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    Ribosomal DNA status inferred from DNA cloud assays and mass spectrometry identification of agarose-squeezed proteins interacting with chromatin (ASPIC-MS).
    Oncotarget 2017 Feb 15. Epub 2017 Feb 15.
    Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Laboratory of Mutagenesis and DNA Repair, Warsaw, 02-106, Poland.
    Ribosomal RNA-encoding genes (rDNA) are the most abundant genes in eukaryotic genomes. To meet the high demand for rRNA, rDNA genes are present in multiple tandem repeats clustered on a single or several chromosomes and are vastly transcribed. To facilitate intensive transcription and prevent rDNA destabilization, the rDNA-encoding portion of the chromosome is confined in the nucleolus. Read More

    Inherited Thrombocytopenia with a Different Type of Gene Mutation: A Brief Literature Review and Two Case Studies.
    Iran J Pediatr 2016 Oct 18;26(5):e4105. Epub 2016 Jul 18.
    Pediatric Hematologist-Oncologist, Congenital Hematological Disorders Research Center, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
    Hereditary thrombocytopenias are rare bleeding disorders, which cause a deficiency of platelets in early infancy. This group of disorders is sometimes associated with abnormal phenotypes, like absence of radius. Diagnosis of this type of thrombocytopenia is usually difficult; other causes of thrombocytopenia, such as immune disorders and infections, must be ruled out. Read More

    Skap2 is required for β2 integrin-mediated neutrophil recruitment and functions.
    J Exp Med 2017 Feb 9. Epub 2017 Feb 9.
    Department of Anesthesiology, Intensive Care, and Pain Medicine, University of Münster, 48149 Münster, Germany
    Integrin activation is required for neutrophil functions. Impaired integrin activation on neutrophils is the hallmark of leukocyte adhesion deficiency (LAD) syndrome in humans, characterized by impaired leukocyte recruitment and recurrent infections. The Src kinase-associated phosphoprotein 2 (Skap2) is involved in integrin functions in different leukocyte subtypes. Read More

    Activation of compensatory pathways via Rac2 in the absence of the Cdc42 effector Wiskott-Aldrich syndrome protein in Dendritic cells.
    Small GTPases 2017 Jan 27:1-8. Epub 2017 Jan 27.
    a Department of Microbiology Tumor and Cell Biology , Karolinska Institutet , Stockholm , Sweden.
    There is extensive crosstalk between different Rho GTPases, including Cdc42, Rac1, and Rac2, and they can activate or inhibit the activity of each other. Dendritic cells express both Rac1 and Rac2. Due to posttranslational modification of lipid anchors, Rac1 localizes mainly to the plasma membrane whereas Rac2 localizes to the phagosomal membrane where it assembles the NADPH complex. Read More

    WAVE1 in neurons expressing the D1 dopamine receptor regulates cellular and behavioral actions of cocaine.
    Proc Natl Acad Sci U S A 2017 Feb 23;114(6):1395-1400. Epub 2017 Jan 23.
    Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065;
    Wiskott-Aldrich syndrome protein (WASP) family verprolin homologous protein 1 (WAVE1) regulates actin-related protein 2/3 (Arp2/3) complex-mediated actin polymerization. Our previous studies have found WAVE1 to be inhibited by Cdk5-mediated phosphorylation in brain and to play a role in the regulation of dendritic spine morphology. Here we report that mice in which WAVE1 was knocked out (KO) in neurons expressing the D1 dopamine receptor (D1-KO), but not mice where WAVE1 was knocked out in neurons expressing the D2 dopamine receptor (D2-KO), exhibited a significant decrease in place preference associated with cocaine. Read More

    Phosphatidylinositol 3,4-bisphosphate regulates neurite initiation and dendrite morphogenesis via actin aggregation.
    Cell Res 2017 Feb 20;27(2):253-273. Epub 2017 Jan 20.
    Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China.
    Neurite initiation is critical for neuronal morphogenesis and early neural circuit development. Recent studies showed that local actin aggregation underneath the cell membrane determined the site of neurite initiation. An immediately arising question is what signaling mechanism initiated actin aggregation. Read More

    Osteomyelitis of the navicular bone: a case report.
    J Pediatr Orthop B 2017 Jan 17. Epub 2017 Jan 17.
    Department of Orthopaedics, Shimane University, Izumo, Shimane Prefecture, Japan.
    A 16-year-old boy developed left foot pain of unknown cause that was unresponsive to conservative treatment, associated with fever and difficulty walking. He was admitted to our hospital with osteomyelitis of the accessory and body of the navicular bone. Surgery could not be performed because the patient had been diagnosed with Wiskott-Aldrich syndrome. Read More

    Oncogenic KRas-induced Increase in Fluid-phase Endocytosis is Dependent on N-WASP and is Required for the Formation of Pancreatic Preneoplastic Lesions.
    EBioMedicine 2016 Dec 24. Epub 2016 Dec 24.
    Clinic and Polyclinic for Internal Medicine II, Klinikum Rechts der Isar, Technical University of Munich, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center, DKFZ, Heidelberg, Germany; Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK), Partner Site Essen, West German Cancer Center, University Hospital Essen, Germany. Electronic address:
    Fluid-phase endocytosis is a homeostatic process with an unknown role in tumor initiation. The driver mutation in pancreatic ductal adenocarcinoma (PDAC) is constitutively active KRas(G12D), which induces neoplastic transformation of acinar cells through acinar-to-ductal metaplasia (ADM). We have previously shown that KRas(G12D)-induced ADM is dependent on RAC1 and EGF receptor (EGFR) by a not fully clarified mechanism. Read More

    Gene Therapy in Fanconi anemia: a matter of time, safety and gene transfer tool efficiency.
    Curr Gene Ther 2017 01 9. Epub 2017 Jan 9.
    Division of Hematopoietic Innovative Therapies, CIEMAT/ CIBERER-ISC-III. Madrid, Spain.
    Fanconi anemia (FA) is a rare genetic syndrome characterized by progressive marrow failure. Gene therapy by infusion of FA-corrected autologous hematopoietic stem cells (HSCs) may offer a potential cure since it is a monogenetic disease with mutations in the FANC genes, coding for DNA repair enzymes (See review[1]). However, the collection of hCD34 +-cells in FA patients implies particular challenges because of the reduced numbers of progenitor cells present in their bone marrow (BM)[2] or mobilized peripheral blood[3-5]. Read More

    Oncogenic KRas-induced Increase in Fluid-phase Endocytosis is Dependent on N-WASP and is Required for the Formation of Pancreatic Preneoplastic Lesions.
    EBioMedicine 2017 Feb 24;15:90-99. Epub 2016 Dec 24.
    Clinic and Polyclinic for Internal Medicine II, Klinikum Rechts der Isar, Technical University of Munich, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center, DKFZ, Heidelberg, Germany; Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK), Partner Site Essen, West German Cancer Center, University Hospital Essen, Germany. Electronic address:
    Fluid-phase endocytosis is a homeostatic process with an unknown role in tumor initiation. The driver mutation in pancreatic ductal adenocarcinoma (PDAC) is constitutively active KRas(G12D), which induces neoplastic transformation of acinar cells through acinar-to-ductal metaplasia (ADM). We have previously shown that KRas(G12D)-induced ADM is dependent on RAC1 and EGF receptor (EGFR) by a not fully clarified mechanism. Read More

    The identification of hematopoietic-specific regulatory elements for WASp gene expression.
    Mol Ther Methods Clin Dev 2016 14;3:16077. Epub 2016 Dec 14.
    Department of Hematology, Division of Experimental Hematology , St. Jude Children's Research Hospital , Memphis, Tennessee, USA.
    Chromosome Conformation Capture (3C) technology was used to identify physical interactions between the proximal Wiskott-Aldrich Syndrome protein (WASp) promoter and its distant DNA segments in Jurkat-T cells. We found that two hematopoietic specific DNase I hypersensitive (DHS) sites (proximal DHS-A, and distal DHS-B) which had high interaction frequencies with the proximal WASp promoter indicating potential regulatory activity for these DHS sites. Subsequently, we cloned several DNA fragments around the proximal DHS-A site into a luciferase reporter vector. Read More

    A novel mutation of WAS gene in a boy with Mycobacterium bovis infection at spleen.
    Asian Pac J Allergy Immunol 2016 Dec 12. Epub 2016 Dec 12.
    Division of Allergy and Immunology, Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
    Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency disorder caused by mutations of the gene encoding WAS protein (WASp). A scoring system has been used to grade severity of the disease. However, the phenotype of the disease may progress over time, especially in children younger than 2 years of age. Read More

    Myogenic differentiation depends on the interplay of Grb2 and N-WASP.
    Biochim Biophys Acta 2017 Mar 10;1864(3):487-497. Epub 2016 Dec 10.
    School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Republic of Singapore. Electronic address:
    Myogenesis requires a well-coordinated withdrawal from cell cycle, morphological changes and cell fusion mediated by actin cytoskeleton. Grb2 is an adaptor protein whose central SH2 domain binds to phosphorylated tyrosine residues of activated receptors and activates intracellular signaling pathway, while its N-terminal and C-terminal SH3 domains bind to proline rich proteins such as N-WASP (Neural-Wiskott Aldrich Syndrome Protein). We found that the expression of Grb2 was increased at the beginning of differentiation and remained constant during differentiation in C2C12 myoblasts. Read More

    WIP promotes in-vitro invasion ability, anchorage independent growth and EMT progression of A549 lung adenocarcinoma cells by regulating RhoA levels.
    Biochem Biophys Res Commun 2017 Jan 7;482(4):1353-1359. Epub 2016 Dec 7.
    School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore. Electronic address:
    Cancer cell migration and invasion involves actin cytoskeleton reorganization, which is regulated by the WASP (Wiskott Aldrich Syndrome Protein) family of proteins such as WASP, N-WASP (Neural-WASP) and WASP interacting protein (WIP). In this study, we found that the expression of WIP was significantly upregulated in metastatic A5-RT3 cells compared to its parental non-tumorigenic HaCaT cells. Using A549 human lung adenocarcinoma cell line as the model system, we found that WIP regulates cell invasion, proliferation and anchorage-independent growth. Read More

    WASP family proteins, more than Arp2/3 activators.
    Biochem Soc Trans 2016 Oct;44(5):1339-1345
    Department of Biomedical Science, Firth Court, University of Sheffield, Sheffield S10 2TN, U.K.
    Wiskott-Aldrich syndrome protein (WASP) family proteins have been extensively characterized as factors that promote the nucleation of actin through the activation of the protein complex Arp2/3. While yeast mostly have a single member of the family, mammalian cells have at least six different members, often with multiple isoforms. Members of the family are characterized by a common structure. Read More

    Conditional knockout of N-WASP in mouse fibroblast caused keratinocyte hyper proliferation and enhanced wound closure.
    Sci Rep 2016 Dec 2;6:38109. Epub 2016 Dec 2.
    School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Republic of Singapore.
    Neural-Wiskott Aldrich Syndrome Protein (N-WASP) is expressed ubiquitously, regulates actin polymerization and is essential during mouse development. We have previously shown that N-WASP is critical for cell-ECM adhesion in fibroblasts. To characterize the role of N-WASP in fibroblast for skin development, we generated a conditional knockout mouse model in which fibroblast N-WASP was ablated using the Cre recombinase driven by Fibroblast Specific Protein promoter (Fsp-Cre). Read More

    Role of Rac1/WAVE2 Signaling in Mediating the Inhibitory Effects of γ-Tocotrienol on Mammary Cancer Cell Migration and Invasion.
    Biol Pharm Bull 2016 ;39(12):1974-1982
    School of Pharmacy, University of Louisiana at Monroe.
    The majority of breast cancer deaths result from the progression of this disease to a metastatic phenotype. Rac1 and Cdc42 are Rho family members that together with their downstream effectors, Wiskott-Aldrich Syndrome protein-family verprolin-homologous protein 2 (WAVE2) and Arp2/3, play an important role in cytoskeletal reorganization and the formation of membrane protrusions that promote cancer cell migration and invasion. γ-Tocotrienol, is a natural isoform within the vitamin E family of compounds that inhibits breast cancer cell growth and progression by suppressing various signaling pathways involved in mitogenic signaling and metastatic progression. Read More

    Low T Cell Numbers Resembling T-B+ SCID in a Patient with Wiskott-Aldrich Syndrome and the Outcome of Two Hematopoietic Stem Cell Transplantations.
    J Clin Immunol 2017 Jan 30;37(1):18-21. Epub 2016 Nov 30.
    Department of Pediatric Immunology, Hacettepe University of Medicine, İhsan Doğramacı Children's Hospital, Ankara, Turkey.

    Wiskott-Aldrich syndrome in a child presenting with macrothrombocytopenia.
    Platelets 2016 Nov 25:1-4. Epub 2016 Nov 25.
    c Centro Regional de Hemodonación , H. Universitario Morales Meseguer, IMIB-Arrixaca , Murcia, Spain.
    Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive disease resulting from variants in the WAS gene, characterized by a triad of immunodeficiency, eczema, and thrombocytopenia. Despite the fact that WAS is traditionally differentiated from immune thrombocytopenia (ITP) by small size of WAS platelets, in practice, microthrombocytopenia may occasionally not be present, and in certain cases, WAS patients exhibit some parallelism to ITP patients. We characterized one patient presenting with the classic form of the disease but increased mean platelet volume. Read More

    Drosophila WASH is required for integrin-mediated cell adhesion, cell motility and lysosomal neutralization.
    J Cell Sci 2017 Jan 24;130(2):344-359. Epub 2016 Nov 24.
    Institut für Neurobiologie, Universität Münster, Badestr. 9, 48149 Münster, Germany
    The Wiskott-Aldrich syndrome protein and SCAR homolog (WASH; also known as Washout in flies) is a conserved actin-nucleation-promoting factor controlling Arp2/3 complex activity in endosomal sorting and recycling. Previous studies have identified WASH as an essential regulator in Drosophila development. Here, we show that homozygous wash mutant flies are viable and fertile. Read More

    Successful engraftment after hematopoietic stem cell transplantation with infusion of donor stem cells through the extracorporeal membrane oxygenation circuit.
    Indian J Crit Care Med 2016 Oct;20(10):617-619
    Department of Pediatrics, Division of Critical Care Medicine, University of Texas Southwestern/Children's Health Dallas, TX, USA.
    Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency due to mutations in the WAS gene expressed in hematopoietic cells. Hematopoietic stem cell transplantation (HSCT) is the treatment of choice when an appropriate human leukocyte antigen-matched donor is available. The use of the extracorporeal membrane oxygenation (ECMO) circuit to infuse donor cells for HSCT has not been previously published in the literature. Read More

    The actin binding proteins cortactin and HS1 are dispensable for platelet actin nodule and megakaryocyte podosome formation.
    Platelets 2016 Oct 25:1-8. Epub 2016 Oct 25.
    a Institute of Cardiovascular Sciences, Institute for Biomedical Research, The Medical School, University of Birmingham , Edgbaston , Birmingham , UK.
    A dynamic, properly organised actin cytoskeleton is critical for the production and haemostatic function of platelets. The Wiskott Aldrich Syndrome protein (WASp) and Actin-Related Proteins 2 & 3 Complex (Arp2/3 complex) are critical mediators of actin polymerisation and organisation in many cell types. In platelets and megakaryocytes, these proteins have been shown to be important for proper platelet production and function. Read More

    Gene Therapy with Hematopoietic Stem Cells: The Diseased Bone Marrow's Point of View.
    Stem Cells Dev 2017 Jan 16;26(2):71-76. Epub 2016 Oct 16.
    2 Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, Assistance Publique-Hôpitaux de Paris, INSERM , Paris, France .
    When considering inherited diseases that can be treated by gene transfer into hematopoietic stem cells (HSCs), there are only two in which the HSC and progenitor cell distribution inside the bone marrow and its microenvironment are exactly the same as in a healthy subject: metachromatic leukodystrophy (MLD) and adrenoleukodystrophy (ALD). In all other settings [X-linked severe combined immunodeficiency (X-SCID), adenosine deaminase deficiency, Wiskott-Aldrich syndrome, and β-hemoglobinopathies], the bone marrow content of the different stem and precursor cells and the cells' relationship with the stroma have very specific characteristics. These peculiarities can influence the cells' harvesting and behavior in culture, and the postgraft uptake and further behavior of the gene-modified hematopoietic/precursor cells. Read More

    The C-terminal dimerization motif of cyclase-associated protein is essential for actin monomer regulation.
    Biochem J 2016 Dec 11;473(23):4427-4441. Epub 2016 Oct 11.
    Department of Pathology, Department of Cell Biology, and Winship Cancer Institute, Emory University, Atlanta, GA 30322, U.S.A.
    Cyclase-associated protein (CAP) is a conserved actin-regulatory protein that functions together with actin depolymerizing factor (ADF)/cofilin to enhance actin filament dynamics. CAP has multiple functional domains, and the function to regulate actin monomers is carried out by its C-terminal half containing a Wiskott-Aldrich Syndrome protein homology 2 (WH2) domain, a CAP and X-linked retinitis pigmentosa 2 (CARP) domain, and a dimerization motif. WH2 and CARP are implicated in binding to actin monomers and important for enhancing filament turnover. Read More

    Cdc42 in actin dynamics: An ordered pathway governed by complex equilibria and directional effector handover.
    Small GTPases 2016 Aug 11:1-8. Epub 2016 Aug 11.
    a Department of Biochemistry , University of Cambridge , Cambridge , UK.
    The small GTPase, Cdc42, is a key regulator of actin dynamics, functioning to connect multiple signals to actin polymerization through effector proteins of the Wiskott-Aldrich syndrome protein (WASP) and Transducer of Cdc42-dependent actin assembly (TOCA) families. WASP family members serve to couple Cdc42 with the actin nucleator, the Arp2/3 complex, via direct interactions. The regulation of these proteins in the context of actin dynamics has been extensively studied. Read More

    Cancers Related to Immunodeficiencies: Update and Perspectives.
    Front Immunol 2016 20;7:365. Epub 2016 Sep 20.
    Cell and Molecular Biology Group, Airways Disease Section, Faculty of Medicine, National Heart and Lung Institute, Imperial College London , London , UK.
    The life span of patients with primary and secondary immunodeficiency is increasing due to recent improvements in therapeutic strategies. While the incidence of primary immunodeficiencies (PIDs) is 1:10,000 births, that of secondary immunodeficiencies are more common and are associated with posttransplantation immune dysfunction, with immunosuppressive medication for human immunodeficiency virus or with human T-cell lymphotropic virus infection. After infection, malignancy is the most prevalent cause of death in both children and adults with (PIDs). Read More

    NPM-ALK phosphorylates WASp Y102 and contributes to oncogenesis of anaplastic large cell lymphoma.
    Oncogene 2016 Oct 3. Epub 2016 Oct 3.
    Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
    Mechanisms by which NPM-ALK signaling regulates cell migration, invasion and contributes to the oncogenesis of anaplastic large cell lymphoma (ALCL) are not completely understood. In an attempt to identify novel actin signaling pathways regulated by NPM-ALK, a comprehensive phosphoproteome analysis of ALCL cell lines was performed in the presence or absence of NPM-ALK activity. Numerous phosphoproteins involved in actin dynamics including Wiskott-Aldrich syndrome protein (WASp) were regulated by NPM-ALK. Read More

    The cell division control protein 42-Src family kinase-neural Wiskott-Aldrich syndrome protein pathway regulates human proplatelet formation.
    J Thromb Haemost 2016 Dec 15;14(12):2524-2535. Epub 2016 Nov 15.
    Institut National de la Santé et de la Recherche Médicale, UMR 1170, Equipe labellisée Ligue Contre le Cancer, Laboratoire d'Excellence GR-Ex, Villejuif, France.
    Essentials The role of the cytoskeleton during megakaryocyte differentiation was examined. Human megakaryocytes are derived from in vitro cultured CD34(+) cells. Cell division control protein 42 (CDC42) positively regulates proplatelet formation (PPF). Read More

    Postnatal cytomegalovirus infection in an infant with congenital thrombocytopenia: how it can support or mislead the diagnosis of Wiskott-Aldrich syndrome.
    Infez Med 2016 Sep;24(3):237-40
    Department of Paediatrics, Azienda Ospedaliera di Melegnano, Milan, Italy.
    A male newborn developed a post-natal cytomegalovirus (CMV) infection, arising in the clinical setting of congenital thrombocytopenia, which was diagnosed as being alloimmune. The evidence of active CMV infection in an infant showing slow-resolution lower airways infection, persistent neonatal and low platelet volume thrombocytopenia, and diffuse eczema (associated to very high levels of serum immunoglobulin E) led to the diagnosis of Wiskott-Aldrich syndrome (WAS) before the third month of life, despite the presence of several confounding clinical factors. The correct interpretation of all clinical features supported the precocious diagnosis of WAS. Read More

    FOXP3+ Tregs require WASP to restrain Th2-mediated food allergy.
    J Clin Invest 2016 Oct 19;126(10):4030-4044. Epub 2016 Sep 19.
    In addition to the infectious consequences of immunodeficiency, patients with Wiskott-Aldrich syndrome (WAS) often suffer from poorly understood exaggerated immune responses that result in autoimmunity and elevated levels of serum IgE. Here, we have shown that WAS patients and mice deficient in WAS protein (WASP) frequently develop IgE-mediated reactions to common food allergens. WASP-deficient animals displayed an adjuvant-free IgE-sensitization to chow antigens that was most pronounced for wheat and soy and occurred under specific pathogen-free as well as germ-free housing conditions. Read More

    WASP, Tregs, and food allergies - rare disease provides insight into a common problem.
    J Clin Invest 2016 Oct 19;126(10):3728-3730. Epub 2016 Sep 19.
    Dysregulation of the type 2 immune system presents with various manifestations, including allergic inflammation, and has emerged as an alarming public health issue. The pathological mechanisms that underlie T helper type 2 cell-driven (Th2-driven) allergic diseases remain unclear. In particular, it is not completely understood how type 2 immunity is restricted in inflammatory responses. Read More

    Coordinated autoinhibition of F-BAR domain membrane binding and WASp activation by Nervous Wreck.
    Proc Natl Acad Sci U S A 2016 Sep 6;113(38):E5552-61. Epub 2016 Sep 6.
    Rosenstiel Basic Medical Sciences Research Center, Department of Biology, Brandeis University, Waltham, MA 02453
    Membrane remodeling by Fes/Cip4 homology-Bin/Amphiphysin/Rvs167 (F-BAR) proteins is regulated by autoinhibitory interactions between their SRC homology 3 (SH3) and F-BAR domains. The structural basis of autoregulation, and whether it affects interactions of SH3 domains with other cellular ligands, remain unclear. Here we used single-particle electron microscopy to determine the structure of the F-BAR protein Nervous Wreck (Nwk) in both soluble and membrane-bound states. Read More

    A DOCK8-WIP-WASp complex links T cell receptors to the actin cytoskeleton.
    J Clin Invest 2016 Oct 6;126(10):3837-3851. Epub 2016 Sep 6.
    Wiskott-Aldrich syndrome (WAS) is associated with mutations in the WAS protein (WASp), which plays a critical role in the initiation of T cell receptor-driven (TCR-driven) actin polymerization. The clinical phenotype of WAS includes susceptibility to infection, allergy, autoimmunity, and malignancy and overlaps with the symptoms of dedicator of cytokinesis 8 (DOCK8) deficiency, suggesting that the 2 syndromes share common pathogenic mechanisms. Here, we demonstrated that the WASp-interacting protein (WIP) bridges DOCK8 to WASp and actin in T cells. Read More

    Association between Breast Cancer Recurrence and Cellular Dissociation Assessed Using Fine-Needle Aspiration.
    Acta Cytol 2016 1;60(5):413-420. Epub 2016 Sep 1.
    Department of Pathology, SASAKI Institute, Kyoundo Hospital, Tokyo, Japan.
    Objective: To determine the associations between breast cancer recurrence and cytological findings of fine-needle aspiration cytology (FNAC).

    Study Design: The study included 117 women who had undergone a modified radical mastectomy for invasive ductal carcinoma of the breast. FNAC samples of these patients were reexamined, and cytological findings, such as cellular dissociation, nuclear pleomorphism, nuclear atypia, chromatin pattern, and nuclear size, were scored. Read More

    Sclerosing cholangitis and intracranial lymphoma in a child with classical Wiskott-Aldrich syndrome.
    Pediatr Blood Cancer 2017 Jan 27;64(1):106-109. Epub 2016 Aug 27.
    Department of Neurosurgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
    Patients with Wiskott-Aldrich syndrome (WAS) are predisposed to malignancy and autoimmunity in addition to infections. We report a male child with WAS, who had presented with recurrent pneumonia, eczema, thrombocytopenia, autoimmune hemolytic anemia, and vasculitic skin lesions. Genetic analysis revealed a classical genotype WAS 155C>T; R41X. Read More

    LysoPCs induce Hck- and PKCδ-mediated activation of PKCγ causing p47phox phosphorylation and membrane translocation in neutrophils.
    J Leukoc Biol 2017 Jan 16;101(1):261-273. Epub 2016 Aug 16.
    Research Laboratory, Bonfils Blood Center, Denver, Colorado, USA;
    Lysophosphatidylcholines (lysoPCs) are effective polymorphonuclear neutrophil (PMN) priming agents implicated in transfusion-related acute lung injury (TRALI). LysoPCs cause ligation of the G2A receptor, cytosolic Ca(2+) flux, and activation of Hck. We hypothesize that lysoPCs induce Hck-dependent activation of protein kinase C (PKC), resulting in phosphorylation and membrane translocation of 47 kDa phagocyte oxidase protein (p47(phox)). Read More

    Polarized Exocytosis Induces Compensatory Endocytosis by Sec4p-Regulated Cortical Actin Polymerization.
    PLoS Biol 2016 Aug 15;14(8):e1002534. Epub 2016 Aug 15.
    Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
    Polarized growth is maintained by both polarized exocytosis, which transports membrane components to specific locations on the cell cortex, and endocytosis, which retrieves these components before they can diffuse away. Despite functional links between these two transport pathways, they are generally considered to be separate events. Using live cell imaging, in vivo and in vitro protein binding assays, and in vitro pyrene-actin polymerization assays, we show that the yeast Rab GTPase Sec4p couples polarized exocytosis with cortical actin polymerization, which induces endocytosis. Read More

    Alzheimer-related decrease in CYFIP2 links amyloid production to tau hyperphosphorylation and memory loss.
    Brain 2016 Oct 14;139(Pt 10):2751-2765. Epub 2016 Aug 14.
    1 Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 125 Coldharbour Lane, London, SE5 9NU, UK
    Characteristic features of Alzheimer's disease are memory loss, plaques resulting from abnormal processing of amyloid precursor protein (APP), and presence of neurofibrillary tangles and dystrophic neurites containing hyperphosphorylated tau. Currently, it is not known what links these abnormalities together. Cytoplasmic FMR1 interacting protein 2 (CYFIP2) has been suggested to regulate mRNA translation at synapses and this may include local synthesis of APP and alpha-calcium/calmodulin-dependent kinase II, a kinase that can phosphorylate tau. Read More

    Advances of gene therapy for primary immunodeficiencies.
    F1000Res 2016 9;5. Epub 2016 Mar 9.
    Division of Immunology and Allergy, University Hospital of Lausanne, Lausanne, Switzerland.
    In the recent past, the gene therapy field has witnessed a remarkable series of successes, many of which have involved primary immunodeficiency diseases, such as X-linked severe combined immunodeficiency, adenosine deaminase deficiency, chronic granulomatous disease, and Wiskott-Aldrich syndrome. While such progress has widened the choice of therapeutic options in some specific cases of primary immunodeficiency, much remains to be done to extend the geographical availability of such an advanced approach and to increase the number of diseases that can be targeted. At the same time, emerging technologies are stimulating intensive investigations that may lead to the application of precise genetic editing as the next form of gene therapy for these and other human genetic diseases. Read More

    Lymphoma Secondary to Congenital and Acquired Immunodeficiency Syndromes at a Turkish Pediatric Oncology Center.
    J Clin Immunol 2016 Oct 4;36(7):667-76. Epub 2016 Aug 4.
    Department of Pediatric Oncology, Ankara University Faculty of Medicine, Ankara, Turkey.
    The prevalence of lymphoma in primary immunodeficiency cases and autoimmune diseases, as well as on a background of immunodeficiency following organ transplants, is increasing. The lymphoma treatment success rate is known to be a low prognosis. Our study aimed to emphasize the low survival rates in immunodeficient vs. Read More

    IL-2 in the tumor microenvironment is necessary for Wiskott-Aldrich syndrome protein deficient NK cells to respond to tumors in vivo.
    Sci Rep 2016 Aug 1;6:30636. Epub 2016 Aug 1.
    Department of Microbiology Tumor and Cell biology, Karolinska Institutet, Stockholm 171 77, Sweden.
    To kill target cells, natural killer (NK) cells organize signaling from activating and inhibitory receptors to form a lytic synapse. Wiskott-Aldrich syndrome (WAS) patients have loss-of-function mutations in the actin regulator WASp and suffer from immunodeficiency with increased risk to develop lymphoreticular malignancies. NK cells from WAS patients fail to form lytic synapses, however, the functional outcome in vivo remains unknown. Read More

    Pneumocystis jirovecii pneumonia in pediatric patients: an analysis of 15 confirmed consecutive cases during 14 years.
    Korean J Pediatr 2016 Jun 30;59(6):252-5. Epub 2016 Jun 30.
    Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
    Purpose: Pneumocystis jirovecii pneumonia occurs in various immunocompromised patients. Despite the prophylaxis strategies in clinical practice, certain patients develop P. jirovecii pneumonia. Read More

    WASH has a critical role in NK cell cytotoxicity through Lck-mediated phosphorylation.
    Cell Death Dis 2016 Jul 21;7:e2301. Epub 2016 Jul 21.
    Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
    Natural killer (NK) cells are important effector cells of the innate immune system to kill certain virus-infected and transformed cells. Wiskott-Aldrich Syndrome protein (WASP) and SCAR homolog (WASH) has been identified as a member of WASP family proteins implicated in regulating the cytoskeletal reorganization, yet little is known about its function in lymphocytes. Here we demonstrate that WASH is crucial for NK cell cytotoxicity. Read More

    Deletion of Wiskott-Aldrich syndrome protein triggers Rac2 activity and increased cross-presentation by dendritic cells.
    Nat Commun 2016 Jul 18;7:12175. Epub 2016 Jul 18.
    Department of Microbiology Tumor and Cell biology, Karolinska Institutet, Stockholm 171 77, Sweden.
    Wiskott-Aldrich syndrome (WAS) is caused by loss-of-function mutations in the WASp gene. Decreased cellular responses in WASp-deficient cells have been interpreted to mean that WASp directly regulates these responses in WASp-sufficient cells. Here, we identify an exception to this concept and show that WASp-deficient dendritic cells have increased activation of Rac2 that support cross-presentation to CD8(+) T cells. Read More

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