WASHINGTON UNIVERSITY SCHOOL OF MEDICINE DEPARTMENT OF MEDICINE

• Questions or comments
• Search this site

My laboratory studies the molecular pathogenesis of myeloid leukemias. We are interested in defining inherited genetic susceptibility factors and somatically acquired mutations important for disease initiation and progression. Specific diseases of interest to our group include: the myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and MDS/AML arising as a consequence of prior chemotherapy (t-MDS/AML). Both mouse models and correlative studies using human samples are utilized.

Current projects include:

Genomics of myelodysplastic syndromes. A large panel of primary human MDS and patient-matched normal (germline) samples have been obtained. Samples are screened for acquired DNA lesions by high-throughput gene resequencing, array-based comparative genomic hybridization, and array-based mRNA/miRNA profiling. Novel mutations are further characterized using tissue culture and mouse model systems.

Susceptibility to therapy-related MDS/AML (t-MDS/AML). This project addresses the hypothesis that the risk of iatrogenic secondary leukemias is influenced by inherited genetic susceptibility factors. We are testing this hypothesis in human populations by candidate gene and genome-wide association studies. In addition, we have identified inbred mouse strains that are susceptible or resistant to t-MDS/AML. Intercross strategies are utilized to define the underlying genetic basis of t-MDS/AML susceptibility in mice.

Identification of copy number variants. In addition to single nucleotide polymorphisms (SNPs), large scale DNA copy number gains and losses are an important source of germline genetic variation in mammalian genomes. We are using array-based comparative genomic hybridization to measure copy number variation in mouse and human genomes. We have developed novel bioinformatic tools to identify copy number variants, define their boundaries, and relate these gains and losses to phenotypic variation in mice and humans.

Chromosomal deletions in patients with myelodysplastic syndrome (A) Diagram of the region on the long arm of human chromosome 5q31.2 that is commonly deleted in patients with MDS. (B) A custom high resolution oligonucleotide array containing 385,000 probes across human chromosome 5 was used to measure copy number in DNA samples from MDS bone marrow cells compared to matched, unaffected tissue (skin) from the same patient. The negative log2 ratio between 86.2 Mbp and 155.7 Mbp (arrows) reflects an acquired (somatic) copy number deletion in the MDS sample. (C) Expanded view demonstrates monoallelic copy number loss within the commonly deleted interval. From: Graubert TA, Payton MA, Shao J, Walgren RA, Monahan RS, Frater JL, Walshauser MA, Martin MG, Kasai Y, Walter MJ Integrated genomic analysis implicates haploinsufficiency of multiple chromosome 5q31.2 genes in de novo myelodysplastic syndromes pathogenesis. PLoS ONE 2009;4(2):e4583

Education

1984	BA (Biology and Philosophy), Dartmouth College, Hanover, NH
1988	MD, Harvard University, Boston, MA

Post-graduate Training

1988-1989	Intern in Internal Medicine, Yale-New Haven Hospital, New Haven, CT
1989-1991	Resident in Internal Medicine, Yale-New Haven Hospital, New Haven CT
1991-1993	Research Fellow in Hematology (Nancy Berliner lab), Yale School of Medicine, New Haven, CT
1993-1995	Fellow in Hematology-Oncology, Washington University School of Medicine, St. Louis, MO
1995-1999	Post-doctoral Research Associate (Tim Ley lab), Washington University School of Medicine, St. Louis, MO

Academic Positions

1997-1999	Instructor, Department of Medicine, Washington University School of Medicine, St. Louis, MO
1997-present	Attending Physician, Barnes-Jewish Hospital, St. Louis, MO
1999-2007	Assistant Professor, Departments of Medicine and Pathology & Immunology, Washington University School of Medicine, St. Louis, MO
1999-2007	Research Associate Member, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO
2001-present	Director, High Speed Cell Sorter Core Laboratory, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO
2007-present	Associate Professor, Departments of Medicine and Pathology & Immunology, Washington University School of Medicine, St. Louis, MO

Appointments & Committees

2002-2005	Organizer, Stem Cell Biology Group, Washington University School of Medicine
2003	Organizing Committee for Stem Cell Symposium, Washington University School of Medicine
2004-present	Oncology Fellowship Training Committee

Board Certification

1991-2012	Internal Medicine (ABIM)
1997-2017	Medical Oncology (ABIM)

Honors & Awards

1984	Rufus Choate Scholar, Dartmouth College
1984	Phi Beta Kappa, Dartmouth College
1984	Summa cum laude, Dartmouth College
1984-1988	Alfred K. Priest Fellowship
1985	Harvard Summer Research Award
1999-2004	Physician-Scientist Training Grant, NHLBI, NIH
2000	Faculty Scholar Award, American Society of Hematology
2001	Excellence in Mentoring Award, Washington University

Professional Societies & Organizations

1988-1990	American Medical Association
1992-present	American Society of Hematology
1993-1995	American College of Physicians
2005	NIH Clinical Oncology (CONC) Study Section, ad hoc
2006, 2007	ASH subcommittee on AML, abstract review panel and session moderator
2007	NIH Modeling and Analysis of Biological Systems (MABS) study section, ad hoc
2007-2010	Leukemia & Lymphoma Society study section, Translational Research Program
2008	NIH Hematopoiesis (HP) Study Section, ad hoc

• Updated: June 15, 2009
•