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Tucker W. LeBien, Ph.D.
Professor
Department of Laboratory Medicine and Pathology
Nebraska, 1977, Ph.D.
lebie001@tc.umn.edu
612-626-1422 - office
612-626-4839 - lab
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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.
- Hermanson, D., S.N Addo, A. Bajer, J. Marchant, S.G.K.
Das, B. Srinivasan, F. Al-Mousa, F. Michelangeli, D.D. Thomas,
T.W. LeBien*, and C. Xing*. 2009. Dual mechanisms of sHA
14-1 in inducing cell death through endoplasmic reticulum
and mitochondria. Molecular
Pharmacol. 76:667-678 (*co-senior authors).
- Xue, X., X. Huang, S.E. Nodland, L. Mates, L. Ma, Z. Izsvak,
Z. Ivics, T.W. LeBien, R.S. McIvor, J.E. Wagner, and X.
Zhou. 2009. Stable gene transfer and expression in cord
blood-derived CD34+ hematopoietic stem and progenitor cells
by a hyperactive Sleeping Beauty transposon system. Blood
114:1319-1330 (editorialized)
- Johnson, S.E., N. Shah, A. Bajer, and T.W. LeBien. 2008.
IL-7 activates the PI3K/AKT pathway in normal human thymocytes
but not normal human B-cell precursors. J.
Immunol. 180:8109-8117.
- LeBien, T.W. and T.F. Tedder. 2008. B-lymphocytes: how
they develop and function. Blood
112:1570-1580.
- LeBien, T.W. 2006. Battling bone marrow B-lineage cells.
Blood 108:1120.
- Johnson SE, Shah N, Panoskaltsis-Mortari A, and LeBien
TW. 2005. Murine and human IL-7 activate STAT5 and
induce proliferation of normal human pro-B cells.
J.
Immunol. 175:7325-7331.
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