SITE SEARCH


Faculty > Faculty By Research Interest > 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.

Service to the University

PresentCourse Co-Director, Advanced Topics in Immunology 5272
PresentLecturer, Foundations of Immunology 5051
PresentLecturer, Contemporary Molecular Immunology 530

DBBS Graduate Program Affiliation

Immunology Program

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


Current Trainees

Ana Miletic
Linda Stephenson, PhD

Past Trainees

Graduate Students
Courtney Corman

Postdoctoral Fellows
Daniel Graham, PhD

Research Associates
Benedicte Sammut, PhD