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Education and Training:

M.D., University of Athens School of Medicine, Athens, Greece (1961)

Residency, in Medicine Department of Clinical Therapeutics and Hematology, University of Athens, Athens, Greece (1962-64)

Dr. Sci., University of Athens School of Medicine, Athens, Greece (1965)

Post-doctoral Trainee in Cell Biology and Tissue Culture, Department of Pathology, University of Washington, Seattle, WA (1965-67)

NIH Fellow and Senior Fellow, Division of Hematology, University of Washington, Seattle, WA (1968-73)

Thalia Papayannopoulou, M.D.
Professor of Medicine
Division of Hematology
University of Washington School of Medicine

Office Address:
University of Washington School of Medicine
Division of Hematology, Box 357710
1705 NE Pacific Street, HSB K-243
Seattle, WA 98195-7710

Phone:   (206) 543-5756
Fax:       (206) 543-3560; 543-3050
E-mail:   thalp@u.washington.edu


CURRENT CLINICAL INTERESTS

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


RESEARCH DESCRIPTION

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..

Other studies.  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.  


SELECTED PUBLICATIONS

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. 35:605-617, 2007.

Papayannopoulou Th, Scadden D: Stem cell ecology and stem cells in motion.  Blood 111(8):3923-30, 2008 (Review).