Timothy J. Ley, MD

Timothy J. Ley, MD

Lewis T. and Rosalind B. Apple Chair in Oncology

Address:
Division of Oncology
Mail Stop 8007-0057-06
Washington University
660 South Euclid Avenue
St. Louis, MO 63110

629 Southwest Tower (office)
629 Southwest Tower (lab)
Ph: 314-362-8832 (lab)

Admin:
Brittni Canella
brittniblack@wustl.edu

Research Interests
  • Mouse models of acute myeloid leukemias (AML)
  • AML genomics and epigenetics
Research

For many years, the Ley lab has used mouse models of AML to establish key principles of AML pathogenesis. The lab established that the initiating event for Acute Promyelocytic Leukemia is the PML-RARA fusion gene created by the t(15;17) that is found in nearly all patients with this disease. The roles of cooperating mutations and the cellular milieu for APL pathogenesis have also been established. In collaboration with the McDonnell Genome Institute at Washington University, the investigators of the Genomics of AML Program Project Grant (PPG- TJ Ley, PI) sequenced the first human cancer genome (a patient with AML) and the first mouse cancer genome (from the mouse model of APL) and have discovered several new recurrent mutations that are important for AML pathogenesis and outcomes, including recurring mutations in DNMT3A and IDH1/2, among many others. These data are now being correlated to RNA expression, DNA methylation, histone modifications and chromatin structure, protein abundance and modification, and clinical datasets. Mouse models of epigenetic modifier mutations in AML are now being created and analyzed. These efforts will hopefully lead to new tests to better establish prognosis, and new approaches for the therapy of patients with this disease.

Model for evolution of genetic changes in acute myeloid leukemia

A hypothetical model in which nonpathogenic somatic mutations (1–3) acquired over the lifespan of a stem cell are propagated in the malignant clone after it acquires a critical initiating mutation (4). Mutation 5 is a progression mutation that cooperates with the AML-initiating mutation 4 to contribute to AML development. Other mutations (represented by 6 and 7) do not cooperate with the AML-initiating mutation 4, and do not contribute to AML development. These subclones are lost, or fail to expand to the limit of detection by sequencing studies.
AML: Acute myeloid leukemia; HSC: Hematopoietic stem cell.

From: Walter MJ, Graubert TA, DiPersio JF, Mardis ER, Wilson RK, Ley TJ
Next-generation sequencing of cancer genomes: back to the future.
Per Med 2009 Nov 1;6(6):653

Profiles (publications)

Biosketch

Education

  • 1978: MD, Washington University School of Medicine, St. Louis, MO
  • 1974: BA, Drake University, Des Moines, IA

Post-Graduate Training

  • 1984-1983: Hematology-Oncology Fellow, Washington University Medical Center, St. Louis, MO
  • 1983-1980: Clinical Associate, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD
  • 1980-1979: Assistant Resident in Medicine, Massachusetts General Hospital, Boston, MA
  • 1979-1978: Intern in Medicine, Massachusetts General Hospital, Boston, MA

Academic Positions & Employment

  • present-2021: Co-director, Physician Scientist Training Program, Department of Medicine, Washington University School of Medicine
  • present-2000: Director, Section of Stem Cell Biology, Division of Oncology, Washington University School of Medicine, St. Louis, MO
  • present-1993: Professor of Genetics, Washington University School of Medicine, St. Louis, MO
  • present-1993: Professor of Medicine, Washington University School of Medicine, St. Louis, MO
  • 2019-2008: Associate Director for Cancer Genomics, The Genome Institute, Washington University, St. Louis, MO
  • 2008-2000: Associate Director for Basic Science, Alvin J. Siteman Cancer Center, Washington University, St. Louis, MO
  • 2000-1994: Director, Hematopoiesis Research Center, Washington University School of Medicine, St. Louis, MO
  • 1993-1990: Associate Professor of Medicine, Washington University School of Medicine, St. Louis, MO
  • 1993-1986: Assistant Professor of Genetics, Washington University School of Medicine, St. Louis, MO
  • 1990-1986: Assistant Professor of Medicine, Washington University School of Medicine, St. Louis, MO
  • 1986-1984: Senior Investigator, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD

Board Certification

  • 1984: Hematology
  • 1981: Internal Medicine

Honors & Awards

  • 2022: 50th Leopold Griffuel Prize for Basic Science, French ARC Foundation for Cancer Research, Paris, France
  • 2022: Henry M. Stratton Medal, American Society of Hematology
  • 2019: Elected, National Academy of Sciences
  • 2016: Carl & Gerty Cori Award for Faculty Achievement, Washington University in St. Louis
  • 2016: David Workman Memorial Award, Samuel Waxman Cancer Research Foundation, New York, NY
  • 2015: Distinguished Faculty Award, Washington University Medical School
  • 2015: Erasmus Hematology Prize, Erasmus University, Rotterdam, Netherlands
  • 2015: Alfred G. Knudson Award for Cancer Genetics, National Cancer Institute
  • 2014: Distinguished Scientist Award, Association of American Cancer Institutes (AACI)
  • 2012: E. Donnall Thomas Prize, American Society of Hematology
  • 2012: Interdisciplinary/Collaborative Science Award, St. Louis Academy of Science
  • 2011: 2nd Century Award, Washington University
  • 2011-2007: Association of American Physicians Council (Treasurer 2008-2011)
  • 2010: Alumni Achievement Award, Drake University
  • 2010: American Academy of Arts and Sciences
  • 2009: Lewis T. and Rosalind B. Apple Chair in Oncology
  • 2008: American Society of Hematology Mentor Award
  • 2008: Distinguished Educator Award for Postdoctoral Mentoring, Washington University Medical School
  • 2007: Fellow, St. Louis Academy of Science
  • 2005: Herman Beerman Award, Society of Investigative Dermatology
  • 2003: National Academy of Medicine
  • 2002: Fellow of AAAS (American Association for the Advancement of Science)
  • 2001: Excellence in Teaching and Mentoring, Markey Special Emphasis Pathway, Washington University Medical School
  • 2001: St. Louis Spirit of Health Award, American Cancer Society
  • 2000: Internal Medicine Leadership Award in Scientific Investigation, Washington University Medical School
  • 2000: ASCI Special Service Award
  • 1999: MERIT Award, National Institutes of Health
  • 1999: Alan A. & Edith L. Wolff Professorship in Medicine
  • 1998: Alumni-Faculty Award, Washington University Medical School
  • 1995: Association of American Physicians
  • 1994: Teacher of the Year, Dept. of Medicine, Jewish Hospital
  • 1990: American Society for Clinical Investigation
  • 1988-1986: Basil O’Conner Scholar, March of Dimes Foundation
  • 1978: Alpha Omega Alpha Book Prize (Best Academic Record), Washington University, St. Louis, MO
  • 1978: Medical Fund Society Prize in Surgery, Washington University, St. Louis, MO
  • 1978: St. Louis Internists Club Book Prize (For Achievement in Medicine), Washington University, St. Louis, MO
  • 1978: Alpha Omega Alpha
  • 1976: Robert Carter Medical School Prize, Washington University, St. Louis, MO
  • 1975: E.V. Cowdry Prize in Histology, Washington University, St. Louis, MO
  • 1974: Phi Eta Sigma Award (Best Academic Record), Drake University
  • 1974: Ross Award for Promise of Success in Medicine, Drake University
  • 1974: Phi Beta Kappa, Drake University, Des Moines, IA

National Leadership Positions, Societies, & Boards

  • 2022-2015: National Cancer Advisory Board (Appointed by President Obama)
  • 2022-2007: International Cancer Genomics Consortium Scientific Planning Committee
  • 2022-1992: Cooley’s Anemia Foundation Medical Advisory Board
  • 2013-2008: NHGRI Board of Scientific Counselors (Chair, 2009-2013)
  • 2012-2008: Treasurer, Association of American Physicians
  • 2011-2007: Association of American Physicians Council
  • 2007-2004: American Society of Hematology, Awards Committee
  • 2005-2004: General Motors Foundation, Awards Committee
  • 2001-1998: FASEB Board of Directors
  • 1998-1997: President, American Society for Clinical Investigation
  • 1996-1992: Hematology I Study Section, ad hoc member
  • 1991-1990: Chairman, Committee on Scientific Affairs, American Society of Hematology

Professional Societies

  • Alpha Omega Alpha
  • American Society of Hematology
  • American Association for the Advancement of Science
  • American Society for Biochemistry and Molecular Biology
  • American Society for Clinical Investigation
  • Association of American Physicians