetically normal acute myeloid leukaemia (AML) genome. Nature. 2008 Nov 6;456(7218):66-72. 2008-11-06
Somatic mutations and germline sequence variants in the expressed tyrosine kinase genes of patients with de novo acute myeloid leukemia. Blood. 2008 May 1;111(9):4797-808. Epub 2008 Feb 12. 2008-05-01
Identification of somatic JAK1 mutations in patients with acute myeloid leukemia. Blood. 2008 May 1;111(9):4809-12. Epub 2007 Dec 26. 2008-05-01
Distinct patterns of mutations occurring in de novo AML versus AML arising in the setting of severe congenital neutropenia. Blood. 2007 Sep 1;110(5):1648-55. Epub 2007 May 9. 2007-05-10
Reduced PU.1 expression causes myeloid progenitor expansion and increased leukemia penetrance in mice expressing PML-RARalpha. Proc Natl Acad Sci U S A. 2005 Aug 30;102(35):12513-8. Epub 2005 Aug 19. 2005-08-30
A pilot study of high-throughput, sequence-based mutational profiling of primary human acute myeloid leukemia cell genomes. Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14275-80. Epub 2003 Nov 12. 2003-11-25