Disorders of erythropoiesis, congenital or acquired
CURRENT RESEARCH INTERESTS
Erythroid differentiation and globin gene regulation; hemopoietic stem/progenitor cell trafficking; homing and mobilization mechanisms; and stem cell function
A major focus of research in our laboratory is the exploration of the mechanisms that
govern hematopoietic stem/progenitor cell trafficking. Cytoadhesive
interactions between hematopoietic cells and their microenvironment
are thought to be responsible for their specific localization and
development within discrete sites ("niches") in bone marrow.
Furthermore, dynamic changes in several adhesion molecules, especially
of the integrin family, functioning in concert with a large number of
other partners and with chemokines/growth factor receptors and their
ligands, seem to guide the trafficking of stem/progenitor cells in and
out of the marrow. Through a combination of approaches using
Abs, small molecules or mouse genetic models, we have shown that
the a4 integrin (VLA-4) is one of the major players in the regulation
of stem cell trafficking, however, the precise molecular pathways have
yet to be delineated. Other adhesion molecules and chemokines
seem to cooperate with alpha4 integrin or provide parallel effects,
and these represent another focus of our study.
We hope that this
comprehensive approach would shed light on the specific contributions
of particular molecules in hemopoietic cell homeostasis, in
hemopoietic cell trafficking, and in bone marrow homing and
regeneration. It is
important to emphasize that knowledge on these issues may have a
clinical relevance in the future for manipulating donor cells or
recipients to enhance engraftment..
Several collaborative studies involving globin gene regulation
and globin gene switching during ontogeny and the manipulation of
globin expression during adult life are also being pursued.
Papayannopoulou Th, Brice M, and Stamatoyannopoulos G:
Analysis of human hemoglobin switching in MEL x human fetal erythroid cell hybrids.
Cell 46:469-476, 1986.
Dzierzak EA, Papayannopoulou Th, Mulligan RC: Lineage-specific expression of a human ß-globin gene in murine bone marrow transplant recipients reconstituted with retrovirus-transduced stem cells.
Nature 331:35-41, 1988.
Papayannopoulou Th, Enver T, Takegawa S, Anagnou NP, and Stamatoyannopoulos G: Activation of developmentally mutated human globin genes by cell fusion.
Science 242:1056-1058, 1988.
Papayannopoulou Th, and Nakamoto B: Peripheralization of hemopoietic progenitors in primates treated with anti-VLA4 integrin.
PNAS USA 90:9274-9378, 1993.
Scott LM, Priestley GV, and Papayannopoulou Th: Ablation of a4 integrins in adult hematopoietic cells reveals roles in homeostasis, regeneration and homing.
MCB 23:9349-60, 2003.
Papayannopoulou Th: Bone marrow homing:
the players, the playfield, and their evolving roles. Current
Opinion in Hematology 10:214-219, 2003.
Papayannopoulou T: Current mechanistic scenarios in hematopoietic stem/progenitor cell mobilization.
Blood 103:1580-1585, 2003.
Chang K-H, Nelson AM, Cao H, Wang L, Nakamoto B,
Ware CB, and Papayannopoulou Th: Definitive-like erythroid
cells derived from human embryonic stem cells co-express high levels
of embryonic and fetal globins with little or no adult
globin. Blood 108:1515-1523, 2006.
Banerjee ER, Jiang Y, Henderson WR, Jr., Scott LM,
and Papayannopoulou Th: Alpha4 and beta2 integrins have
non-redundant roles for asthma development, but for optimal allergen
sensitization only alpha4 is critical. Exp. Hematol.
Papayannopoulou Th, Scadden D: Stem cell
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