Wojciech Swat, PhD

Associate Professor, Pathology and Immunology
Office Suite B - 8210, BJCIH Building
Office: (314) 747-8886
Lab: (314) 747-8886
E-mail: swat@wustl.edu
Pub Med Search

Research

The lab interests have focused on molecular mechanisms underlying development of lymphoid cells. The dynamic process involving the commitment of pluripotent hematopoietic stem cells to various lymphoid lineages and subsequent maturation of progenitor cells is not entirely understood. These developmental programs involve modifications of gene expression controlled by both intrinsic and extrinsic cues resulting in lymphocyte survival, proliferation, differentiation and/or apoptosis.

The long term objective of studies conducted in this lab is to understand the molecular mechanisms underlying development of lymphoid lineages and activation of mature lymphocytes. In this context, several active projects focus on function of Discs large (Dlg) and Vav gene families of putative tumor supresors and protooncogenes, which are essential in signal transduction during normal develoment.

Our work involving generation and analyses of mice with gene knock-out indicates that Dlg and Vav proteins are essential for both adaptive and the innate immune system function. Unexpectedly, however, we also uncovered previously unknown functions of Vav proteins in phagocytic cell production of antimicrobial reactive oxygen species (ROS) and in development of osteoclast cells involved in the regulation of bone density. In addition, Vav is essential for the maintenance of epithelial cell-barrier in the gut. On the other hand, Dlg1 gene, which is implicted by studies conducted in our laboratory in mediating signals downstream of antigen receptors in T and B lymphocytes, is also crucial for renal branching morphogenesis in developing embryos.

Selected Publications

  • Swat W, Montgrain V, Doggett T, Douangpanya J, Puri K, Vermi W, Diacovo T. The essential role of PI3Kd and PI3Kg in thymocyte survival. Blood 2005, in the press, 2005

  • Faccio R, Teitelbaum SL, Fujikawa K, Chappel J, Zallone A, Tybulewicz VL, Ross FP, Swat W. Vav3 regulates osteoclast function and bone mass. Nature Med. Nature Med. 2005, 11: 284-290, 2005

  • Swat W, Fujikawa K. The Vav Family: At the crossroads of signaling pathways. Immunologic Res. 2005, 32, 259-266, 2005

  • Cella M, Fujikawa K, Tassi I, Kim S, Latinis K, Nishi S, Yokoyama W, Colonna M, Swat W. Differential requirements for Vav proteins in DAP10- and ITAM-mediated NK cell cytotoxicity. J Exp Med. 2004 200 :817-23, 2004

  • Xavier R, Rabizadeh S, Ishiguro K, Andre N, Ortiz JB, Wachtel H, Morris DG, Lopez-Ilasaca M, Shaw AC. Discs large (Dlg1) complexes in lymphocyte activation. J Cell Biol. 2004 166 :173-8, 2004

  • Gakidis MA, Cullere X, Olson T, Wilsbacher JL, Zhang B, Moores SL, Ley K, Swat W, Mayadas T, Brugge. Vav GEFs are required for beta2 integrin-dependent functions of neutrophils. J Cell Biol. 2004 166 :273-82, 2004

  • Fujikawa K, Miletic AV, Alt FW, Faccio R, Brown T, Hoog J, Fredericks J, Nishi S, Mildiner S, Moores. Vav1/2/3-Null Mice Define an Essential Role for Vav family Proteins in Lymphocyte Development and Activation but a Differential Requirement in MAPK Signaling in T and B cells. J Exp Med. 2003, 198(10):1595-608, 2003

  • Sicinska E, Aifantis I, Le Cam L, Swat W, Borowski C, Yu Q, Ferrando A, Levin S, Geng Y, von Boehmer. Requirement for cyclin D3 in lymphocyte development and leukemias. Cancer Cell. 2003, 4:451-61, 2003

  • Ned RM, Swat W, Andrews NC. Transferrin receptor 1 is differentially required in lymphocyte development. Blood. 2003, 102(10):3711-8, 2003

  • Miletic AV, Swat M, Fujikawa K, Swat W. Cytoskeletal remodeling in lymphocyte activation. Curr Opin Immunol. 2003, 15: 261-268, 2003

  • Swat W, Xavier R, Mizoguchi A, Mizoguchi E, Fredericks J, Fujikawa K, Bhan AK and Alt FW. Essential Role for Vav1 in Activation, but not Development of __ T Cells. Int Immunol 2003, 15: 215-221, 2003

  • Bassing CH, Swat W, Alt FW. The mechanism and regulation of chromosomal V(D)J recombination. Cell 2002, 109: S45-55, 2002

  • Brewer JA, Sleckman BP, Swat W, Muglia LJ. Green fluorescent protein-glucocorticoid receptor knockin mice reveal dynamic receptor modulation during thymocyte development. J Immunol 2002, 169: 1309-1318, 2002

  • Fujikawa K, Inoue Y, Sakai M, Koyama Y, Nishi S, Funada R, Alt FW and Swat W. Vav3 is regulated during the cell cycle and effects cell division. Proc Natl Acad Sci USA 2002, 99: 4313-4318, 2002

  • Brewer JA, Vogt SK, Sleckman BP, Swat W, Kanagawa O, Muglia LJ. Knock-ins and conditional knockouts: in vivo analysis of glucocorticoid receptor regulation and function. Endocr Res 2002, 28: 545-550, 2002

  • Moores SL, Selfors LM, Fredericks J, Breit T, Fujikawa K, Alt FW, Brugge JS and Swat W. Vav family proteins couple to diverse cell surface receptors. Mol Cell Biol 2000, 20: 6364-6373, 2000

  • Gaertner F, Alt FW, Monroe R, Chu M, Sleckman BP, Davidson L, Swat W. Immature thymocytes employ distinct signaling pathways for allelic exclusion versus differentiation and expansion. Immunity 1999, 10: 537-546, 1999

  • Shaw AC, Swat W, Davidson L, Alt FW. Regulation of immunoglobulin light chain gene rearrangement in _ heavy chain-deficient B cells by activated Ras. Proc Natl Acad Sci USA 1999, 96: 2239-2243, 1999

  • Shaw AC, Swat W, Ferrini R, Davidson L, Alt FW. Activated Ras signals progression of recombination deficient pro-B lymphocytes. J Exp Med 1999, 189: 123-129, 1999

  • Wang LC, Swat W, Fujiwara Y, Davidson L, Visvader J, Kuo F, Alt FW, Gilliland DG, Golub TR, Orkin SH. The TEL/ETV6 gene is required specifically for hematopoiesis in the bone marrow. Genes and Dev 1998, 12: 2392-2402, 1998

  • Holsinger LJ, Graef IA, Swat W, Chi T, Bautista DM, Davidson L, Lewis RS, Alt FW, Crabtree GR. Defects in actin-cap formation in Vav-deficient mice implicate an actin requirement for lymphocyte signal transduction. Current Biology 1998, 8: 563-572, 1998

  • Gao Y, Sun Y, Frank KM, Dikkes P, Fujiwara Y, Seidl KJ, Sekiguchi JM, Rathbun GA, Swat W, Wang J, Br. A critical role for DNA end-joining proteins in both lymphogenesis and neurogenesis. Cell 1998, 95: 891-902, 1998

  • Frank KM, Sekiguchi JM, Seidl KJ, Swat W, Rathbun GA, Cheng HL, Davidson L, Kangaloo L, Alt FW. Late embryonic lethality and impaired V(D)J recombination in mice lacking DNA ligase IV. Nature 1998, 396:173-177, 1998

  • Swat W, Fujikawa K, Ganiatsas S, Yang D, Xavier RJ, Harris NL, Davidson L, Ferrini R, Davis RJ, Labo. SEK1/MKK4 is required for maintenance of a normal peripheral lymphoid compartment but not for lymphocyte development. Immunity 1998, 8: 625-634, 1998

  • Willerford DM, Swat W, Alt FW. Developmental regulation of V(D)J recombination and lymphocyte differentiation. Current Opinion in Genetics and Development 1996,, 1996

  • Porcher C, Swat W, Rockwell K, Fujiwara Y, Alt FW, Orkin SH. The T-cell leukemia oncoprotein SCL/tal-1 is essential for development of all hematopoietic lineages. Cell 1996, 86: 47-57, 1996

  • Swat W, Shinkai Y, Cheng H-L, Davidson L, Alt FW. Activated Ras signals differentiation and expansion of CD4+8+ thymocytes. Proc Natl Acad Sci USA 1996, 93: 4683-4687, 1996

  • Zhang R, Alt FW, Davidson L, Orkin SH, Swat W. Defective signalling through the T- and B-cell antigen receptors in lymphoid cells lacking the vav proto-oncogene. Nature 1995, 374: 470-473, 1995

  • Rodewald HR, Kretzschmar K, Swat W, Takeda S. Intrathymically expressed c-kit ligand (stem cell factor) is a major factor driving expansion of very immature thymocytes in vivo. Immunity 1995, 3: 313-319, 1995

  • Fehling HJ, Swat W, Laplace C, Kühn R, Rajewski K, Müller U, von Boehmer H. MHC class I expression in mice lacking proteasome subunit LMP-7. Science 1994; 265: 1234-1237, 1994

  • Swat W, von Boehmer H, Kisielow P. Small CD4+8+TCRlow thymocytes contain precursors of mature T cells. Eur J Immunol 1994; 24:1010-1012, 1994

  • Swat W, von Boehmer H, Kisielow P. Central tolerance: clonal deletion or clonal arrest?. Eur J Immunol 1994; 24:485-487, 1994

  • Swat W, Dessing M, von Boehmer H, Kisielow P. CD69 expression during selection and maturation of CD4+8+ thymocytes. Eur J Immunol 1993; 23:739-746, 1993

  • Swat W, Dessing M, Baron A, Kisielow P, von Boehmer H. Phenotypic changes accompanying positive selection of CD4+CD8+ thymocytes. Eur J Immunol 1992; 22:2367-2372, 1992

  • Swat W, Ignatowicz L, von Boehmer H, Kisielow P. Clonal deletion of immature CD4+8+ thymocytes in suspension culture by extrathymic antigen-presenting cells. Nature 1991; 351:150-153, 1991

DBBS Graduate Program Affiliation

Department of Pathology and Immunology
Campus Box 8118
660 South Euclid Ave.
St. Louis, MO 63110
 
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