wiskott aldrich syndrome

Summary

Summary: A rare, X-linked immunodeficiency syndrome characterized by eczema, thrombocytopenic purpura, and recurrent pyogenic infection. It is seen exclusively in young boys. Typically, IMMUNOGLOBULIN M levels are low and IMMUNOGLOBULIN A and IMMUNOGLOBULIN E levels are elevated. Lymphoreticular malignancies are common.

Top Publications

  1. ncbi Autoimmunity in Wiskott-Aldrich syndrome: risk factors, clinical features, and outcome in a single-center cohort of 55 patients
    Sophie Dupuis-Girod
    Unité d Immunologie et d Hématologie Pédiatriques, Hopital Necker Enfants Malades, Paris, France
    Pediatrics 111:e622-7. 2003
  2. ncbi Wiskott-Aldrich syndrome protein-deficient mice reveal a role for WASP in T but not B cell activation
    S B Snapper
    Howard Hughes Medical Institute, Children s Hospital, Boston, Massachusetts 02115, USA
    Immunity 9:81-91. 1998
  3. pmc Early deficit of lymphocytes in Wiskott-Aldrich syndrome: possible role of WASP in human lymphocyte maturation
    J Y Park
    The CBR Institute for Biomedical Research, Harvard Medical School, Boston 02115, USA
    Clin Exp Immunol 136:104-10. 2004
  4. ncbi A lentiviral vector encoding the human Wiskott-Aldrich syndrome protein corrects immune and cytoskeletal defects in WASP knockout mice
    S Charrier
    Genethon UMR CNRS 8115, Evry, France
    Gene Ther 12:597-606. 2005
  5. pmc Wiskott-Aldrich syndrome protein regulates podosomes in primary human macrophages
    S Linder
    Max von Pettenkofer Institut für Medizinische Mikrobiologie, Pettenkoferstrasse 9a, Ludwig Maximilians Universitat, 80336 Munich, Germany
    Proc Natl Acad Sci U S A 96:9648-53. 1999
  6. pmc Antigen receptor-induced activation and cytoskeletal rearrangement are impaired in Wiskott-Aldrich syndrome protein-deficient lymphocytes
    J Zhang
    Department of Medicine, University of Toronto, Ontario, Canada M5G 1X5
    J Exp Med 190:1329-42. 1999
  7. ncbi Mutations of the Wiskott-Aldrich Syndrome Protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation
    YinZhu Jin
    Department of Pediatrics, University of Washington, Seattle, WA 98109, USA
    Blood 104:4010-9. 2004
  8. ncbi Wiskott-Aldrich syndrome protein deficiency leads to reduced B-cell adhesion, migration, and homing, and a delayed humoral immune response
    Lisa Westerberg
    Karolinska Institutet, Department of Cell and Molecular Biology, Medical Nobel Institute, Box 285, SE 171 77 Stockholm, Sweden
    Blood 105:1144-52. 2005
  9. ncbi Cutting edge: the Wiskott-Aldrich syndrome protein is required for efficient phagocytosis of apoptotic cells
    Y Leverrier
    Ludwig Institute for Cancer Research, Royal Free and University College Medical School Branch, London, United Kingdom
    J Immunol 166:4831-4. 2001
  10. ncbi Influence of the C terminus of Wiskott-Aldrich syndrome protein (WASp) and the Arp2/3 complex on actin polymerization
    H N Higgs
    Structural Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA
    Biochemistry 38:15212-22. 1999

Detail Information

Publications230 found, 100 shown here

  1. ncbi Autoimmunity in Wiskott-Aldrich syndrome: risk factors, clinical features, and outcome in a single-center cohort of 55 patients
    Sophie Dupuis-Girod
    Unité d Immunologie et d Hématologie Pédiatriques, Hopital Necker Enfants Malades, Paris, France
    Pediatrics 111:e622-7. 2003
    ..To evaluate the occurrence of autoimmune and inflammatory complications in Wiskott-Aldrich syndrome (WAS) and to determine risk factors and the prognosis of such complications with the aim of improving the definition of treatment options...
  2. ncbi Wiskott-Aldrich syndrome protein-deficient mice reveal a role for WASP in T but not B cell activation
    S B Snapper
    Howard Hughes Medical Institute, Children s Hospital, Boston, Massachusetts 02115, USA
    Immunity 9:81-91. 1998
    ..We discuss the implications of our findings regarding WASP function in receptor signaling and cytoskeletal reorganization in T and B cells and compare the effects of WASP deficiency in mice and humans...
  3. pmc Early deficit of lymphocytes in Wiskott-Aldrich syndrome: possible role of WASP in human lymphocyte maturation
    J Y Park
    The CBR Institute for Biomedical Research, Harvard Medical School, Boston 02115, USA
    Clin Exp Immunol 136:104-10. 2004
    ....
  4. ncbi A lentiviral vector encoding the human Wiskott-Aldrich syndrome protein corrects immune and cytoskeletal defects in WASP knockout mice
    S Charrier
    Genethon UMR CNRS 8115, Evry, France
    Gene Ther 12:597-606. 2005
    ..These data support further development of such lentiviral vectors for the gene therapy of WAS...
  5. pmc Wiskott-Aldrich syndrome protein regulates podosomes in primary human macrophages
    S Linder
    Max von Pettenkofer Institut für Medizinische Mikrobiologie, Pettenkoferstrasse 9a, Ludwig Maximilians Universitat, 80336 Munich, Germany
    Proc Natl Acad Sci U S A 96:9648-53. 1999
    ..These findings indicate that WASp controls podosome assembly and, in cooperation with CDC42Hs, podosome disassembly in primary human macrophages...
  6. pmc Antigen receptor-induced activation and cytoskeletal rearrangement are impaired in Wiskott-Aldrich syndrome protein-deficient lymphocytes
    J Zhang
    Department of Medicine, University of Toronto, Ontario, Canada M5G 1X5
    J Exp Med 190:1329-42. 1999
    ..The data also reveal a role for WASp in modulating endocytosis and phagocytosis and, accordingly, suggest that the immune deficit conferred by WASp deficiency reflects the disruption of a broad range of cellular behaviors...
  7. ncbi Mutations of the Wiskott-Aldrich Syndrome Protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation
    YinZhu Jin
    Department of Pediatrics, University of Washington, Seattle, WA 98109, USA
    Blood 104:4010-9. 2004
    ..By analyzing a large number of patients with WAS/XLT at the molecular level we identified 5 mutational hotspots in the WASP gene and have been able to establish a strong association between genotype and phenotype...
  8. ncbi Wiskott-Aldrich syndrome protein deficiency leads to reduced B-cell adhesion, migration, and homing, and a delayed humoral immune response
    Lisa Westerberg
    Karolinska Institutet, Department of Cell and Molecular Biology, Medical Nobel Institute, Box 285, SE 171 77 Stockholm, Sweden
    Blood 105:1144-52. 2005
    ..In addition, the germinal center reaction was reduced in WASp-deficient mice. Thus, WASp is crucial for optimal B-cell responses and plays a pivotal role in the primary humoral immune response...
  9. ncbi Cutting edge: the Wiskott-Aldrich syndrome protein is required for efficient phagocytosis of apoptotic cells
    Y Leverrier
    Ludwig Institute for Cancer Research, Royal Free and University College Medical School Branch, London, United Kingdom
    J Immunol 166:4831-4. 2001
    ..The efficiency of apoptotic cell clearance may be a key determinant in the suppression of tissue inflammation and prevention of autoimmunity...
  10. ncbi Influence of the C terminus of Wiskott-Aldrich syndrome protein (WASp) and the Arp2/3 complex on actin polymerization
    H N Higgs
    Structural Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA
    Biochemistry 38:15212-22. 1999
    ..Preformed filaments increase the rate of nucleation by WASp WA and the Arp2/3 complex but not the number of filaments that are generated. We propose that filament side binding by the Arp2/3 complex enhances its activation by WASp WA...
  11. ncbi Two GTPases, Cdc42 and Rac, bind directly to a protein implicated in the immunodeficiency disorder Wiskott-Aldrich syndrome
    P Aspenstrom
    Department of Zoological Cell Biology, Wenner Gren Institute, Stockholm, Sweden
    Curr Biol 6:70-5. 1996
    ..In order to examine more closely the mechanisms underlying the diverse functions of Rho GTPases in mammalian cells, we searched for downstream targets of these proteins...
  12. pmc Wiskott-Aldrich syndrome protein is required for regulatory T cell homeostasis
    Stephanie Humblet-Baron
    Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington, USA
    J Clin Invest 117:407-18. 2007
    ..Finally, WASp(+) Tregs exhibited a marked selective advantage in vivo in a WAS patient with a spontaneous revertant mutation, indicating that altered Treg fitness likely explains the autoimmune features in human WAS...
  13. ncbi Impaired dendritic-cell homing in vivo in the absence of Wiskott-Aldrich syndrome protein
    Sofia de Noronha
    Molecular Immunology Unit, Institute of Child Health, London WC1N 1EH, UK
    Blood 105:1590-7. 2005
    ....
  14. ncbi X-linked thrombocytopenia and Wiskott-Aldrich syndrome are allelic diseases with mutations in the WASP gene
    A Villa
    Istituto di Tecnologie Biomediche Avanzate, CNR, Milano, Italy
    Nat Genet 9:414-7. 1995
    ..Our results demonstrate that XLT and WAS are allelic forms of the same disease, but the causes of the differences need to be further investigated...
  15. ncbi Clinical course of patients with WASP gene mutations
    Kohsuke Imai
    Department of Pediatrics and Developmental Biology, Graduate School of Medicine, Tokyo Medical and Dental University, 1 5 45, Yushima, Bunkyo ku, Tokyo, 113 8519, Japan
    Blood 103:456-64. 2004
    ..Based on data presented here, hematopoietic stem cell transplantation should be considered, especially for WASP-negative patients, while the patients are young to improve prognosis...
  16. ncbi Defective nuclear translocation of nuclear factor of activated T cells and extracellular signal-regulated kinase underlies deficient IL-2 gene expression in Wiskott-Aldrich syndrome
    Antonella Cianferoni
    Division of Immunology, Children s Hospital, Boston, MA 02115, USA
    J Allergy Clin Immunol 116:1364-71. 2005
    ..The transcription factors nuclear factor-kappaB (NF-kappaB), nuclear factor of activated T cells (NF-AT), and activating protein-1 (AP-1) play a critical role in IL-2 gene expression...
  17. ncbi Wiskott-Aldrich syndrome protein, a novel effector for the GTPase CDC42Hs, is implicated in actin polymerization
    M Symons
    Onyx Pharmaceuticals, Richmond, California 94806, USA
    Cell 84:723-34. 1996
    ..The WASP sequence contains two novel domains that are homologous to other proteins involved in action organization...
  18. ncbi Impaired T-cell priming in vivo resulting from dysfunction of WASp-deficient dendritic cells
    Gerben Bouma
    Institute of Child Health, University College London UCL, Molecular Immunology Unit, London, UK
    Blood 110:4278-84. 2007
    ....
  19. pmc WASP regulates suppressor activity of human and murine CD4(+)CD25(+)FOXP3(+) natural regulatory T cells
    Francesco Marangoni
    San Raffaele Telethon Institute for Gene Therapy HSR TIGET, 20132 Milan, Italy
    J Exp Med 204:369-80. 2007
    ..Thus, WASP appears to play an important role in the activation and suppressor function of nTreg cells, and a dysfunction or incorrect localization of nTreg cells may contribute to the development of autoimmunity in WAS patients...
  20. pmc Development of lentiviral gene therapy for Wiskott Aldrich syndrome
    Anne Galy
    Head of Immunology and Gene Therapy Group, INSERM U790, Genethon, 1 bis rue de l Internationale, 91002 Evry, France
    Expert Opin Biol Ther 8:181-90. 2008
    b>Wiskott Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency...
  21. ncbi Mutations that cause the Wiskott-Aldrich syndrome impair the interaction of Wiskott-Aldrich syndrome protein (WASP) with WASP interacting protein
    D M Stewart
    Immunophysiology Section, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 162:5019-24. 1999
    ..Point mutant analyses in the two-hybrid system and in vitro show impairment of WASP-WIP interaction with three WASP missense mutants known to cause WAS. We conclude that impaired WASP-WIP interaction may contribute to WAS...
  22. ncbi The Wiskott-Aldrich syndrome
    Hans D Ochs
    University of Washington, School of Medicine, Seattle 98195, USA
    J Allergy Clin Immunol 117:725-38; quiz 739. 2006
    ....
  23. ncbi Cutting edge: selective requirement for the Wiskott-Aldrich syndrome protein in cytokine, but not chemokine, secretion by CD4+ T cells
    Vanessa Morales-Tirado
    David H Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, and Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14642, USA
    J Immunol 173:726-30. 2004
    ..We propose that the use of different secretory pathways for cytokines and chemokines enables CD4(+) T cell activity to be further fine-tuned to serve specialized effector functions...
  24. ncbi Autoinhibition and activation mechanisms of the Wiskott-Aldrich syndrome protein
    A S Kim
    Cellular Biochemistry and Biophysics Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Nature 404:151-8. 2000
    ..These data show that 'intrinsically unstructured' peptides such as the GTPase-binding domain of WASP can be induced into distinct structural and functional states depending on context...
  25. ncbi Isolation of a novel gene mutated in Wiskott-Aldrich syndrome
    J M Derry
    Howard Hughes Medical Institute, Beckman Center for Molecular and Genetic Medicine, Stanford, California
    Cell 78:635-44. 1994
    ..WASP encodes a 501 amino acid proline-rich protein that is likely to be a key regulator of lymphocyte and platelet function...
  26. ncbi Spontaneous in vivo reversion of an inherited mutation in the Wiskott-Aldrich syndrome
    T Ariga
    Department of Human Gene Therapy and Pediatrics, Hokkaido University School of Medicine, Sapporo, Japan
    J Immunol 166:5245-9. 2001
    ..This case might have significant implications regarding the prospects of the future gene therapy for WAS patients...
  27. ncbi The Cdc42/Rac interactive binding region motif of the Wiskott Aldrich syndrome protein (WASP) is necessary but not sufficient for tight binding to Cdc42 and structure formation
    M G Rudolph
    Max Planck Institut fur molekulare Physiologie, Rheinlanddamm 201, 44139 Dortmund, Germany
    J Biol Chem 273:18067-76. 1998
    b>Wiskott Aldrich syndrome is a rare hereditary disease that affects cell morphology and signal transduction in hematopoietic cells...
  28. pmc Fyn and PTP-PEST-mediated regulation of Wiskott-Aldrich syndrome protein (WASp) tyrosine phosphorylation is required for coupling T cell antigen receptor engagement to WASp effector function and T cell activation
    Karen Badour
    Mount Sinai Hospital, 600 University Avenue, Room 656A, Toronto, Ontario M5G 1X5, Canada
    J Exp Med 199:99-112. 2004
    ....
  29. ncbi CrkL is an adapter for Wiskott-Aldrich syndrome protein and Syk
    A Oda
    Hokkaido Red Cross Blood Center, Sapporo, Japan
    Blood 97:2633-9. 2001
    ..Thus, CrkL is a novel molecular adapter for WASP and syk and may potentially transfer these molecules to the cytoskeleton through association with cytoskeletal proteins such as Hic-5...
  30. ncbi Identification of WASP mutations in patients with Wiskott-Aldrich syndrome and isolated thrombocytopenia reveals allelic heterogeneity at the WAS locus
    R Kolluri
    Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06536 0812, USA
    Hum Mol Genet 4:1119-26. 1995
    ....
  31. ncbi A novel mutation W252X in the WAS gene in a Korean patient with Wiskott-Aldrich syndrome
    Hee Jin Kim
    Department of Laboratory Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
    Int J Hematol 83:426-8. 2006
    ..756G>A; p.W252X). Family study revealed that neither of the parents had the mutation, indicating the de novo occurrence of the mutation...
  32. pmc Wiskott-Aldrich syndrome protein is required for NK cell cytotoxicity and colocalizes with actin to NK cell-activating immunologic synapses
    Jordan S Orange
    Department of Molecular and Cellular Biology, 7 Divinity Avenue, Harvard University, Cambridge, MA 02138, USA
    Proc Natl Acad Sci U S A 99:11351-6. 2002
    ..Thus, WASp has an important function in NK cells. In patients with WASp mutations, the resulting NK cell defects are likely to contribute to their disease...
  33. ncbi Defective Th1 cytokine gene transcription in CD4+ and CD8+ T cells from Wiskott-Aldrich syndrome patients
    Sara Trifari
    San Raffaele Telethon Institute for Gene Therapy, Milan, Italy
    J Immunol 177:7451-61. 2006
    ..Together, our data indicate that WASP regulates the transcriptional activation of T cells and is required specifically for Th1 cytokine production...
  34. ncbi Wiskott-Aldrich syndrome protein is necessary for efficient IgG-mediated phagocytosis
    R Lorenzi
    Department of Molecular Immunology, Institute of Child Health, London, England
    Blood 95:2943-6. 2000
    ..Results also show that, in normal macrophages, WASp itself is actively recruited to the cup, suggesting that assembly of this specialized cytoskeletal structure is dependent on its expression. (Blood. 2000;95:2943-2946)..
  35. ncbi WASp in immune-system organization and function
    Adrian J Thrasher
    Molecular Immunology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK
    Nat Rev Immunol 2:635-46. 2002
    ..Now, WASp has been shown to be intimately involved in many pathways that influence the function of the immune system. Disturbances in these systems result in the complex immunodysregulation of Wiskott-Aldrich syndrome...
  36. ncbi Cdc42, Rac1, and the Wiskott-Aldrich syndrome protein are involved in the cytoskeletal regulation of B lymphocytes
    L Westerberg
    Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
    Blood 98:1086-94. 2001
    ..Aberrations in WASP-deficient B lymphocytes, described here, provide further evidence that WAS is a cytoskeletal disease of hematopoietic cells. (Blood. 2001;98:1086-1094)..
  37. ncbi Evidence that the Wiskott-Aldrich syndrome protein may be involved in lymphoid cell signaling pathways
    G O Cory
    Institute of Child Health, University of London, United Kingdom
    J Immunol 157:3791-5. 1996
    ..In this work, we show binding of WASP to the Src homology 3 domains of Btk, Itk, Tec, Grb2, and phospholipase C-gamma, which suggests a function for WASP in lymphoid cell signaling...
  38. ncbi Efficacy of gene therapy for Wiskott-Aldrich syndrome using a WAS promoter/cDNA-containing lentiviral vector and nonlethal irradiation
    Loïc Dupré
    San Raffaele Telethon Institute for Gene Therapy HSR TIGET, 20132 Milan, Italy
    Hum Gene Ther 17:303-13. 2006
    ..The efficacy of WAS gene transfer into HSCs, using the WAS promoter-containing lentiviral vector, combined with nonlethal irradiation provides a strong rationale for the development of gene therapy for WAS patients...
  39. ncbi Wiskott-Aldrich syndrome protein is a key regulator of the phagocytic cup formation in macrophages
    Shigeru Tsuboi
    Infectious and Inflammatory Disease Center and Cell Imaging Facility, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    J Biol Chem 282:34194-203. 2007
    ....
  40. ncbi Restoration of podosomes and chemotaxis in Wiskott-Aldrich syndrome macrophages following induced expression of WASp
    Gareth E Jones
    The Randall Centre, King s College London, London SE1 1UL, UK
    Int J Biochem Cell Biol 34:806-15. 2002
    ..Expression of exogenous WAS protein (WASp) in these cells also restored normal polarised cell morphology and the ability to form podosomes...
  41. pmc Direct interaction of the Wiskott-Aldrich syndrome protein with the GTPase Cdc42
    R Kolluri
    Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 93:5615-8. 1996
    ..Taken together these data suggest that the WAS protein might function as a signal transduction adaptor downstream of Cdc42, and in affected males, the cytoskeletal abnormalities may result from a defect in Cdc42 signaling...
  42. ncbi Umbilical cord blood transplantation in Wiskott Aldrich syndrome
    Alan P Knutsen
    Division of Allergy Immunology, Department of Pediatrics, Saint Louis University Health Sciences Center and Cardinal Glennon Children s Hospital, Missouri 63110, USA
    J Pediatr 142:519-23. 2003
    To report the use of umbilical cord blood (UCB) stem cell transplantation in Wiskott Aldrich syndrome (WAS) when a matched sibling donor was unavailable.
  43. ncbi WASP and the phenotypic range associated with deficiency
    Luigi D Notarangelo
    Department of Pediatrics and Angelo Nocivelli Institute for Molecular Medicine, University of Brescia, Spedali Civili, Brescia, Italy
    Curr Opin Allergy Clin Immunol 5:485-90. 2005
    ..Advances in preclinical models of gene therapy for WAS are presented...
  44. ncbi Functional correction of T cells derived from patients with the Wiskott-Aldrich syndrome (WAS) by transduction with an oncoretroviral vector encoding the WAS protein
    T S Strom
    Division of Experimental Hematology, Department of Hematology Oncology, St Jude Children s Research Hospital, Memphis, TN, USA
    Gene Ther 10:803-9. 2003
    ..The demonstration that correction of T cell defects can be achieved by gene transfer supports continued efforts to develop gene therapy for WAS...
  45. ncbi Wiskott-Aldrich syndrome protein regulates lipid raft dynamics during immunological synapse formation
    Loïc Dupré
    San Raffaele Telethon Institute for Gene Therapy HSR TIGET, Via Olgettina 58, 20132 Milan, Italy
    Immunity 17:157-66. 2002
    ..These results demonstrate that WASP plays a central role in the movements of lipid rafts and identify a potential mechanism underlying the T cell defect affecting WAS patients...
  46. ncbi Improvement of migratory defects in a murine model of Wiskott-Aldrich syndrome gene therapy
    Michael P Blundell
    Molecular Immunology Unit, Wolfson Centre for Gene Therapy of Childhood Disease, University College London Institute of Child Health, London, UK
    Mol Ther 16:836-44. 2008
    ....
  47. ncbi Use of two unrelated umbilical cord stem cell units in stem cell transplantation for Wiskott-Aldrich syndrome
    M A Slatter
    Department of Paediatric Immunology, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, Newcastle, United Kingdom
    Pediatr Blood Cancer 47:332-4. 2006
    ..We report the case of a child with Wiskott-Aldrich syndrome who underwent cord blood stem cell transplantation with two separate cord blood units, 8 days apart...
  48. pmc Phenotypic perturbation of B cells in the Wiskott-Aldrich syndrome
    J Y Park
    The CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA
    Clin Exp Immunol 139:297-305. 2005
    ..The documentation of these phenotypic perturbations and deficit of total cells suggest that defects intrinsic to B-cells contribute to the impaired humoral immunity that characterizes this disease...
  49. pmc Wiskott-Aldrich syndrome protein physically associates with Nck through Src homology 3 domains
    O M Rivero-Lezcano
    Laboratory of Cellular Development and Oncology, National Institute of Dental Research, Bethesda, Maryland 20892 4330, USA
    Mol Cell Biol 15:5725-31. 1995
    ..The main p47nck region implicated in the association with p66WASP was found to be the carboxy-terminal SH3 domain...
  50. ncbi The Wiskott-Aldrich syndrome protein-interacting protein (WIP) binds to the adaptor protein Nck
    I M Anton
    Division, Children s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 273:20992-5. 1998
    ..We demonstrate the presence of profilin in Nck precipitates suggesting that Nck may couple extracellular signals to the cytoskeleton via its interaction with WIP and profilin...
  51. pmc WIP, a protein associated with wiskott-aldrich syndrome protein, induces actin polymerization and redistribution in lymphoid cells
    N Ramesh
    Division of Immunology, Children s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 94:14671-6. 1997
    ..These results suggest that WIP plays a role in cortical actin assembly that may be important for lymphocyte function...
  52. ncbi The Wiskott-Aldrich syndrome protein regulates nuclear translocation of NFAT2 and NF-kappa B (RelA) independently of its role in filamentous actin polymerization and actin cytoskeletal rearrangement
    Winifred Huang
    Department of Pediatrics, Memorial Sloan Kettering Cancer Center, Sloan Kettering Institute for Cancer Research, New York, NY 10021, USA
    J Immunol 174:2602-11. 2005
    ..Our results indicate that WASp independently regulates its dual functions, i.e., actin cytoskeletal remodeling and transcription in NK cells...
  53. ncbi Lentiviral vectors targeting WASp expression to hematopoietic cells, efficiently transduce and correct cells from WAS patients
    S Charrier
    INSERM, U790, Evry, France
    Gene Ther 14:415-28. 2007
    ..These vectors may have significant advantages for clinical application in terms of natural gene regulation, and reduction in the potential for adverse mutagenic events...
  54. ncbi Tyrosine phosphorylation regulates the SH3-mediated binding of the Wiskott-Aldrich syndrome protein to PSTPIP, a cytoskeletal-associated protein
    Y Wu
    Department of Molecular Oncology, Genentech, Inc, South San Francisco, California 94080, USA
    J Biol Chem 273:5765-70. 1998
    ..These data suggest that the PSTPIP and WASP interaction is regulated by tyrosine phosphorylation of the PSTPIP SH3 domain, and this binding event may control aspects of the actin cytoskeleton...
  55. ncbi Constitutively activating mutation in WASP causes X-linked severe congenital neutropenia
    K Devriendt
    Centre for Human Genetics, University Hospital Leuven, Leuven, Belgium
    Nat Genet 27:313-7. 2001
    ..Our findings highlight the importance of precise regulation of WASP in hematopoietic development and function, as impairment versus enhancement of its activity give rise to distinct spectra of cellular defects and clinical phenotypes...
  56. pmc SCAR, a WASP-related protein, isolated as a suppressor of receptor defects in late Dictyostelium development
    J E Bear
    Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322 3030, USA
    J Cell Biol 142:1325-35. 1998
    ..These data suggest that SCAR may be a conserved negative regulator of G protein-coupled signaling, and that it plays an important role in regulating the actin cytoskeleton...
  57. ncbi Two novel mutations of Wiskott-Aldrich syndrome: the molecular prediction of interaction between the mutated WASP L101P with WASP-interacting protein by molecular modeling
    Moon Kyu Kim
    Department of Pediatrics, Yonsei University College of Medicine, 134 Shinchon Dong Seodaemoon Gu, Seoul 120 752, South Korea
    Biochim Biophys Acta 1690:134-40. 2004
    ..A possible model for the molecular pathogenesis of WAS has been proposed by analyzing the interactions of WASP and WIP using a molecular modeling study...
  58. pmc Second-site mutation in the Wiskott-Aldrich syndrome (WAS) protein gene causes somatic mosaicism in two WAS siblings
    Taizo Wada
    Genetics and Molecular Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 4442, USA
    J Clin Invest 111:1389-97. 2003
    ..These findings strongly suggest that slipped mispairing was the cause of this second-site mutation and that selective accumulation of WASP-expressing T lymphocytes led to revertant mosaicism in these patients...
  59. ncbi Mechanism of recruitment of WASP to the immunological synapse and of its activation following TCR ligation
    Yoji Sasahara
    Division of Immunology, Children s Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 10:1269-81. 2002
    ..These results suggest that the ZAP-70-CrkL-WIP pathway and PKCtheta link TCR to WASP activation...
  60. ncbi The Wiskott-Aldrich syndrome protein acts downstream of CD2 and the CD2AP and PSTPIP1 adaptors to promote formation of the immunological synapse
    Karen Badour
    Department of Medical Genetics and Microbiology, University of Toronto, 600 University Avenue, Toronto, M5G 1X5 Ontario, Canada
    Immunity 18:141-54. 2003
    ....
  61. ncbi Lentiviral vectors transcriptionally targeted to hematopoietic cells by WASP gene proximal promoter sequences
    F Martin
    IPB López Neyra CSIC, Granada, Spain
    Gene Ther 12:715-23. 2005
    ..Therefore, lentiviral vectors incorporating proximal promoter sequences from the WASP gene confer hematopoietic-specific, and physiological protein expression...
  62. ncbi Outcome in patients with Wiskott-Aldrich syndrome following stem cell transplantation: an analysis of 57 patients in Japan
    Ryoji Kobayashi
    Department of Paediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan
    Br J Haematol 135:362-6. 2006
    ..Given the improved outcome for WAS patients following transplantation from an unrelated donor, we conclude that patients with WAS should receive SCT as soon as possible after diagnosis...
  63. ncbi Toca-1 mediates Cdc42-dependent actin nucleation by activating the N-WASP-WIP complex
    Hsin Yi Henry Ho
    Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell 118:203-16. 2004
    ..These findings represent a significantly revised view of Cdc42-signaling and shed light on the pathogenesis of Wiskott-Aldrich syndrome...
  64. ncbi Impaired natural and CD16-mediated NK cell cytotoxicity in patients with WAS and XLT: ability of IL-2 to correct NK cell functional defect
    Angela Gismondi
    University La Sapienza, Viale Regina Elena, 324, 00161 Rome, Italy
    Blood 104:436-43. 2004
    ..We also found that WASp undergoes tyrosine phosphorylation upon CD16 or beta2-integrin engagement on NK cells...
  65. ncbi Genotype-proteotype linkage in the Wiskott-Aldrich syndrome
    Maxim I Lutskiy
    CBR Institute for Biomedical Research, and Department of Pediatrics, Harvard Medical School, 800 Huntington Avenue, Boston, MA 02115, USA
    J Immunol 175:1329-36. 2005
    ..Knowledge of the molecular effect of mutations would aid also in identifying disease-modifying genes...
  66. pmc Analysis of T-cell repertoire diversity in Wiskott-Aldrich syndrome
    Taizo Wada
    Genetics and Molecular Biology Branch, National Human Genome Research Institute NHGRI, National Institutes of Health NIH, 49 Convent Dr, Bldg 49, Rm 3A20, MSC 4442, Bethesda, MD 20892 4442, USA
    Blood 106:3895-7. 2005
    ..These findings suggest that WASP deficiency does not limit thymic generation of a normal TCR and indicate that T-cell oligoclonality may contribute to the immunodeficiency in older patients with WAS...
  67. pmc Mosaicism of NK cells in a patient with Wiskott-Aldrich syndrome
    Maxim I Lutskiy
    The CBR Institute for Biomedical Research, Inc, Boston, MA 02115, USA
    Blood 106:2815-7. 2005
    ..The importance of reconstituting the NK-cell lineage is discussed...
  68. ncbi WASP (Wiskott-Aldrich syndrome protein) gene mutations and phenotype
    Kohsuke Imai
    INSERM The French Institute of Health and Medical Research U429, Hopital Necker Enfants Malades, Paris, France
    Curr Opin Allergy Clin Immunol 3:427-36. 2003
    ..In this review we will focus on recent molecular findings that provide a better understanding of the pathogenesis of this complex disease and explore the correlation of genotype and clinical phenotype...
  69. ncbi Novel membrane cell projection defects in Wiskott-Aldrich syndrome B cells
    Nuria Andreu
    Programa Gens i Malaltia, Centre de Regulació Genòmica CRG UPF, Parc de Recerca Biomèdica PRBB, 08003 Barcelona, Spain
    Int J Mol Med 20:445-50. 2007
    ..Such alterations most probably result from a WASP dysfunction, given that a retroviral gene transfer of a corrected form of the WASP gene was able to rescue the abnormal phenotypes...
  70. ncbi Structure and function of the Wiskott-Aldrich syndrome protein
    Hans D Ochs
    Departments of Pediatrics, University of Washington, Seattle, Washington 98109, USA
    Curr Opin Hematol 12:284-91. 2005
    ..The responsible gene, WASP, has multiple domains, each with unique functions that were only recently fully recognized...
  71. ncbi Malignant B cell non-Hodgkin's lymphoma of the larynx in children with Wiskott Aldrich syndrome
    G Palenzuela
    Service d Oncologie Pediatrique, Hopital Arnaud de Villeneuve, CHU Montpellier, 34295 Montpellier Cedex 5, France
    Int J Pediatr Otorhinolaryngol 67:989-93. 2003
    A 15 years old male with a primary diagnosis of Wiskott Aldrich syndrome presented a laryngeal B cell lymphoma associated with Epstein-Barr virus...
  72. ncbi Mutational analysis of the WASP gene in 2 Korean families with Wiskott-Aldrich syndrome
    Eun Kyeong Jo
    Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, Korea
    Int J Hematol 78:40-4. 2003
    ..To our knowledge, this is the first report on molecular diagnosis of WAS in Korea. In addition, we detected normal WASP expression in lymphocytes from carrier mothers, a finding consistent with the data on skewed X inactivation...
  73. ncbi SLP-76 coordinates Nck-dependent Wiskott-Aldrich syndrome protein recruitment with Vav-1/Cdc42-dependent Wiskott-Aldrich syndrome protein activation at the T cell-APC contact site
    Rong Zeng
    Department of Pathology, University of Chicago, Chicago, IL 60637, USA
    J Immunol 171:1360-8. 2003
    ..Taken together, these findings reconstruct the signaling pathway leading from TCR ligation to localized WASP activation...
  74. pmc Efficient antigen presentation of soluble, but not particulate, antigen in the absence of Wiskott-Aldrich syndrome protein
    Lisa Westerberg
    Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
    Immunology 109:384-91. 2003
    ..In conclusion, our data suggest that WASP is not needed for processing and presentation of soluble antigen, but that efficient presentation of particulate antigen require WASP...
  75. ncbi Improved lentiviral vectors for Wiskott-Aldrich syndrome gene therapy mimic endogenous expression profiles throughout haematopoiesis
    C Frecha
    Immunology and Cell Biology Department, Institute of Parasitology and Biomedicine López Neyra CSIC, Parque Tecnologico Ciencias de la Salud, Granada, Spain
    Gene Ther 15:930-41. 2008
    ..This emphasizes that it is a suitable LV backbone for gene therapy of haematopoietic diseases such as WAS...
  76. pmc Somatic mosaicism in Wiskott--Aldrich syndrome suggests in vivo reversion by a DNA slippage mechanism
    T Wada
    Disorders of Immunity Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 98:8697-702. 2001
    ....
  77. pmc Bee1, a yeast protein with homology to Wiscott-Aldrich syndrome protein, is critical for the assembly of cortical actin cytoskeleton
    R Li
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    J Cell Biol 136:649-58. 1997
    ..Thus, Bee1 protein may be a crucial component of a cytoskeletal complex that controls the assembly and organization of actin filaments at the cell cortex...
  78. ncbi Non-myeloablative bone marrow transplantation in an adult with Wiskott-Aldrich syndrome
    Hilary J Longhurst
    Department of Immunopathology, St Bartholomew s Hospital, London, UK
    Br J Haematol 116:497-9. 2002
    ..We describe a non-myeloablative transplant of a 26-year-old man with WAS, undertaken because of severe infections and vasculitis. Partial engraftment and immunorestoration were achieved. The patient is well 1 year post transplantation...
  79. ncbi Variable expression of WASP in B cell lines of Wiskott-Aldrich syndrome patients
    E REMOLD-O'DONNELL
    Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 158:4021-5. 1997
    ..The findings suggest that the clinical variability of the WAS can partially be explained by the level of WASP protein in the patient's cells...
  80. ncbi Monocytes from Wiskott-Aldrich patients display reduced chemotaxis and lack of cell polarization in response to monocyte chemoattractant protein-1 and formyl-methionyl-leucyl-phenylalanine
    R Badolato
    Clinica Pediatrica, Universita di Brescia, Italy
    J Immunol 161:1026-33. 1998
    ..These results suggest that WAS protein is involved in the monocyte response to the chemokines MCP-1 and macrophage inflammatory protein-1alpha...
  81. ncbi Defects in T-cell-mediated immunity to influenza virus in murine Wiskott-Aldrich syndrome are corrected by oncoretroviral vector-mediated gene transfer into repopulating hematopoietic cells
    Ted S Strom
    Division of Experimental Hematology, Department of Hematology Oncology, St Jude Children s Research Hospital, 332 N Lauderdale, Memphis, TN 38105, USA
    Blood 102:3108-16. 2003
    ..The defective secondary T-cell response to influenza virus was also improved in gene-corrected animals...
  82. ncbi Global disruption of the WASP autoinhibited structure on Cdc42 binding. Ligand displacement as a novel method for monitoring amide hydrogen exchange
    M Buck
    Howard Hughes Medical Institute, Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA
    Biochemistry 40:14115-22. 2001
    ..This notion is consistent with the requirement of multiple input signals in order to achieve maximal activation in many effector molecules...
  83. ncbi Cdc42-interacting protein 4 mediates binding of the Wiskott-Aldrich syndrome protein to microtubules
    L Tian
    Metabolism Branch, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 275:7854-61. 2000
    ..We conclude that CIP4 can mediate the association of WASP with microtubules. This may facilitate transport of WASP to sites of substrate adhesion in hematopoietic cells...
  84. ncbi Defective actin polymerization in EBV-transformed B-cell lines from patients with the Wiskott-Aldrich syndrome
    F Facchetti
    Department of Pathology, University of Brescia, Italy
    J Pathol 185:99-107. 1998
    ..As a whole, the degree of impairment of WASP protein expression in WAS/XLT seems to correlate with anomalies of cytoskeletal organization, strongly supporting a role for WASP in the regulation of F-actin polymerization...
  85. ncbi The WASp homologue Las17p functions with the WIP homologue End5p/verprolin and is essential for endocytosis in yeast
    S N Naqvi
    Institute of Molecular Agrobiology, National University of Singapore, Republic of Singapore
    Curr Biol 8:959-62. 1998
    ..As las17 delta deletion mutants are blocked in endocytosis, we conclude that Las17p and End5p interact and are essential for endocytosis...
  86. ncbi Impact of donor type on outcome of bone marrow transplantation for Wiskott-Aldrich syndrome: collaborative study of the International Bone Marrow Transplant Registry and the National Marrow Donor Program
    A H Filipovich
    Statistical Center of the International Bone Marrow Transplant Registry, Health Policy Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA
    Blood 97:1598-603. 2001
    ..The best transplantation outcomes in Wiskott-Aldrich syndrome are achieved with HLA-identical sibling donors. Equivalent survivals are possible with unrelated donors in young children...
  87. pmc Identification of mutations in the Wiskott-Aldrich syndrome gene and characterization of a polymorphic dinucleotide repeat at DXS6940, adjacent to the disease gene
    S P Kwan
    Department of Immunology, Rush Medical School, Chicago, IL 60612, USA
    Proc Natl Acad Sci U S A 92:4706-10. 1995
    ....
  88. ncbi Wiskott-Aldrich syndrome in a female
    Maxim I Lutskiy
    Center for Blood Research, and the Division of Immunology, Children s Hospital, and the Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
    Blood 100:2763-8. 2002
    ....
  89. ncbi A novel protocol to identify mutations in patients with wiskott-Aldrich syndrome
    L N Jones
    Center for Blood Research, Boston, Massachusetts 02115, USA
    Blood Cells Mol Dis 28:392-8. 2002
    ..This cumulative experience demonstrates the suitability, reliability, and versatility of the new protocol...
  90. ncbi Gene therapy for Wiskott-Aldrich syndrome: rescue of T-cell signaling and amelioration of colitis upon transplantation of retrovirally transduced hematopoietic stem cells in mice
    Christoph Klein
    Division of Molecular Medicine and Pediatric Hematology Oncology, Howard Hughes Medical Institute, The Children s Hospital, Boston, MA, USA
    Blood 101:2159-66. 2003
    ..Our results provide proof of principle that the WAS-associated T-cell signaling defects can be improved upon transplantation of retrovirally transduced HSCs without overt toxicity and may encourage clinical gene therapy trials...
  91. ncbi Novel mutations, no detectable mRNA and familial genetic analysis of the Wiskott-Aldrich syndrome protein gene in six Japanese patients with Wiskott-Aldrich syndrome
    Y Sasahara
    Department of Paediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan
    Eur J Pediatr 159:23-30. 2000
    ..Conclusion Genetic and protein analysis is useful in the definite diagnosis and follow up of Wiskott-Aldrich syndrome patients and in carrier detection, especially of atypical or sporadic patients...
  92. ncbi Retrovirus-mediated WASP gene transfer corrects Wiskott-Aldrich syndrome T-cell dysfunction
    Taizo Wada
    Disorders of Immunity Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, 10 Center Drive, Building 10, Room 10C103, Bethesda, MD 20892 1851, USA
    Hum Gene Ther 13:1039-46. 2002
    ..These findings suggest that biologic defects of WAS T cells can be corrected in vitro by retrovirus-mediated gene transfer and pose the basis for future investigation of gene therapy as treatment for WAS...
  93. ncbi Mixed chimera status of 12 patients with Wiskott-Aldrich syndrome (WAS) after hematopoietic stem cell transplantation: evaluation by flow cytometric analysis of intracellular WAS protein expression
    Koji Yamaguchi
    Research Group of Human Gene Therapy, the Division of Cancer Medicine, Department of Surgical Oncology, Hokkaido University, Graduate School of Medicine, Sapporo, Japan
    Blood 100:1208-14. 2002
    ..We conclude that FCM-WASP is a potentially useful method for clinical follow-up of WAS patients who have undergone HST. Our findings may also have important implications for the role of WASP during hematopoietic development...
  94. ncbi GRB2 links signaling to actin assembly by enhancing interaction of neural Wiskott-Aldrich syndrome protein (N-WASp) with actin-related protein (ARP2/3) complex
    M F Carlier
    Dynamique du Cytosquelette, Cristallographie et RMN Biologiques, Laboratoire d Enzymologie et Biochimie Structurale, CNRS 91198 Gif sur Yvette, Paris, France Pasteur
    J Biol Chem 275:21946-52. 2000
    ..These results suggest that Grb2 may activate Arp2/3 complex-mediated actin polymerization downstream from the receptor tyrosine kinase signaling pathway...
  95. pmc Wiskott-Aldrich syndrome: another piece in the puzzle
    L D Notarangelo
    Clin Exp Immunol 139:173-5. 2005
  96. ncbi Recurrent V75M mutation within the Wiskott-Aldrich syndrome protein: description of a homozygous female patient
    Alexis Proust
    Service d Hematologie, d Immunologie et de Cytogénétique, Hopital de Bicetre, AP HP, Faculte de Medecine Paris Sud, 78 rue du General Leclerc, 94275 Le Kremlin Bicetre, France
    Eur J Haematol 75:54-9. 2005
    ..Its amount was about 10% and 15% of normal in platelets and mononucleated white cells, respectively. In all patients was the picture consistent with XLT...
  97. ncbi Protein assays for diagnosis of Wiskott-Aldrich syndrome and X-linked thrombocytopenia
    W Qasim
    Molecular Immunology Unit, Institute of Child Health, University College London, UK
    Br J Haematol 113:861-5. 2001
    ..In all cases, subsequent genetic analysis confirmed the presence of a WASp gene mutation. We believe that protein-based assays should be employed as the first line of investigation in the diagnosis of WAS spectrum disorders...
  98. ncbi Macrophages of patients with X-linked thrombocytopenia display an attenuated Wiskott-Aldrich syndrome phenotype
    Stefan Linder
    Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Ludwig Maximilians Universitat, Dr von Haunersches Kinderspital, Klinikum Innenstadt, Lindwurmstr, Munchen, Germany
    Immunol Cell Biol 81:130-6. 2003
    ..Further evaluation of this and other, as yet unrecognized, cellular defects may provide a more complete picture of the continuum of Wiskott-Aldrich syndrome and X-linked thrombocytopenia defects...
  99. ncbi A role for Wiskott-Aldrich syndrome protein in T-cell receptor-mediated transcriptional activation independent of actin polymerization
    C Silvin
    Onyx Pharmaceuticals, Richmond, California 94806, USA
    J Biol Chem 276:21450-7. 2001
    ..Our results suggest that WASP activates transcription following TCR stimulation in a manner that is independent of its role in Arp2/3-directed actin polymerization...
  100. ncbi Molecular diagnosis of Wiskott-Aldrich syndrome in Taiwan
    Yin Hsiu Chien
    Department of Pediatrics, National Taiwan University Hospital and National Taiwan University, Taipei, Taiwan, ROC
    J Microbiol Immunol Infect 37:276-81. 2004
    ..The use of a multidisciplinary approach including DNA and protein analysis is required for molecular diagnosis and genetic counseling of WAS...
  101. ncbi Lentiviral vector-mediated gene transfer in T cells from Wiskott-Aldrich syndrome patients leads to functional correction
    Loïc Dupré
    San Raffaele Telethon Institute for Gene Therapy, 20132 Milan, Italy
    Mol Ther 10:903-15. 2004
    ..The observation that lentiviral vector-mediated gene transfer results in correction of T cell defects in vitro supports their application for gene therapy in WAS patients...

Research Grants62

  1. Identifying Key Structural Elements in the Activation of the Arp2/3 Complex
    Patricia A Khuu; Fiscal Year: 2013
    ..Arp2/3 is also involved in metastasis as it is required in the formation of cellular structures such as lamellipodia of migrating cells and invadopodia of cancers cells [5, 6]. ..
  2. Pososome Regulated Monocyte/Macrophage Tissue Infiltration
    Dianne Cox; Fiscal Year: 2013
    ....
  3. Primary Immune Deficiency Treatment Consortium Annual Scientific Meeting
    Luigi Daniele Notarangelo; Fiscal Year: 2013
    ..Interaction with Patient Advocacy Groups will promote synergy in PID awareness campaigns. ..
  4. Determination of a Mechanism for the Thrombocytopenia of WAS
    Ted S Strom; Fiscal Year: 2010
    ..If our hypothesis is correct, these studies will demonstrate a firm link between the thrombocytopenia of WAS and a much more common (and poorly understood) condition, immune thrombocytopenic purpura. ..
  5. Impaired integrin-dependent function of WASP-deficient platelets
    EILEEN REMOLD-O'DONNELL; Fiscal Year: 2010
    ..The goal of this project is to identify the normal function of WASP in platelets and the cause of platelet loss in Wiskott-Aldrich patients. ..
  6. Training program in hematologic and oncologic diseases
    Yi Zheng; Fiscal Year: 2012
    ..The progress of each trainee will be reviewed and evaluated semi- annually. ..
  7. STAT3 Functional Defects and a Novel Therapeutic Approach for Hyper IgE Syndrome
    Hans Ochs; Fiscal Year: 2009
    ..Results from these investigations will clarify the function of WASP, explain the phenotypes of WAS/XLT and will undoubtedly have implications for optimal therapy of affected patients. ..
  8. Cytoskeletal regulation of intestinal barrier function and response to pathogens
    John Garber; Fiscal Year: 2013
    ..At the conclusion of the award period, the candidate will be well positioned for a career as an independent, R01-funded investigator. ..
  9. Understanding the Role of N-WASP in the Intestinal Epithelium
    John Garber; Fiscal Year: 2010
    ..PUBLIC HEALTH RELEVANCE: The overall goal of this proposal is to further our understanding of the mechanism(s) that regulate intestinal epithelial structure and enable it to perform its barrier function in both health and disease ..
  10. Innate vs Adaptive Contributions to Th2 Pathology in Wiskott Aldrich Syndrome
    Deborah J Fowell; Fiscal Year: 2012
    ..For retention within the tissue we will use intravital 2-photon microscopy to assess interstitial motility and T-APC contact time and use adoptive transfer into the dermal site to follow tissue retention/exit. ..
  11. Exploring Regulatory T Cell Dysfunction in a Murine Model of Colitis
    Scott B Snapper; Fiscal Year: 2013
    ..this proposal is to further our understanding of the regulatory T cell defects and the mechanism of colitis in Wiskott Aldrich Syndrome protein knock-out mice and to take advantage of a model of colitis that also has a human correlate.
  12. Live Cell Interferometry for Quantifying Mass Transport in Cancer
    THOMAS ZANGLE; Fiscal Year: 2013
    ..abstract_text> ..
  13. Primary Immune Deficiency Treatment Consortium
    Morton Cowan; Fiscal Year: 2013
    ..These studies will resolve critical questions concerning HCT for these disorders and form the basis for future prospective clinical trials. ..
  14. The F-BAR protein CIP4 in WAS-dependent thrombocytopenia
    SETH JOEL COREY; Fiscal Year: 2012
    ..We will use these unique mice strains to measure platelet survival and to correlate with altered immune function. ..
  15. Lentiviral Gene Therapy for Wiskott-Aldrich Syndrome
    David J Rawlings; Fiscal Year: 2012
    ..Our proposed studies will provide nearly all of the key expression, efficacy, and safety data required to move forward with a human gene therapy trial for WAS;and have a very high likelihood for translation into new therapies. ..
  16. Phase 1 Study of Interleukin-2 in Wiskott-Aldrich Syndrome
    Soma Jyonouchi; Fiscal Year: 2013
    ....
  17. Regulation of Membrane-Cortical Cytoskeleton Crosstalk by WASH
    Susan M Parkhurst; Fiscal Year: 2013
    ..The Wiskott Aldrich Syndrome (WAS) protein family, which act as effectors of Rho family GTPases, polymerize actin through the Arp2/3 ..
  18. Structural Study of GTPase Regulators and Effectors
    Michael K Rosen; Fiscal Year: 2013
    ..This work will suggest general mechanisms by which multivalent interactions can be used to control the specificity and timing of membrane interactions of soluble species. ..
  19. Somatic Mosaicism in the Wiskott-Aldrich Syndrome
    Brian R Davis; Fiscal Year: 2010
    ..Public Health Relevance: This exploratory study seeks to identify critical events in the development of somatic mosaicism in patients with inherited genetic disease - in particular, the Wiskott-Aldrich Syndrome. ..
  20. Regulation of Actin Dynamics During T Cell Activation
    Daniel D Billadeau; Fiscal Year: 2013
    ..The experiments in this proposal are aimed at understanding the role of the novel actin regulatory protein WASH in T cell activation and thymocyte selection. ..
  21. Deciphering How Aberrant Innate Immune Cells Induce Colitis
    Deanna D Nguyen; Fiscal Year: 2013
    ..The broader aim is to make a meaningful contribution to the field of mucosal immunology in the hope of someday finding more effective and less toxic treatments for IBD. ..
  22. Specificity of Effector Activation by Rho Family GTPases
    Jeffrey R Peterson; Fiscal Year: 2012
    ..This proposal will illuminate how this coordination could be corrupted in disease and will provide crucial information for the selection of optimal drug targets for new therapeutic approaches. ..
  23. Epigenetic Regulation by WASP of Human TBX21 Gene Transcription Program
    Yatin M Vyas; Fiscal Year: 2013
    ....
  24. Molecular Pathogenesis of Immune Dysfunction In Wiskott-Aldrich-Syndrome
    Yatin M Vyas; Fiscal Year: 2012
    ..These studies should lay the foundation for designing novel therapies in the future, for this life-threatening, debilitating disease of the childhood. ..
  25. SIGNALING AND CYTOSKELETAL ORGANIZATION IN BLOOD CELLS
    RAIF SALIM GEHA; Fiscal Year: 2012
    ..Core A will administer the program. Core B will provide genetically engineered mice and generate monoclonal antibodies for all four projects. ..
  26. HUMAN BLOOD PLATELET GLYCOPROTEIN IB
    Alan Michelson; Fiscal Year: 1991
    ....
  27. UMBILICAL CORD BLOOD TRANSPLANTATION
    Hal Broxmeyer; Fiscal Year: 1993
    ..Other disorders including aplastic anemia, Wiskott Aldrich syndrome and an x-linked lymphoproliferative disorder have also been transplanted with HLA-matched sibling cord ..
  28. LYMPHOCYTE GPL115--STRUCTURE-FUNCTION-DEFECT
    EILEEN REMOLD O DONNELL; Fiscal Year: 1990
    ..The hypothesized function of gpL115 in controlling senescence will also be tested by quantifying IgG molecules bound to the surface of normal lymphocytes, sialidase- treated lymphocytes and WAS lymphocytes...
  29. CELLULAR DEFECTS IN THE WISKOTT/ALDRICH SYNDROME
    EILEEN REMOLD O DONNELL; Fiscal Year: 2001
    ....
  30. PROTEIN INTERACTIONS REGULATING CELL MOTILITY
    Wendell Lim; Fiscal Year: 2009
    ....
  31. EPICS XL-MCL FLOW CYTOMETRY SYSTEM
    Fred Rosen; Fiscal Year: 2000
    ..abstract_text> ..
  32. GENETIC ANALYSIS OF IMMUNODEFICIENCY DISEASES
    Jennifer Puck; Fiscal Year: 1992
    ..common forms of severe combined immunodeficiency disease (XSCID) and agammaglobulemia (XLA), as well as Wiskott Aldrich syndrome (WA), X linked lymphoproliferative syndrome (XLP), and hyper- IgM syndrome...
  33. Shigella IcsA Activation of Actin Assembly by N-WASP
    NOEL SAUER; Fiscal Year: 2004
    ..These studies will provide insight into both the molecular mechanisms of Shigella pathogenesis and the molecular mechanisms of 0dc42-mediated actin assembly. ..
  34. MOLECULAR AND GENETIC ANALYSIS OF A BLOOD CELL DISEASE
    Scott Snapper; Fiscal Year: 2001
    ..Daniel Podolsky from the Gastrointestinal Unit at the Massachusetts General Hospital, both at Harvard Medical School. (End of Abstract) ..
  35. Genetic Analysis of the Sonic Hedgehog Target Gene BEG4
    Christopher Callahan; Fiscal Year: 2005
    ..The proposed research fellowship will yield new insights into the pathogenesis of BCCs and other Shh pathway-related malignancies and may lead to the identification of new targets for prevention and therapy. ..
  36. High Throughput Screening Assay of Cdc42 Activation in Cancer
    Louis Hodgson; Fiscal Year: 2009
    ..shown to directly affect metastatic migration of primary tumors via signaling through a sub- class of Wiskott Aldrich Syndrome protein neural-WASP (N-WASP) to initiate invadopodial protrusions exhibiting potent matrix degrading ..
  37. Structure and regulation of synaptic architecture
    AVITAL RODAL; Fiscal Year: 2009
    ..Therefore, elucidation of the conserved subcellular trafficking pathways and structures regulated by NWK will help interpret human diseases and provide new targets for therapies. ..
  38. DELINEATION OF THE WASP AND CDC42HS PATHWAY IN T CELLS
    Arie Abo; Fiscal Year: 2002
    ..Delineation of this pathway will contribute to our understanding of how cytoskeletal events are integrated with transcriptional activation and will help to understand an important genetic human disease. ..
  39. Natural Killer Cell Immune Synapse
    Bo Dupont; Fiscal Year: 2005
    ..We expect these studies to provide new insight on how NK cells interact with target cells and how MHC class I molecules regulate these processes. ..
  40. Structural Biology of Presynaptic Scaffolds
    Vinzenz Unger; Fiscal Year: 2009
    ....
  41. REACTIONS AND METABOLISM OF IMMUNE PROTEINS AND CELLS
    Fred Rosen; Fiscal Year: 1990
    ..The surface antigens of T cells of mice and man that are involved in lymphocyte toxicity will be defined by monoclonal antibodies. Control of Ia expression on murine and human macrophages will be investigated...
  42. MODELS OF HUMAN IMMUNODEFICIENCIES
    CORNELIS TERHORST; Fiscal Year: 2007
    ..Cox Terhorst - The Role of the XLP Gene, SAP, in T and B Cell Functions. Raif Geha - Mechanism of WASP Function in T cell Responses Fred AIt - Murine models of Severe Combined Immunodeficiencies. ..
  43. ROLES OF N TERMINUS OF WISKOTT ALDRICH SYNDROME PROTEIN
    Shigeru Tsuboi; Fiscal Year: 2001
    ..2) To determine whether CIB and WASP interact in MEG-Ol human megakaryoblastic cells and such interaction is required for cytoskeletal organization, integrin function, and megakaryocyte differentiation. ..
  44. THE ROLE OF NUCLEAR WASP IN THE TRANSCRIPTIONAL REGULATION OF TH1 DIFFERENTIATION
    Yatin Vyas; Fiscal Year: 2009
    ..These studies should lay the foundation for designing novel therapies in the future, for this life-threatening, debilitating disease of the childhood. ..
  45. Lentiviral Gene Therapy for Wiskott-Aldrich Syndrome
    David Rawlings; Fiscal Year: 2007
    ..abstract_text> ..
  46. Immunofluorescent 3D-analysis of NK-target conjugates
    Yatin Vyas; Fiscal Year: 2006
    ..Such analysis will improve our understanding of the biology of cytolytic effector lymphocytes that could be of potential use in immunotherapy. ..
  47. Regulation of cytoskeletal activation in NK cells
    Jordan Orange; Fiscal Year: 2006
    ..Ultimately, the candidate plans to use his position as a pediatric immunologist to better understand NK cell function and the role NK cells play in maintenance of human health. ..
  48. GENETIC STUDIES OF COWDENS SYNDROME
    MONICA PEACOCKE; Fiscal Year: 1999
    ..The experiments outlined in this proposal will provide a molecular framework for a more effective understanding of the molecular pathology of Cowden's disease. ..
  49. PHYSIOLOGICAL CHEMISTRY OF INTEGRIN FUNCTION
    Michael Dustin; Fiscal Year: 2007
    ..In Aim 3 we will determine how defects in the cytoskeleton regulators Wiskott Aldrich Syndrome protein (WASP) and WASP interacting protein (WIP) influence the lateral mobility of LFA-1 and its ability ..
  50. Membrane Movement Powered by Actin Assembly
    Jack Taunton; Fiscal Year: 2006
    ..membrane surface? (2) How does a symmetrical membrane surface assemble a polarized actin network capable of generating force? (3) How is cytosolic, GDP-bound Cdc42 converted into its membrane-associated, GTP-bound state? ..
  51. EPIDEMIOLOGY OF CANCER IN IMMUNODEFICIENCY FAMILIES
    John Kersey; Fiscal Year: 1980
    ....
  52. Differential Actin Regulation in Zebrafish Development
    David Daggett; Fiscal Year: 2006
    ..An understanding of actin regulation during vertebrate development in the zebrafish may thus provide insights into the causes and treatment of certain human diseases. ..
  53. CYTOKINES IN GENETIC AND ACQUIRED HEMOPOIETIC DISORDERS
    RICHARD O REILLY; Fiscal Year: 1993
    ..host disease in patients with: a) variants of SCID exhibiting graft resistance; b) Other diseases associated with a lethal combined immunodeficiency, and c) Wiskott-Aldrich syndrome, who lack an HLA-identical donor..
  54. MARROW TRANSPLANT/SCID/LETHAL CONGENITAL IMMUNODEFIENCY
    RICHARD O REILLY; Fiscal Year: 1990
    ..host disease in patients with: a) variants of SCID exhibiting graft resistance; b) Other diseases associated with a lethal combined immunodeficiency, and c) Wiskott-Aldrich syndrome, who lack an HLA-identical donor..
  55. Roles of the WASP N-terminus in hematopoietic cells
    Shigeru Tsuboi; Fiscal Year: 2006
    ..in hematopoietic cells will provide important information about critical biological processes such as cell migration, and it should facilitate the development of potential therapeutic agent to treat XLT and WAS ..
  56. Exploring Regulatory T Cell Dysfunction in a Murine Model of Colitis
    Scott Snapper; Fiscal Year: 2008
    ..abstract_text> ..
  57. Cytoskeletal-Pathogen Interactions in Shigella Infection
    Scott Snapper; Fiscal Year: 2007
    ..abstract_text> ..
  58. Defects of Thymic Output in Wiskott-Aldrich Syndrome
    EILEEN REMOLD O DONNELL; Fiscal Year: 2006
    ....
  59. PRENATAL STRATEGIES FOR TREATMENT OF HEMOGLOBINOPATHIES
    Alan Flake; Fiscal Year: 2002
    ..abstract_text> ..