PRIMARY FACULTY

Gabriela Dveksler, Ph.D.
Professor
Pathology
 
4301 Jones Bridge Road
Bethesda MD 20814
Office: 301-295-3332
Fax: 301-295-1996
gdveksler@usuhs.mil

We are studying the functions of members of the carcinoembryonic antigen (CEA) gene family, known as pregnancy specific glycoproteins (PSGs). PSGs are expressed in the placenta of rodents and humans, which share the same type of placentation, known as hemochorial. PSGs are secreted into the maternal circulation in increasing amounts, until term. In our laboratory, we are using molecular biology and immunology techniques to understand the function of the 17 murine and of the 11 human pregnancy specific glycoprotein family members. It is still unknown whether all PSGs share the same function(s) and utilize the same receptor (s). We generated several human and murine recombinant PSGs and identified their ability to regulate the secretion of cytokines. PSG target cells include immune cells such as T cells and monocyte/macrophages. In addition, PSGs bind to endothelial cells and trophoblasts. One important function of PSGs is their ability to induce transforming growth factor beta 1 (TGF?1) in all the cell types mentioned above. TGF?1 is an important immunoregulatory molecule as well as a potent pro-angiogenic factor. We have found that in addition to TGF?1, some PSGs induce vascular endothelial growth factor and reduce the ability of T cells to secrete IL-2. Therefore, our studies indicate that PSGs are involved in two processes, which are essential for pregnancy success: the establishment of the fetal-maternal blood supply and the regulation of the immune responses to the semi-allogeneic fetus. In addition to the identification of the function of PSGs, our laboratory is involved in the characterization of the cellular receptor(s) for PSGs in target cells. We have identified the tetraspanin CD9 as the receptor for murine pregnancy specific glycoproteins 17 and 19.

Selected Publications:

R. Waterhouse, C. Ti and G. S. Dveksler. Murine CD9 is the Receptor for Pregnancy Specific Glycoprotein 17. J. Exp. Med. 195:277-82 (2002).
 
D. Ellermann, C. Ha, D. Myles, P. Primakoff and G. Dveksler. Direct Binding of the Ligand PSG17 to CD9 at a site active in sperm-egg fusion. Mol. Biol. Cell.14: 5098-103 (2003).
 
A. McLellan, B. Fischer, H. Hameister, G. Dveksler, T. Hori, F. Wynne, M. Ball, K. Okumura, T. Moore and W. Zimmermann. Structure and evolution of the mouse pregnancy-specific glycoprotein gene locus. BMC Genomics 6 (1):4 (2005).
 
B. F. Bebo Jr. and G. Dveksler. Evidence that Pregnancy specific glycoproteins regulate T-cell function and inflammatory autoimmune disease during pregnancy. Current Drug Targets in Inflammation and Allergy, 2:231-237 (2005).
 
C. T. Ha, R. Waterhouse, J. Wessells, J. A. Wu and G. Dveksler. Binding of pregnancy specific glycoprotein 17 to CD9 on macrophages induces secretion of IL-10, IL-6, PGE2, and TGF?1. J. of Leukocyte Biology, 77:948-957 (2005).
 
C. T. Ha, R. Waterhouse, J. Warren , W. Zimmermann and G. Dveksler. N-glycosylation is required for binding of murine pregnancy-specific glycoproteins 17 and 19 to the receptor 19. Am J Reprod Immunol, 50:251-258 (2008)
 
J Wu, B. Johnson, Y. Chen, C. Ha and G. Dveksler. Murine pregnancy-specific glycoprotein 23 induces the proangiogenic factors transforming -growth factor beta 1 and vascular endothelial growth factor A in cell types involved in vascular remodeling in pregnancy. Biology of Reproduction, In press.

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