WASHINGTON UNIVERSITY SCHOOL OF MEDICINE DEPARTMENT OF MEDICINE

• Questions or comments
• Search this site

Our lab studies the pathogenesis of leukemia and multiple myeloma. These hematopoietic cancers are characterized by recurring chromosomal translocations that are associated with particular disease phenotypes and with clinical outcomes. The cloning and characterization of these chromosomal breakpoints has provided a rich supply of clinically relevant tools with which to model these diseases in animals and to explore molecular mechanisms of disease.

We are examining the TEL-PDGFRB fusion oncogene that is expressed as a result of the t(5;12) translocation exclusively in patients with chronic myelomonocytic leukemia (CMML), and the AML1-ETO fusion, which is expressed as a result of the t(8;21) translocation in patients with acute myeloid leukemia (AML). We have been examining the functional relevance of specific signal transduction pathways that are activated by TEL-PDGFRB in our mouse model of CMML. In this model, we express genes at a high level in the bone marrow of recipient mice using retroviral gene transduction followed by bone marrow transplantation into lethally irradiated syngeneic mice (mBMT).

In a second project, we have begun work to understand the mechanisms that underlie disease progression in CMML by coexpressing AML1-ETO and TEL-PDGFRB in mice. This recapitulates the progression to AML that occurred in our index case of CMML. It also serves as a paradigm for activating tyrosine kinase mutations cooperating with AML1-ETO to cause AML.

In studying putative downstream targets of TEL-PDGFRB, we found that the well-known oncogene Myc when expressed in our mBMT system, does not cause CMML, but rather results in the rapid onset of an AML phenotype. We are pursuing these data to further explore the model that a series of oncogenic "hits" that disrupt specific cellular pathways (e.g. cell cycle, apoptosis) are required to cause transformation and cancer.

Lastly, the newly identified MMSET gene is dysregulated in a subset of patients with multiple myeloma. This disease is incurable with current therapies, and patients expressing MMSET fare even worse than most. However, the function MMSET is unknown and we are pursuing several projects to functionally characterize this interesting gene.

Cytoplasmic tyrosine kinase gene expression in AML and normal myeloid cells RNA isolated from unfractionated AML bone marrow samples or from normal human bone marrow CD34+ cells, flow-sorted promyelocytes, and flow-sorted polymorphonuclear leukocytes was hybridized to Affymetrix U133 Plus 2 microarrays. Expression of cytoplasmic tyrosine kinase genes in our discovery set AML samples is rank-ordered from the highest to lowest levels of mean expression. AML samples are arranged by FAB classification. Expression levels are based on scaled signal intensity values for each probe set, with a value of 0 represented in green and 10 000 or greater as red. From: Tomasson MH, et al. 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

Education

1986	BA, Wesleyan University, Middletown, CT
1992	MD Stanford University, Stanford, CA

Post-graduate Training

1992-1998	American Board of Internal Medicine Research Training Pathway
1992-1994	Internship/Residency in Internal Medicine, Stanford University Hospital, Stanford, CA
1994-1998	Fellowship in Hematology/Oncology, Massachusetts General Hospital, Boston, MA
1997-1998	Rotating Clinical/Research Fellow in Medicine, Brigham and Women's Hospital, Boston, MA
1998-2000	Research Fellow in Medicine, Brigham and Women's Hospital, Boston, MA

Academic Positions

1997-2000	Instructor in Medicine, Harvard Medical School, Boston, MA
2000-2007	Assistant Professor of Medicine and Genetics, Washington University, St. Louis, MO
2007-present	Scientific Director, Siteman Cancer Center Myeloma Program
2007-present	Associate Professor of Medicine and Genetics, Washington University, St. Louis, MO

Appointments & Committees

1992	Stanford University School of Medicine Admissions Committee
1993	Stanford University Committee on Residency Training Improvement
1996-1998	Dana-Farber/Partners CancerCare Internet Steering Committee
2000	American Society of Hematology, Internet Task Force
2002-2005	American Society of Hematology, Education Committee
2004-2007	Siteman Cancer Center Patient Review and Monitoring Committee (PRMC)
2008-present	Washington University Human Research Protection Office/Institutional Review Board

Board Certification

1992	Diplomate, American Board of Internal Medicine
1997	Diplomate, Subspecialty of Medical Oncology
1998	Diplomate, Subspecialty of Hematology

Honors & Awards

1983-1984	Muscular Dystrophy Association Summer Scholar
1986	Mansfield Freeman Prize for East Asian Studies
1990-1991	Medical Student Scholars Program Award
1997	Lori Strauss Leukemia Foundation Award
1998-2000	Leukemia Society of America Fellow
2004	Leukemia and Lymphoma Society, Translational Research Award
2007	Hope Award, American Cancer Society

Professional Societies

	American Society of Hematology
	American Society of Clinical Oncology
	American Cancer Society - Leukemia and Immunobiology Study Section

• Updated: August 24, 2009s
•