WASHINGTON UNIVERSITY SCHOOL OF MEDICINE DEPARTMENT OF MEDICINE

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The lab focuses on the genetics and genomics of acute myeloid leukemia (AML). Several versions of a mouse model of acute promyelocytic leukemia have been created, which recapitulate most features of the human disease. These mice are being used as a platform to identify mutations that cooperate with PML-RARA, the fusion protein that is the consequence of the 15;17 translocation that is uniquely associated with this disease. The lab is studying human AML with a variety of genomic platforms in a long-term collaboration with the Genome Institute at Washington University. A variety of array based genomic studies have been used to identify copy number alterations in AML genomes, and expression signatures for several AML subtypes. In addition, whole genome sequencing has been initiated for a large number of AML samples with normal cytogenetics, or with the 15;17 translocation. We are attempting to identify recurring mutations that could potentially be used to better stratify patients with intermediate risk cytogenetics, so that more appropriate treatment intensity approaches can be used for these patients. A number of new, recurring mutations have now been identified, including mutations in the IDH1 and IDH2 genes, which appear to predict outcomes. We are also sequencing the genomes of the murine APL tumors from the models generated in the lab; in the first genome sequenced, we found recurring somatic mutations that are also detected in human AML patients, verifying the idea that progression mutations may be conserved. Integrated genomic approaches are being used to link changes in the genome, transcriptome, and methylome to the phenotypes and outcomes of AML patients, to identify new prognostic tests, and potential targets for therapy.

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

Education

1974	B.A., Drake University, Des Moines, IA
1978	M.D., Washington University School of Medicine, St. Louis, MO

Post-graduate Training

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

Academic Positions & Employment

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

Board Certification

1981	Internal Medicine
1984	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

Honors & Awards

1974	Phi Beta Kappa, Drake University, Des Moines, IA
1974	Ross Award for Promise of Success in Medicine, Drake University
1974	Phi Eta Sigma Award (Best Academic Record), Drake University
1975	E.V. Cowdry Prize in Histology, Washington University, St. Louis, MO
1976	Robert Carter Medical School Prize, Washington University, St. Louis, MO
1978	Alpha Omega Alpha
1978	St. Louis Internists Club Book Prize (For Achievement in Medicine), Washington University, St. Louis, MO
1978	Medical Fund Society Prize in Surgery, Washington University, St. Louis, MO
1978	Alpha Omega Alpha Book Prize (Best Academic Record), Washington University, St. Louis, MO
1986-1988	Basil O'Conner Scholar, March of Dimes Foundation
1990	American Society for Clinical Investigation
1994	Teacher of the Year, Dept. of Medicine, Jewish Hospital
1995	Association of American Physicians
1998	Alumni-Faculty Award, Washington University Medical School
1999	Alan A. & Edith L. Wolff Professorship in Medicine
1999	MERIT Award, National Institutes of Health
2000	ASCI Special Service Award
2000	Internal Medicine Leadership Award in Scientific Investigation, Washington University Medical School
2001	St. Louis Spirit of Health Award, American Cancer Society
2001	Excellence in Teaching and Mentoring, Markey Special Emphasis Pathway, Washington University Medical School
2002	Fellow of AAAS (American Association for the Advancement of Science)
2003	Institute of Medicine, National Academy of Sciences
2005	Herman Beerman Award, Society of Investigative Dermatology
2006	America’s Top Physicians, Consumers’ Research Council of America
2007	Fellow, St. Louis Academy of Science
2007-2011	Association of American Physicians Council (Treasurer 2008-2011)
2007	Best Doctors in America
2008	Distinguished Educator Award for Postdoctoral Mentoring, Washington University Medical School
2008	American Society of Hematology Mentor Award
2009	Lewis T. and Rosalind B. Apple Chair in Oncology
2009-2012	Who’s Who in America
2010	American Academy of Arts and Sciences
2010	Alumni Achievement Award, Drake University
2011	2nd Century Award, Washington University
2012	Interdisciplinary/Collaborative Science Award, St. Louis Academy of Science

National Leadership Positions, Societies, & Boards

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

Editorial Boards

1990-1996 1998-2003	Blood
1995-1998	Clinical Molecular Pathology
1998-2003	Journal of Clinical Investigation

• Updated: February 24, 2012
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