Michael Tomasson, M.D.
Assistant Professor
Internal Medicine
Genetics
Molecular Cell Biology Program
Molecular Genetics and Genomics Program
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Office Phone: 314-362-9350
Lab Phone: 314-362-9368
Other Phone:
FAX: 314-362-9333
Box: 8007
Lab Address: 613L Southwest Tower
Email: tomasson@wustl.edu
Keywords: oncogene; cancer; hematopoiesis; pathogenesis; signal transduction; tumor biology
Short Research Description: Chromosomal translocations, fusion oncogenes, and the molecular pathogenesis of leukemia. |
Research Abstract:
My laboratory explores cancer biology with a particular focus on the pathogenesis of hematopoietic malignancies. Leukemia in humans in frequently associated with non-random chromosomal translocations and the fusion proteins expressed as a result can be used as tools to study these diseases. One family of these leukemia-associated fusion proteins are constitutively active tyrosine kinases of which BCR/ABL and TEL/PDGFBetaR are members. Expression of these oncogenes in mice cause a rapidly fatal myeloproliferative disease with many features of the human disease, and we are using this as a model system to study the molecular mechanisms of leukemogenesis and to test novel therapeutic strategies.
Although activated receptor tyrosine kinases (RTK) contribute to leukemogenesis, they are not sufficient to cause acute leukemia. Like other cancers, leukemia is thought to occur as a result of an accumulation of genetic events, and we have found that RTKs cooperate with transcription factor fusion oncogenes, such as AML1-ETO, to transform hematopoietic cells. We are interested in understanding the mechanisms that underlie this cooperation.
Another project in the lab involves multiple myeloma (MM). MM is a neoplasm of terminally differentiated B-cell lineage cells that causes debilitating bone destruction and is incurable with current therapies. The t(4;14) chromosomal translocation occurs in about 30% of cases of multiple myeloma, and results in the overexpression of novel gene, MMSET, that has not been characterized. We are interested in this gene and the role it may play in disease pathogenesis. |
Selected Publications:
Devine SM, Brown RA, Mathews V, et al. Reduced risk of acute GVHD following mobilization of HLA-identical sibling donors with GM-CSF alone. Bone Marrow Transplant 2005 36:531-538.
Luo H, Li Q, O'Neal J, et al. c-Myc rapidly induces acute myeloid leukemia in mice without evidence of lymphoma-associated antiapoptotic mutations. Blood 2005 106:2452-2461.
Cain JA, Grisolano JL, Laird AD, Tomasson MH. Complete remission of TEL-PDGFRB-induced myeloproliferative disease in mice by receptor tyrosine kinase inhibitor SU11657. Blood 2004 104:561-564.
Grisolano J, O’Neal J, Cain J, Tomasson MH. An activated tyrosine kinase, TEL-PDGFBetaRB, cooperates with AML1-ETO to cause acute myloid leukemia in mice. Proc Natl Acad Sci USA 2003 100:9506-9511.
Ley TJ, Minx PJ, Walther MJ, et al. A pilot study of high-throughput, sequence-based mutational profiling of primary human acute myeloid leukemia (AML) cell genomes. Proc Natl Acad Sci USA 2003 100:14275-14280. |