Research Description

Human tumors are characterized by recurring chromosomal abnormalities. During the past few years, the genes that are located at the breakpoints of a number of recurring chromosomal abnormalities in human tumors have been identified. Molecular analysis has revealed that alterations in the level of expression of these genes, or in the properties of the encoded proteins resulting from the chromosomal rearrangement, play an integral role in the process of malignant transformation. My research interests are:

• to identify the recurring chromosomal abnormalities in human tumors;
• to correlate specific chromosomal abnormalities with morphological and clinical features of the neoplastic disease, such as response to therapy and survival;
• to identify the genes located at the breakpoints of the recurring abnormalities using the techniques of molecular genetics, and to examine their function in malignant cells characterized by these chromosomal abnormalities;
• to localize genes to human chromosomes by using the technique of in situ chromosomal hybridization and to examine the location of specific genes relative to the breakpoints of recurring abnormalities in hematopoietic neoplastic diseases; and
• to examine the relationship of chromosomal fragile sites (loci which are prone to undergo breakage and rearrangement) and cancer-specific breakpoints.

Selected Publications

Smith SM, Le Beau MM, Huo D, Karrison T, Sobecks RM, Anastasi J, Vardiman JW, Rowley JD, Larson RA.  Clinical-cytogenetic associations in 306 patients with therapy-related myelodysplasia and myeloid leukemia:  the University of Chicago series.  Blood 102:43-52, 2003.

Lucas I, Palakodeti A, Jiang Y, Young DJ, Jiang N, Fernald AA, Le Beau MM.  High throughput mapping of origins of replication in human cells. EMBO Rep 8:770-777, 2007.

Joslin JM, Fernald AA, Tennant TR, Davis EM, Kogan SC, Anastasi J, Crispino JD, Le Beau MM.  Haploinsufficiency of EGR1, a candidate gene in the del(5q), leads to the development of myeloid disorders.  Blood 110:719-726, 2007.

Qian Z, Chen L, Fernald AA, Williams BO, Le Beau MM. A critical role for Apc in hematopoietic stem and progenitor cell survival. J Exp Med 205:2163-75, 2008.

Shannon KM, Le Beau MM. Cancer: hay in a haystack.  Nature 451:252-253, 2008.

Jiang Y, Lucas I, Young DJ, Davis EM, Karrison T, Rest JS, Le Beau MM. Common fragile sites are characterized by histone hypoacetylation.  Hum Mol Genet 18:4501-4512, 2009.

Wang J, Fernald AA, Anastasi J, Le Beau MM, Qian Z. Haploinsufficiency of Apc leads to ineffective hematopoiesis. Blood 115:3481-3488, 2010.

Palakodeti A, Lucas I, Jiang Y, Young DJ, Fernald AA, Karrison T, Le Beau MM.  Impaired replication dynamics at the FRA3B common fragile site. Hum Mol Genet 19:99-110, 2010.