Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2018 Apr;35(2):207-209

Medical Genetics Institute of Henan Province, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.

Objective: To detect potential mutation of the WAS gene in a Chinese family affected with Wiskott-Aldrich syndrome.

Methods: Peripheral blood samples were collected from the proband and his family members. All exons and flanking regions of the WAS gene were subjected to PCR amplification - Sanger sequencing as well as restriction endonuclease analysis. Read More

Cell Physiol Biochem 2018 Mar 29;46(2):757-764. Epub 2018 Mar 29.

Background/aims: This study aims to explore the effects of microRNA-214-5p (miR-214-5p) on the invasion and migration of Hepatocellular Carcinoma cells (HCC).

Methods: Hepatocellular Carcinoma tissues and adjacent normal tissues from 44 hepatocellular carcinoma patients were prepared for this study. The HepG2 and BEL-7402 cells were transfected with miR-214-5p mimic and inhibitor. Read More

Appl Environ Microbiol 2018 Mar 30. Epub 2018 Mar 30.

Institute of Medical Microbiology, University of Zürich, Gloriastrasse 30, 8006 Zürich, Switzerland.

The ubiquitous environmental bacterium survives and replicates within amoebae and human macrophages by forming a -containing vacuole (LCV). In an intricate process governed by the bacterial Icm/Dot type IV secretion system and a plethora of "effector proteins" the nascent LCV interferes with a number of intracellular trafficking pathways, including retrograde transport from endosomes to the Golgi apparatus. Conserved retrograde trafficking components such as the retromer coat complex or the phosphoinositide (PI) 5-phosphatase Dd5P4/OCRL restrict intracellular replication of by an unknown mechanism. Read More

Cogn Behav Neurol 2018 Mar;31(1):13-17

Department of Psychology, The Hospital for Sick Children, Toronto, Ontario, Canada.

We report the neuropsychological profile of a 6-year-old girl with Wiskott-Aldrich syndrome, a rare X-linked immunodeficiency disorder associated with thrombocytopenia, eczema, recurrent infections, and malignancy. Wiskott-Aldrich syndrome occurs almost exclusively in males and is extremely rare in females, with no known research focused on cognitive and academic functioning in this population. Our patient was referred due to concerns about her memory and academic functioning. Read More

Biol Blood Marrow Transplant 2018 Mar 14. Epub 2018 Mar 14.

Department of Hematopoietic Stem Cell Transplantation, Dmitriy Rogachev National Center for Pediatric Hematology, Oncology, and Immunology, Moscow, Russia.

Our initial experience with hematopoietic stem cell transplantation (HSCT) from a matched unrelated donor (MUD; n = 12) or a haploidentical related donor (n = 6) with T cell receptor (TCR)αβ/CD19 graft depletion in patients with Wiskott-Aldrich syndrome (WAS) (n = 18) showed a dramatic decrease in the incidence of graft-versus-host disease (GVHD) and transplantation-related mortality, with an increased overall survival (OS) of 88.9%. Unfortunately, the treatment was associated with mixed myeloid donor chimerism and secondary graft dysfunction (severe thrombocytopenia, n = 2; graft rejection, n = 5). Read More

J Cell Sci 2018 Apr 13;131(8). Epub 2018 Apr 13.

Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA 98109

WASH, a Wiskott-Aldrich syndrome (WAS) family protein, has many cell and developmental roles related to its function as a branched actin nucleation factor. Similar to mammalian WASHC1, which is embryonic lethal, Wash was found to be essential for oogenesis and larval development. Recently, however, was reported to be homozygous viable. Read More

Blood Adv 2018 Feb;2(4):401-413

Chongqing Key Laboratory of Child Infection and Immunity.

Dock8 deficiency leads to immunodeficiency, and the role of Dock8 in B-cell development and function has been revealed; however, the role of DocK8 on B-cell receptor (BCR) signaling and function of memory B cells remains elusive. In this study, we generated a Dock8 knockout mouse model and collected peripheral blood mononuclear cells from Dock8 patients to study the effect of Dock8 deficiency on the BCR signaling and activation of memory B cells with confocal microscopy and total internal reflection fluorescence microscopy. The activation of key, positive upstream BCR signaling molecules, pCD19 and phosphorylated Brutons tyrosine kinase (pBtk), is reduced. Read More

J Allergy Clin Immunol 2018 Feb 20. Epub 2018 Feb 20.

Division of Transplant Surgery and Transplantation Surgery Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass. Electronic address:

Background: Given their unique capacity for antigen uptake, processing, and presentation, antigen-presenting cells (APCs) are critical for initiating and regulating innate and adaptive immune responses. We have previously shown the role of nicotinamide adenine dinucleotide (NAD) in T-cell differentiation independently of the cytokine milieu, whereas the precise mechanisms remained unknown.

Objective: The objective of this study is to further dissect the mechanism of actions of NAD and determine the effect of APCs on NAD-mediated T-cell activation. Read More

Cytotechnology 2018 Apr 17;70(2):593-601. Epub 2018 Feb 17.

Department of Emergency Medicine, San Er Ling Yi Hospital, 783, Tian Han Road, Hanzhong City, 72300, Shanxi Province, China.

Breast tumour progression results from the advancement of the disease to a metastatic phenotype. Rac1 and Cdc42 belong to the Rho family of genes that, together with their downstream effectors, Wiskott-Aldrich Syndrome protein-family verprolin-homologous protein 2 (WAVE2) and Arp2/3, assume a vital part in cytoskeletal rearrangement and the arrangement of film projections that advance malignant cell relocation and invasion. Mangiferin is a characteristic polyphenolic compound from Mangifera indica L. Read More

J Allergy Clin Immunol 2018 Feb 13. Epub 2018 Feb 13.

International Centre for Genetic Engineering and Biotechnology, Trieste, Italy. Electronic address:

Background: Wiskott-Aldrich syndrome (WAS) is a rare primary immunodeficiency caused by mutations in Wiskott-Aldrich syndrome protein (WASp), a key regulator of cytoskeletal dynamics in hematopoietic cells. A high proportion of patients experience autoimmunity caused by a breakdown in T- and B-cell tolerance. Moreover, excessive production of type I interferon (IFN-I) by plasmacytoid dendritic cells (pDCs) contributes to autoimmune signs; however, the factors that trigger excessive innate activation have not been defined. Read More

J Allergy Clin Immunol 2018 Feb 6. Epub 2018 Feb 6.

San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy; Milan Unit, Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Milan, Italy. Electronic address:

Background: Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency characterized by eczema, infections, and susceptibility to autoimmunity and malignancies. Thrombocytopenia is a constant finding, but its pathogenesis remains elusive.

Objective: To dissect the basis of the WAS platelet defect, we used a novel conditional mouse model (CoWas) lacking Wiskott-Aldrich syndrome protein (WASp) only in the megakaryocytic lineage in the presence of a normal immunologic environment, and in parallel we analyzed samples obtained from patients with WAS. Read More

Kaohsiung J Med Sci 2018 Feb 3;34(2):122-123. Epub 2017 Oct 3.

Department of Pediatrics, Kaohsiung Veterans General Hospital, Division of Pediatric Hematology, Taiwan.

PLoS Comput Biol 2018 Feb 5;14(2):e1005972. Epub 2018 Feb 5.

Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, New Mexico, United States of America.

Mycolactone is the exotoxin produced by Mycobacterium ulcerans and is the virulence factor behind the neglected tropical disease Buruli ulcer. The toxin has a broad spectrum of biological effects within the host organism, stemming from its interaction with at least two molecular targets and the inhibition of protein uptake into the endoplasmic reticulum. Although it has been shown that the toxin can passively permeate into host cells, it is clearly lipophilic. Read More

Proc Natl Acad Sci U S A 2018 Feb 31;115(7):E1409-E1418. Epub 2018 Jan 31.

Institute of Molecular Biology, University of Oregon, Eugene, OR 97403;

Arp2/3 complex nucleates branched actin filaments important for cellular motility and endocytosis. WASP family proteins are Arp2/3 complex activators that play multiple roles in branching nucleation, but little is known about the structural bases of these WASP functions, owing to an incomplete understanding of how WASP binds Arp2/3 complex. Recent data show WASP binds two sites, and biochemical and structural studies led to models in which the WASP C segment engages the barbed ends of the Arp3 and Arp2 subunits while the WASP A segment binds the back side of the complex on Arp3. Read More

Cell Rep 2018 Jan 28;22(4):979-991. Epub 2018 Jan 28.

INSERM, UMR 1043, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France; Université Toulouse III Paul Sabatier, Toulouse, France; CNRS, UMR 5282, Toulouse, France. Electronic address:

T lymphocyte cytotoxicity relies on a synaptic ring of lymphocyte function-associated antigen 1 (LFA-1), which permits polarized delivery of lytic granules. How LFA-1 organization is controlled by underlying actin cytoskeleton dynamics is poorly understood. Here, we explored the contribution of the actin cytoskeleton regulator WASP to the topography of LFA-1 using a combination of microscopy modalities. Read More

Palliat Support Care 2018 Jan 30:1-4. Epub 2018 Jan 30.

Memorial Sloan Kettering Cancer Center,New York,New York.

Objective: Pediatric bone marrow transplants represent a medically stressful, potentially traumatic experience for children and caregivers, and psychological support for parental caregivers is paramount to their long-term well-being. However, many medical centers do not have protocols in place to sustain caregiver well-being during these distressing experiences.

Method: We report on a case of a 10-month-old infant with Wiskott Aldrich Syndrome who was hospitalized for bone marrow transplantation. Read More

World J Gastroenterol 2017 Dec;23(48):8544-8552

Department of Pediatrics, Yokohama City University, Yokohama, Kanagawa 236-004, Japan.

Aim: To screen primary immunodeficiency, Wiskott-Aldrich syndrome (WAS), and chronic granulomatous disease (CGD) among children with inflammatory bowel disease (IBD).

Methods: This was a single-center retrospective study. Eighteen children with IBD were investigated. Read More

SAGE Open Med Case Rep 2018 9;6:2050313X17753788. Epub 2018 Jan 9.

Department of Pediatrics, Showa University Fujigaoka Hospital, Yokohama, Japan.

Wiskott-Aldrich syndrome is a rare X-linked recessive disease resulting from variations in the WAS gene. Wiskott-Aldrich syndrome is sometimes difficult to differentiate from immune thrombocytopenic purpura. A 2-month-old boy was admitted to our hospital for purpura and thrombocytopenia. Read More

Elife 2018 01 16;7. Epub 2018 Jan 16.

Lymphocyte Biology Laboratory, The Francis Crick Institute, London, United Kingdom.

Wiskott-Aldrich syndrome (WAS) is an immune pathology associated with mutations in WAS protein (WASp) or in WASp interacting protein (WIP). Together with the small GTPase Cdc42 and other effectors, these proteins participate in the remodelling of the actin network downstream of BCR engagement. Here we show that mice lacking the adaptor protein ITSN2, a G-nucleotide exchange factor (GEF) for Cdc42 that also interacts with WASp and WIP, exhibited increased mortality during primary infection, incomplete protection after Flu vaccination, reduced germinal centre formation and impaired antibody responses to vaccination. Read More

Hum Mutat 2018 Apr 19;39(4):579-587. Epub 2018 Jan 19.

Laboratory of Onco-Hematology, Department of Women's and Children's Health, University of Padova, Padova, Italy.

The WAS gene product is expressed exclusively in the cytoplasm of hematopoietic cells and constitutional genetic abrogation of WASP leads to Wiskott-Aldrich syndrome (WAS). Moreover, mutational activation of WASP has been associated with X-linked neutropenia. Although studies reported that patients with constitutional WAS mutations affecting functional WASP expression may present juvenile myelomonocytic leukemia (JMML)-like features, confounding differential diagnosis above all in the copresence of mutated RAS, an activating somatic mutation of WASP has not been previously described in JMML patients. Read More

Eur J Cardiothorac Surg 2017 Dec 21. Epub 2017 Dec 21.

Department of Thoracic Surgery, Kyoto University, Sakyo-ku, Kyoto, Japan.

The authors report the first case involving a patient with Wiskott-Aldrich syndrome who underwent single living-donor lobar lung transplantation after haematopoietic stem cell transplantation. Haematopoietic stem cell transplantation was performed at 1 year of age; however, he developed severe pulmonary complications. Although lung transplantation is generally contraindicated in patients with immunodeficiency disease, the patient was able to undergo living-donor lobar lung transplantation because his immunodeficiency and thrombocytopenia were well controlled as a result of haematopoietic stem cell transplantation. Read More

Expert Rev Clin Immunol 2018 Feb 16;14(2):103-114. Epub 2018 Jan 16.

a Institute of Cellular Medicine , Newcastle University , Newcastle Upon Tyne , UK.

Introduction: Hematopoietic stem cell transplantation (HSCT) is an established curative treatment for many primary immunodeficiencies. Advances in donor selection, graft manipulation, conditioning and treatment of complications, mean that survival for many conditions is now around 90%. Next generation sequencing is identifying new immunodeficiencies, many of which are treatable with HSCT. Read More

J Allergy Clin Immunol 2017 Dec 15. Epub 2017 Dec 15.

Division of Pediatric Hematology-Oncology, Carver College of Medicine and the University of Iowa Stead Family Children's Hospital, Iowa City, Md. Electronic address:

Background: Wiskott-Aldrich syndrome (WAS), X-linked thrombocytopenia (XLT), and X-linked neutropenia, which are caused by WAS mutations affecting Wiskott-Aldrich syndrome protein (WASp) expression or activity, manifest in immunodeficiency, autoimmunity, genomic instability, and lymphoid and other cancers. WASp supports filamentous actin formation in the cytoplasm and gene transcription in the nucleus. Although the genetic basis for XLT/WAS has been clarified, the relationships between mutant forms of WASp and the diverse features of these disorders remain ill-defined. Read More

J Cell Biol 2018 Jan 12;217(1):211-230. Epub 2017 Dec 12.

Institute of Biochemistry I, Jena University Hospital/Friedrich-Schiller-University Jena, Jena, Germany

Local actin filament formation powers the development of the signal-receiving arbor of neurons that underlies neuronal network formation. Yet, little is known about the molecules that drive these processes and may functionally connect them to the transient calcium pulses observed in restricted areas in the forming dendritic arbor. Here we demonstrate that Cordon-Bleu (Cobl)-like, an uncharacterized protein suggested to represent a very distantly related, evolutionary ancestor of the actin nucleator Cobl, despite having only a single G-actin-binding Wiskott-Aldrich syndrome protein Homology 2 (WH2) domain, massively promoted the formation of F-actin-rich membrane ruffles of COS-7 cells and of dendritic branches of neurons. Read More

Platelets 2017 Dec 11:1-10. Epub 2017 Dec 11.

e Institute of Experimental Biomedicine , University Hospital Würzburg , Würzburg , Germany.

A high proportion of patients with mucocutaneous bleeding diathesis and suspected inherited or acquired platelet disorder remain without diagnosis even after comprehensive laboratory testing. Since flow cytometry allows investigation of resting and activated platelets on the single cell level by requiring only minimal amounts of blood, this method has become an important assay within the diagnostic algorithm, especially in pediatrics. We therefore developed a standardized and modular flow cytometric approach that contributes to clarify impaired platelet function in a rational step-by-step manner. Read More

ACS Chem Biol 2018 01 7;13(1):100-109. Epub 2017 Dec 7.

Department of Chemistry, and ‡Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan University , Ramat Gan, 52900, Israel.

Wiskott-Aldrich syndrome protein (WASp) is exclusively expressed in hematopoietic cells and responsible for actin-dependent processes, including cellular activation, migration, and invasiveness. The C-terminal domain of WASp-Interacting Protein (WIP) binds to WASp and regulates its activity by shielding it from degradation in a phosphorylation dependent manner as we previously demonstrated. Mutations in the WAS-encoding gene lead to the primary immunodeficiencies Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT). Read More

Dermatol Ther 2018 Mar 7;31(2):e12582. Epub 2017 Dec 7.

Unit of Dermatology and Cosmetology, IRCCS University Vita-Salute San Raffaele, Milan, Italy.

Indian Dermatol Online J 2017 Nov-Dec;8(6):391-405

Allergy Immunology Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Primary immunodeficiency disorders (PIDs) are a group of disorders affecting the capability to fight against infection. These include defects in T cells and B cells affecting cell-mediated and humoral immunity, respectively, combined humoral and cell-mediated immunodeficiency, defects in phagocytosis, complement defects, and defects in cytokine or cytokine signalling pathways which are detrimental for immune function. Depending upon the type and severity, age at onset of symptoms can vary from neonatal period to late childhood. Read More

Pediatr Hematol Oncol 2017 Aug 4;34(5):286-291. Epub 2017 Dec 4.

b Yuzuncu Yıl University, School of Medicine, Van , Turkey.

Background: The Wiskott-Aldrich syndrome (WAS) is X-linked recessive disorder associated with microplatelet thrombocytopenia, eczema, infections, and an increased risk of autoimmunity and lymphoid neoplasia. The originally described features of WAS include susceptibility to infections, microthrombocytopenia, and eczema.

Aim: In this case report, we present our experience about two cases diagnosed with a new mutation. Read More

J Clin Immunol 2018 Jan 1;38(1):7-9. Epub 2017 Dec 1.

Hematology Department, Fondazione Policlinico Universitario A. Gemelli- Università Cattolica del Sacro Cuore, Rome, Italy.

Biol Blood Marrow Transplant 2018 Mar 28;24(3):537-541. Epub 2017 Nov 28.

Center for Cell and Gene Therapy, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas. Electronic address:

Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder characterized by a triad of immunodeficiency, eczema, and thrombocytopenia. Currently, hematopoietic stem cell transplantation (HSCT) is the most reliable curative treatment with excellent results for patients with HLA-matched family or unrelated donors. However, even after fully myeloablative preparative regimens, mixed donor chimerism is a potential concern. Read More

Small GTPases 2018 Jan 29:1-7. Epub 2018 Jan 29.

b Centro de Biología Molecular Severo Ochoa (CSIC-UAM) , Madrid , Spain.

Through actin-binding proteins such as the neural Wiskott-Aldrich syndrome protein (N-WASP) and WASP-interacting protein (WIP), the Rho family GTPases RhoA, Rac1 and Cdc42 are major modulators of the cytoskeleton. (N-)WASP and WIP control Rho GTPase activity in various cell types, either by direct WIP/(N-)WASP/Cdc42 or potential WIP/RhoA binding, or through secondary links that regulate GTPase distribution and/or transcription levels. WIP helps to regulate filopodium generation and participates in the Rac1-mediated ruffle formation that determines cell motility. Read More

FASEB J 2018 Mar 3;32(3):1665-1676. Epub 2018 Jan 3.

Medizinische Klinik D, Universitätsklinikum Münster, Muenster, Germany.

Podocyte malfunction is central to glomerular diseases and is marked by defective podocyte intercellular junctions and actin cytoskeletal dynamics. Podocytes share many morphologic features with neurons, so that similar sets of proteins appear to regulate cell process formation. One such protein is the tropomyosin-related kinase C (TrkC). Read More

J Cell Biol 2017 12 17;216(12):4073-4090. Epub 2017 Nov 17.

Institute of Pharmacology, University of Bern, Bern, Switzerland

The antimicrobial defense activity of neutrophils partly depends on their ability to form neutrophil extracellular traps (NETs), but the underlying mechanism controlling NET formation remains unclear. We demonstrate that inhibiting cytoskeletal dynamics with pharmacological agents or by genetic manipulation prevents the degranulation of neutrophils and mitochondrial DNA release required for NET formation. Wiskott-Aldrich syndrome protein-deficient neutrophils are unable to polymerize actin and exhibit a block in both degranulation and DNA release. Read More

Nat Commun 2017 Nov 17;8(1):1576. Epub 2017 Nov 17.

Infection, Immunity and Inflammation Program, Great Ormond Street Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK.

Dysregulation of autophagy and inflammasome activity contributes to the development of auto-inflammatory diseases. Emerging evidence highlights the importance of the actin cytoskeleton in modulating inflammatory responses. Here we show that deficiency of Wiskott-Aldrich syndrome protein (WASp), which signals to the actin cytoskeleton, modulates autophagy and inflammasome function. Read More

J Immunol 2017 12 10;199(12):4036-4045. Epub 2017 Nov 10.

Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA 19111;

Regulation of the actin cytoskeleton is crucial for normal development and function of the immune system, as evidenced by the severe immune abnormalities exhibited by patients bearing inactivating mutations in the Wiskott-Aldrich syndrome protein (WASP), a key regulator of actin dynamics. WASP exerts its effects on actin dynamics through a multisubunit complex termed Arp2/3. Despite the critical role played by Arp2/3 as an effector of WASP-mediated control over actin polymerization, mutations in protein components of the Arp2/3 complex had not previously been identified as a cause of immunodeficiency. Read More

Oncotarget 2017 Sep 23;8(44):77152-77167. Epub 2017 Aug 23.

Institute of Medicine, Chung-Shan Medical University, Taichung, Taiwan.

Loss of immunosurveillance is a major cause of cancer progression. Here, we demonstrate that gelsolin, a constituent of ejaculate, induces apoptosis of activated lymphocytes in prostate cancer. Gelsolin was highly expressed in prostate cancer cells, and was associated with tumor progression, recurrence, metastasis, and poor prognosis. Read More

J Clin Immunol 2018 Jan 30;38(1):13-27. Epub 2017 Oct 30.

Division of Immunology and Allergy, University Hospital of Lausanne, Lausanne, Switzerland.

The Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder originally described by Dr. Alfred Wiskott in 1937 and Dr. Robert Aldrich in 1954 as a familial disease characterized by infections, bleeding tendency, and eczema. Read More

Genome Med 2017 Oct 27;9(1):91. Epub 2017 Oct 27.

Department of Microbiology Tumor and Cell biology, Karolinska Institutet, Stockholm, 171 77, Sweden.

Background: The Wiskott-Aldrich syndrome protein (WASp) family of actin-nucleating factors are present in the cytoplasm and in the nucleus. The role of nuclear WASp for T cell development remains incompletely defined.

Methods: We performed WASp chromatin immunoprecipitation and deep sequencing (ChIP-seq) in thymocytes and spleen CD4 T cells. Read More

PLoS One 2017 12;12(10):e0186288. Epub 2017 Oct 12.

University of Pécs, Medical School, Department of Biophysics, Pécs, Hungary.

Leiomodin proteins are vertebrate homologues of tropomodulin, having a role in the assembly and maintenance of muscle thin filaments. Leiomodin2 contains an N-terminal tropomodulin homolog fragment including tropomyosin-, and actin-binding sites, and a C-terminal Wiskott-Aldrich syndrome homology 2 actin-binding domain. The cardiac leiomodin2 isoform associates to the pointed end of actin filaments, where it supports the lengthening of thin filaments and competes with tropomodulin. Read More

Cell Death Dis 2017 Oct 12;8(10):e3114. Epub 2017 Oct 12.

Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.

Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by the BCR-ABL1 tyrosine kinase (TK). The development of TK inhibitors (TKIs) revolutionized the treatment of CML patients. However, TKIs are not effective to those at advanced phases when amplified BCR-ABL1 levels and increased genomic instability lead to secondary oncogenic modifications. Read More

Asian Cardiovasc Thorac Ann 2017 Nov 12;25(9):635-637. Epub 2017 Oct 12.

1 5994 Newcastle University , Newcastle-upon-Tyne, UK.

We report open surgical repair of a previously stented descending thoracic aneurysm in a patient with Wiskott-Aldrich syndrome and a platelet count <10 × 10·L. The same patient was described previously in a report of the first endovascular stent in this form of vasculitis. We describe the pre- and intraoperative management, and suggest a change in strategy in this setting. Read More

J Nippon Med Sch 2017 ;84(4):177-182

Department of Pediatrics, Nippon Medical School.

Bacterial infections often cause fatal systemic infections in patients with primary immunodeficiency. To prevent unfortunate results, the selection, dose, and dosage of antibiotics are extremely important. Here, we report a case of Wiskott-Aldrich syndrome in a patient undergoing peritoneal dialysis because of chronic renal failure in whom methicillin-resistant Staphylococcus aureus sepsis developed. Read More

J Biol Chem 2017 Nov 25;292(46):19034-19043. Epub 2017 Sep 25.

From the Departments of Biochemistry and Molecular Biology and

Defects in translocation of the glucose transporter GLUT4 are associated with peripheral insulin resistance, preclinical diabetes, and progression to type 2 diabetes. GLUT4 recruitment to the plasma membrane of skeletal muscle cells requires F-actin remodeling. Insulin signaling in muscle requires p21-activated kinase-1 (PAK1), whose downstream signaling triggers actin remodeling, which promotes GLUT4 vesicle translocation and glucose uptake into skeletal muscle cells. Read More

Biochem Biophys Rep 2017 Mar 9;9:13-21. Epub 2016 Nov 9.

School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Republic of Singapore.

Cancer cell migration and invasion involves temporal and spatial regulation of actin cytoskeleton reorganization, which is regulated by the WASP family of proteins such as N-WASP (Neural- Wiskott Aldrich Syndrome Protein). We have previously shown that expression of N-WASP was increased under hypoxic conditions. In order to characterize the regulation of N-WASP expression, we constructed an N-WASP promoter driven GFP reporter construct, N-WASP-GFP. Read More

PLoS One 2017 22;12(9):e0185076. Epub 2017 Sep 22.

Department of Biochemistry, Faculty of Medicine and Health Sciences, Rommelaere Campus, Ghent University, Ghent, Belgium.

Invasive cancer cells develop small actin-based protrusions called invadopodia, which perform a primordial role in metastasis and extracellular matrix remodelling. Neural Wiskott-Aldrich syndrome protein (N-WASp) is a scaffold protein which can directly bind to actin monomers and Arp2/3 and is a crucial player in the formation of an invadopodium precursor. Expression modulation has pointed to an important role for N-WASp in invadopodium formation but the role of its C-terminal VCA domain in this process remains unknown. Read More

Sci Rep 2017 Sep 20;7(1):11978. Epub 2017 Sep 20.

Chongqing Key Laboratory of Child Infection and Immunity, Department of Pediatric Research Institute, Ministry of Education Key Laboratory of Child Development and Disorder, International Science and Technology Cooperation base of Child development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.

Wiskott-Aldrich syndrome protein (WASp) is a key regulator of the actin cytoskeleton. Defective T - cell function is a major cause for immune deficiency in Wiskott-Aldrich syndrome (WAS) patients. T cells originate in the bone marrow and develop in the thymus, and then migrate to peripheral tissues. Read More

J Cell Biol 2017 11 18;216(11):3745-3765. Epub 2017 Sep 18.

Wellcome Trust/Cancer Research UK Gurdon Institute and Department of Biochemistry, University of Cambridge, Cambridge, England, UK

The conditional use of actin during clathrin-mediated endocytosis in mammalian cells suggests that the cell controls whether and how actin is used. Using a combination of biochemical reconstitution and mammalian cell culture, we elucidate a mechanism by which the coincidence of PI(4,5)P and PI(3)P in a curved vesicle triggers actin polymerization. At clathrin-coated pits, PI(3)P is produced by the INPP4A hydrolysis of PI(3,4)P, and this is necessary for actin-driven endocytosis. Read More

Hum Gene Ther 2018 Mar 25;29(3):366-380. Epub 2017 Oct 25.

1 Centre for Genomics and Oncological Research (GENYO), Pfizer/University of Granada/Andalusian Regional Government , Genomic Medicine Department, Granada, Spain.

Primary immunodeficiencies, including Wiskott-Aldrich syndrome (WAS), are a main target for genome-editing strategies using specific nucleases (SNs) because a small number of corrected hematopoietic stem cells could cure patients. In this work, we have designed various WAS gene-specific CRISPR/Cas9 systems and compared their efficiency and specificity with homodimeric and heterodimeric WAS-specific zinc finger nucleases (ZFNs), using K-562 cells as a cellular model and plasmid nucleofection or integration-deficient lentiviral vectors (IDLVs) for delivery. The various CRISPR/Cas9 and ZFN SNs showed similar efficiency when using plasmid nucleofection for delivery. Read More

Cancer Sci 2017 Dec 26;108(12):2358-2365. Epub 2017 Sep 26.

Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

There is increasing evidence that cytoskeleton remodeling is involved in cancer progression. Wiskott-Aldrich syndrome protein (WASP) family represents a key regulator of actin cytoskeleton remodeling. However, the underlying mechanism of the WASP family in cancer progression remains elusive. Read More