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

Activation of Wnt/β-catenin protein signaling induces mitochondria-mediated apoptosis in hematopoietic progenitor cells.

Ming M, Wang S, Wu W, Senyuk V, Le Beau MM, Nucifora G, Qian Z

(Jun 2012) The Journal of biological chemistry 287(27):22683-90 PMID:22589536 (Full Text)

Impaired replication dynamics at the FRA3B common fragile site.

Palakodeti A, Lucas I, Jiang Y, Young DJ, Fernald AA, Karrison T, Le Beau MM

(Jan 2010) Human molecular genetics 19(1):99-110 PMID:19815620 (Full Text)

Cancer: hay in a haystack.

Shannon KM, Le Beau MM

(Jan 2008) Nature 451(7176):252-3 PMID:18202630

Haploinsufficiency of EGR1, a candidate gene in the del(5q), leads to the development of myeloid disorders.

Joslin JM, Fernald AA, Tennant TR, Davis EM, Kogan SC, Anastasi J, Crispino JD, Le Beau MM

(Jul 2007) Blood 110(2):719-26 PMID:17420284 (Full Text)

High-throughput mapping of origins of replication in human cells.

Lucas I, Palakodeti A, Jiang Y, Young DJ, Jiang N, Fernald AA, Le Beau MM

(Aug 2007) EMBO reports 8(8):770-7 PMID:17668008 (Full Text)

Clinical-cytogenetic associations in 306 patients with therapy-related myelodysplasia and myeloid leukemia: the University of Chicago series.

Smith SM, Le Beau MM, Huo D, Karrison T, Sobecks RM, Anastasi J, Vardiman JW, Rowley JD, Larson RA

(Jul 2003) Blood 102(1):43-52 PMID:12623843

A critical role for Apc in hematopoietic stem and progenitor cell survival.

Qian Z, Chen L, Fernald AA, Williams BO, Le Beau MM

(Sep 2008) The Journal of experimental medicine 205(9):2163-75 PMID:18725524 (Full Text)

Haploinsufficiency of Apc leads to ineffective hematopoiesis.

Wang J, Fernald AA, Anastasi J, Le Beau MM, Qian Z

(Apr 2010) Blood 115(17):3481-8 PMID:20065296 (Full Text)

Common fragile sites are characterized by histone hypoacetylation.

Jiang Y, Lucas I, Young DJ, Davis EM, Karrison T, Rest JS, Le Beau MM

(Dec 2009) Human molecular genetics 18(23):4501-12 PMID:19717471 (Full Text)

New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge.

Schanz J, Tüchler H, Solé F, Mallo M, Luño E, Cervera J, Granada I, Hildebrandt B, Slovak ML, Ohyashiki K, Steidl C, Fonatsch C, Pfeilstöcker M, Nösslinger T, Valent P, Giagounidis A, Aul C, Lübbert M, Stauder R, Krieger O, Garcia-Manero G, Faderl S, Pierce S, Le Beau MM, Bennett JM, Greenberg P, Germing U, Haase D

(Mar 2012) Journal of clinical oncology : official journal of the American Society of Clinical Oncology 30(8):820-9 PMID:22331955