Michael Tomasson, M.D.

DEPARTMENT OF Internal Medicine
Keywords: oncogene, cancer, hematopoiesis, pathogenesis, signal transduction, tumor biology

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.