WASHINGTON UNIVERSITY SCHOOL OF MEDICINE DEPARTMENT OF MEDICINE

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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.

MSCV-Myc induces myeloid and lymphoid disease phenotypes simultaneously in Ink4a-/- mice, and myeloid leukemia exclusively in Ink4a+/+ mice MycInk4a-/- mice show a mixture of myeloid and lymphoid blast cells in the bone marrow (BM), and lymphoid blasts in the lymph nodes (LN) and thymus (Thy). MycInk4a+/+ mice show only myeloid blasts in the bone marrow and lymph nodes, and normal-appearing cells in thymus. From: Luo H, Li Q, O'Neal J, Kreisel F, Le Beau MM, Tomasson MH c-Myc rapidly induces acute myeloid leukemia in mice without evidence of lymphoma-associated antiapoptotic mutations. Blood 2005 Oct 1;106(7):2452-61

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
2000-2008	Assistant Professor of Medicine and Genetics, Washington University, St. Louis, MO
2007-present	Scientific Director, Siteman Cancer Center Myeloma Program
2008-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)

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

Editorial Responsibilities

	Blood – ad hoc reviewer
	Leukemia – ad hoc reviewer
	Stem Cells – ad hoc reviewer

Professional Societies

	American Society of Hematology
	American Society of Clinical Oncology

Updated: June 30, 2008