Associate Director for Basic Research
Research Program: Immunology
Director, M.D./Ph.D. Program
Professor, Department of Laboratory Medicine and Pathology

lebie001@umn.edu
612-626-1422 — office
612-626-4839 — lab
Preferred contact method: E-mail

Dr. LeBien received his Ph.D. in Medical Microbiology (Immunology) in 1977 from the University of Nebraska Medical Center. He conducted postdoctoral training in the laboratory of Dr. John Kersey in the Department of Laboratory Medicine and Pathology at the University of Minnesota. He joined the Masonic Cancer Center in 1994, where he conducts research on normal and abnormal human B cell development.

Research Interests

Normal and abnormal human B cell development. Normal B cell precursors and their leukemic counterparts in B cell precursor acute lymphoblastic leukemia (ALL) are poised to undergo different fates, including: survival, proliferation, differentiation, or apoptosis. Our laboratory has parallel interests in investigating the role of the bone marrow microenvironment in regulating the fate of normal and leukemic human B cell precursors. We have established a panel of human B cell precursor ALL cell lines that retain a dependency on human marrow stromal cells for survival and proliferation. These novel cell lines are facilitating the analysis of marrow stromal cell-derived molecules that regulate B cell precursor fates, the signaling pathways in B cell precursors that promote survival, the biochemical basis of cell death that follows loss of marrow stromal cell signaling, and the genetic basis of tumor progression that underlies the evolution of a leukemic clone from a stromal cell-dependent to a stromal cell-independent phenotype.

A related project employs a xenogeneic model system that supports human B-cell development from CD34+ cord blood stem cells using a murine marrow stromal cell microenvironment. This model has recently been exploited to implicate IL-7 as a replicative signal in human B-cell development. It is currently being used to characterize: a) the intracellular signaling pathways activated by IL-7, b) the role of marrow microenvironment-derived cytokines in cooperating with IL-7, and c) the outcome of modifying gene expression in B cell precursors (using retroviral vectors and RNA interference) on their developmental fate. The long-term goal is to elucidate the biochemical basis that distinguishes survival and death in developing B-lineage cells, and perturbations in B-lineage ALL that suppress cell death and promote clonal expansion.

Selected Publications

Shah, N., L. Oseth, H. Tran, B. Hirsch, and T.W. LeBien. Clonal variation in the B-lineage acute lymphoblastic leukemia response to multiple cytokines and bone marrow stromal cells. Cancer Res. 2001; 61:5268-5274.

Bertrand, F.E., C. Vogtenhuber, N. Shah, and T.W. LeBien. Pro-B to pre-B cell development in B-lineage acute lymphoblastic leukemia expressing the MLL/AF4 fusion protein. Blood 2001;98:3398-3405.

LeBien, T.W. Arginine: an unusual dietary requirement of preB lymphocytes. J. Clin. Invest., 2003;110:1411-1413.

Bertrand FE, Spengeman J, Shah N, and LeBien TW. B cell development in the presence of the MLL/AF4 oncoprotein proceeds in the absence of HOX A7 and HOX A9 expression. Leukemia 2003;17:2454-2459.

Burrows PD, LeBien TW, Zhang Z, Davis RS, and Cooper MD. The development of human B-lymphocytes. In: Molecular Biology of B cells; Honjo T, Alt FW, Neuberger M, eds. Elsevier Academic Press, pp141-154. 2004.

Shah N, Asch RJ, Lysholm AS, and LeBien TW. Enhancement of stress-induced apoptosis in B- ineage cells by caspase-9 inhibitor. Blood 2004;104:2873-2878.

Johnson SE, Shah N, Panoskaltsis-Mortari A, and LeBien TW. Murine and human IL-7 activate STAT5 and induce proliferation of normal human pro-B cells. J. Immunol. 2005;175:7325-7331.

LeBien TW. Lymphopoiesis: In: Williams Hematology, Seventh Edition. M.A. Lichtman, E. Beutler, T.J. Kipps, U. Seligsohn, K. Kaushansky, and J.T. Prchal eds. McGraw-Hill Medical, 1039-1049, 2006.

Johnson SE, Shah N, Bajer A, and LeBien TW. IL-7 activates the PI3K/AKT pathway in normal human thymocytes but not normal human B-cell precursors. J Immunol. 2008;180:8109-8117.

LeBien TW, Tedder TT. B-lymphocytes: How they develop and function. Blood (invited review as part of 50th anniversary celebration). In press.