Pediatr Blood Cancer 2017 Jun 23. Epub 2017 Jun 23.

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

Wiskott-Aldrich syndrome (WAS) is an inherited X-linked disorder characterized by microthrombocytopenia, immunodeficiency, and eczema. Hematopoietic stem cell transplantation (HSCT) is the treatment of choice. Eltrombopag, a thrombopoietin receptor agonist, may be useful to prevent bleeding while awaiting HSCT. Read More

BMC Pediatr 2017 Jun 22;17(1):151. Epub 2017 Jun 22.

Instituto Nacional de Ciência e Tecnologia do Sangue, Hemocentro de Campinas, University of Campinas (Unicamp), Rua Carlos Chagas 480, Cidade Universitária "Zeferino Vaz", Campinas, SP, 13.083-878, Brazil.

Background: Thrombocytopenia can occur in different circumstances during childhood and although immune thrombocytopenia is its most frequent cause, it is important to consider other conditions, especially when there is a persistent or recurrent low platelet count. We report two cases of intermittent thrombocytopenia, previously misdiagnosed as immune thrombocytopenia.

Cases Presentation: Both cases described were boys who presented with an intermittent pattern of thrombocytopenia, with a persistently low mean platelet volume. Read More

Allergy 2017 Jun 10. Epub 2017 Jun 10.

Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, Massachusetts, USA.

Background: Food allergies are a growing health problem and the development of therapies that prevent disease onset is limited by the lack of adjuvant-free experimental animal models. We compared allergic sensitization in patients with food allergy or Wiskott-Aldrich syndrome (WAS) and defined whether spontaneous disease in Was(-/-) mice recapitulates the pathology of a conventional disease model and/or human food allergy.

Methods: Comparative ImmunoCAP ISAC microarray was performed in patients with food allergy or WAS. Read More

J Clin Immunol 2017 Jun 8. Epub 2017 Jun 8.

Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.

Purpose: Primary immunodeficiency diseases (PIDDs) are rare inherited diseases that impair the human immune system. We established a multicolor flow cytometric assay to comprehensively evaluate the immune status and immunological characteristics of patients with PIDDs.

Methods: Fifty-nine normal controls and 75 patients with PIDDs, including X-linked severe combined immunodeficiency (X-SCID), X-linked agammaglobulinemia (XLA), X-linked hyper IgM syndrome (X-HIGM), ataxia telangiectasia (AT), Wiskott-Aldrich syndrome (WAS), hyper IgE syndrome (HIES), and chronic mucocutaneous candidiasis disease (CMCD), were enrolled in this study. Read More

Exp Ther Med 2017 May 28;13(5):2151-2160. Epub 2017 Mar 28.

Cardiff China Medical Research Collaborative, Institute of Cancer and Genetics, Cardiff University School of Medicine, CF14 4XN Cardiff, UK.

Psoriasin, which is also known as S100A7, is a member of the S100 protein family, a group of calcium-responsive signalling proteins. Psoriasin expression remains high in patients with psoriasis, whereas it is downregulated in patients with invasive breast carcinoma. This observation suggests that this protein may be a notable marker of keratinocyte function and differentiation during wound healing. Read More

Anticancer Res 2017 06;37(6):3001-3007

Martin Luther University Halle-Wittenberg, Institute of Physiological Chemistry, Halle, Germany.

Background: The human melanoma cell line IGR-1 was used for the detection and regulation of both melanotransferrin (MTf) and transferrin receptor 1 (TFRC, CD71). While the function in iron transport of the TFRC is well documented the functional importance of MTf is not yet fully understood. Due to the up-regulation of TFRC by hyaluronan (HA) some components and aspects of CD44 signaling were investigated. Read More

Neurobiol Aging 2017 Aug 3;56:213.e1-213.e5. Epub 2017 May 3.

Center for Biochemistry, Institute of Biochemistry I, Medical Faculty, University of Cologne, Cologne, Germany; Department of Neurology, Heimer Institute for Muscle Research, University Hospital Bergmannsheil, Ruhr-University Bochum, Bochum, Germany. Electronic address:

Mutations of the human valosin-containing protein, p97 (VCP) and Wiskott-Aldrich syndrome protein and SCAR homolog (WASH) complex genes cause motor neuron and cognitive impairment disorders. Here, we analyzed a cohort of German patients with sporadic amyotrophic lateral sclerosis and frontotemporal lobar degeneration comorbidity (ALS/FTD) for VCP and WASH complex gene mutations. Next-generation panel sequencing of VCP, WASH1, FAM21C, CCDC53, SWIP, strumpellin, F-actin capping protein of muscle Z-line alfa 1 (CAPZA1), and CAPZB genes was performed in 43 sporadic ALS/FTD patients. Read More

J Biol Chem 2017 May 24. Epub 2017 May 24.

University of Cambridge, United Kingdom;

Cdc42 is a Rho-family small G protein that has been widely studied for its role in controlling the actin cytoskeleton and plays a part in several potentially oncogenic signalling networks. Similar to most other small G proteins, Cdc42 binds to many downstream effector proteins to elicit its cellular effects. These effector proteins all engage the same face of Cdc42, the conformation of which is governed by the activation state of the G protein. Read More

J Pediatr Hematol Oncol 2017 Jul;39(5):e267-e269

*Division of Hematology/Oncology/BMT †Department of Paediatric Laboratory Medicine, The Hospital of Sick Children, Toronto, ON, Canada.

Wiskott-Aldrich syndrome (WAS) is an X-linked disease characterized by microthrombocytopenia, eczema, immune deficiency, and autoimmune phenomena. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment. Myeloablative conditioning is the most common regimen used for HSCT in patients with WAS to avoid the risk of mixed donor chimerism and autoimmunity post-HSCT. Read More

Hum Immunol 2017 May 20. Epub 2017 May 20.

Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing, China; Division of Immunology, Children's Hospital of Chongqing Medical University, Chongqing, China. Electronic address:

Wiskott-Aldrich syndrome (WAS) is a severe and rare primary immunodeficiency. Several studies show that WAS protein (WASp) plays a key role in the function of certain lymphocyte subsets. So far, no study has described distinct immunophenotypic abnormalities associated with WAS; thus the prognostic significance of any such abnormalities is unclear. Read More

Front Immunol 2017 2;8:490. Epub 2017 May 2.

San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), Division of Regenerative Medicine, Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency caused by mutations in the gene encoding the hematopoietic-specific WAS protein (WASp). WAS is frequently associated with autoimmunity, indicating a critical role of WASp in maintenance of tolerance. The role of B cells in the induction of autoreactive immune responses in WAS has been investigated in several settings, but the mechanisms leading to the development of autoimmune manifestations have been difficult to evaluate in the mouse models of the disease that do not spontaneously develop autoimmunity. Read More

Oncotarget 2017 Jun;8(25):41189-41201

Department of Gynecological Oncology Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing 210036, China.

Background: Wiskott-Aldrich syndrome verprolin-homologous (WAVE) 3, a member of the WASP/WAVE family of proteins, plays a critical role in cell motility and acts as an oncogene in some human cancers, but no sufficient information available to illustrate its involvement in ovarian cancer tumorigenesis and progression.

Methods: The expression of WAVE3 in human ovarian cancer and normal tissue was analyzed by immunohistochemistry. WAVE3 gene and protein expression in different human ovarian cancer cell lines was tested by RT-PCR and western blotting. Read More

Indian Pediatr 2017 Apr;54(4):327-328

Department of Clinical Haematology, Haemato-Oncology and Bone Marrow (Stem cell) Transplantation *Dermatology; and #Haemato-Pathology; Christian Medical College, Ludhiana, Punjab, India. Correspondence to: M Joseph John, Department of Clinical Haematology, Haemato-Oncology and Bone Marrow (Stem Cell) Transplantation Christian Medical College, Ludhiana 141 008, Punjab, India.

Background: Allogeneic stem cell transplant is the only curative treatment for Wiskott-Aldrich syndrome.

Case Characteristics: 18-months-old boy with no sibling, cord blood or matched unrelated donor transplant options.

Outcome: Doing well 7 years after haplo-identical stem cell transplantation using unmanipulated bone marrow as the stem cell source. Read More

J Thromb Haemost 2017 Apr 29. Epub 2017 Apr 29.

Institut für Immunologie und Transfusionsmedizin, Universitätsmedizin Greifswald, Greifswald, Germany.

Essentials There are many hereditary platelet disorders (HPD) but diagnosing these is challenging. We provide a method to diagnose several HPDs using standard blood smears requiring < 100 µL blood. By this approach, the underlying cause of HPD was characterized in ~25-30% of referred individuals. Read More

Turk J Haematol 2017 Apr 13. Epub 2017 Apr 13.

Objective: Haematopoietic stem cell transplantation is a promising curative therapy for many combined primary immunodeficiencies and phagocytic disorders.

Materials And Methods: We retrospectively reviewed paediatric cases that were diagnosed with primary immunodeficiencies and scheduled for haematopoietic stem cell transplantation.

Results: We identified 22 patients (median age, 6 months; age range, 1 month to 10 years) with various diagnoses who received haematopoietic stem cell transplantation. Read More

J Autoimmun 2017 Jun 8;80:1-9. Epub 2017 Apr 8.

Massachusetts General Hospital Cancer Center and Department of Medicine Harvard Medical School, 13th Street, Charlestown, MA, 02129, USA. Electronic address:

Immune dysregulation is a prominent feature of primary immunodeficiency disorders, which commonly manifested as autoimmunity, cytopenias and inflammatory bowel disease. In partial T-cell immunodeficiency disorders, it has been proposed that the imbalance between effector and regulatory T-cells drives the breakdown of peripheral tolerance. While there is no robust test for immune dysregulation, the T-cell receptor repertoire is used as a surrogate marker, and has been shown to be perturbed in a number of immunodeficiency disorders featuring immune dysregulation including Omenn's Syndrome, Wiskott-Aldrich Syndrome, and common variable immunodeficiency. Read More

Dev Cell 2017 Apr;41(1):107-120.e4

Tsinghua-Peking Center for Life Sciences, School of Life Sciences and MOE Key Laboratory for Protein Science, Tsinghua University, Beijing 100084, China. Electronic address:

Cell-cell fusion generally requires cellular fusogenic proteins and actin-propelled membrane protrusions. However, the molecular connections between fusogens and the actin cytoskeleton remain unclear. Here, we show that the Caenorhabditis elegans fusogen EFF-1 and F-actin are enriched at the cortex of the post-embryonic fusing cells, and conditional mutations of WASP and Arp2/3 delay cell-cell fusion by impairing EFF-1 localization. Read More

Front Med (Lausanne) 2017 24;4:29. Epub 2017 Mar 24.

Biotherapy Department, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France; INSERM, Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, Assistance Publique-Hôpitaux de Paris, Paris, France; Imagine Institute, Paris Descartes-Sorbonne Paris Cité University, Paris, Italy; INSERM UMR 1163, Laboratory of Human Lymphohematopoiesis, Paris, France.

Int J Med Microbiol 2017 Jun 18;307(4-5):276-286. Epub 2017 Mar 18.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, China. Electronic address:

Chlamydia pneumoniae (C. pneumoniae) infection plays a potential role in angiogenesis. However, it is still an enigma how C. Read More

Nat Commun 2017 Apr 3;8:14816. Epub 2017 Apr 3.

Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.

Human actin-related protein 2/3 complex (Arp2/3), required for actin filament branching, has two ARPC1 component isoforms, with ARPC1B prominently expressed in blood cells. Here we show in a child with microthrombocytopenia, eosinophilia and inflammatory disease, a homozygous frameshift mutation in ARPC1B (p.Val91Trpfs*30). Read More

BMC Cancer 2017 Mar 28;17(1):224. Epub 2017 Mar 28.

Cardiff China Medical Research Collaborative, School of Medicine, Cardiff University, Cardiff, CF14 4XN, UK.

Lung cancer is one of the most commonly diagnosed cancers with survival much lower in patients diagnosed with distal metastases. It is therefore imperative to identify pathways involved in lung cancer invasion and metastasis and to consider the therapeutic potential of agents that can interfere with these molecular pathways. This study examines nWASP expression in human lung cancer tissues and explores the effect of nWASP inhibition and knockdown on lung cancer cell behaviour. Read More

Mol Ther Methods Clin Dev 2017 Mar 18;4:1-16. Epub 2016 Dec 18.

Center for Immunity and Immunotherapies and Program for Cell and Gene Therapy, Seattle Children's Research Institute, Seattle, WA 98101, USA; Department of Pediatrics, University of Washington, Seattle, WA 98105, USA; Department of Immunology, University of Washington, Seattle, WA 98105, USA.

Wiskott-Aldrich syndrome (WAS) is a life-threatening immunodeficiency caused by mutations within the WAS gene. Viral gene therapy to restore WAS protein (WASp) expression in hematopoietic cells of patients with WAS has the potential to improve outcomes relative to the current standard of care, allogeneic bone marrow transplantation. However, the development of viral vectors that are both safe and effective has been problematic. Read More

Am J Transl Res 2017 15;9(2):403-415. Epub 2017 Feb 15.

Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan UniversityWuhan, China; Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan UniversityWuhan, China.

Neural Wiskott-Aldrich syndrome protein (N-WASP) is an important member of the WASP family involved in the actin cytoskeleton reorganization. Recent evidence suggests that N-WASP may play important roles in tumor progression and metastasis. However, the contribution of N-WASP to cervical cancer is still unknown. Read More

Curr Opin Lipidol 2017 Jun;28(3):231-240

University of Groningen, University Medical Center Groningen, Department of Pediatrics, Section of Molecular Genetics, Groningen, The Netherlands.

Purpose Of Review: To highlight very recent studies identifying novel regulatory molecules and mechanisms in plasma lipid metabolism.

Recent Findings: Two novel regulatory mechanisms of LDL receptor (LDLR) intracellular trafficking have been described. The "COMMD/CCDC22/CCDC93" and "Wiskott-Aldrich syndrome protein and SCAR homologue" complexes were found to be involved in LDLR endosomal sorting and recycling, whereas the GRP94 was shown to protect LDLR from early degradation within the hepatocyte secretory pathway. Read More

Sci Rep 2017 Mar 23;7:44863. Epub 2017 Mar 23.

The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel.

WASp family Verprolin-homologous protein-2 (WAVE2), a member of the Wiskott-Aldrich syndrome protein (WASp) family of actin nucleation promoting factors, is a central regulator of actin cytoskeleton polymerization and dynamics. Multiple signaling pathways operate via WAVE2 to promote the actin-nucleating activity of the actin-related protein 2/3 (Arp2/3) complex. WAVE2 exists as a part of a pentameric protein complex known as the WAVE regulatory complex (WRC), which is unstable in the absence of its individual proteins. Read More

Bone Marrow Transplant 2017 Jun 13;52(6):913-914. Epub 2017 Mar 13.

Departments of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

J Allergy Clin Immunol 2017 Mar;139(3):726-732

Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Calif.

The most severe primary immune deficiency diseases (PIDs) have been successfully treated with allogeneic hematopoietic stem cell transplantation for more than 4 decades. However, such transplantations have the best outcomes when there is a well-matched donor available because immune complications, such as graft-versus-host disease, are greater without a matched sibling donor. Gene therapy has been developed as a method to perform autologous transplantations of a patient's own stem cells that are genetically corrected. Read More

Allergy Asthma Clin Immunol 2017 27;13:14. Epub 2017 Feb 27.

Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, Toronto, ON Canada.

The use of gene therapy (GT) for the treatment of primary immune deficiencies (PID) including severe combined immune deficiency (SCID) has progressed significantly in the recent years. In particular, long-term studies have shown that adenosine deaminase (ADA) gene delivery into ADA-deficient hematopoietic stem cells that are then transplanted into the patients corrects the abnormal function of the ADA enzyme, which leads to immune reconstitution. In contrast, the outcome was disappointing for patients with X-linked SCID, Wiskott-Aldrich syndrome and chronic granulomatous disease who received GT followed by autologous gene corrected transplantations, as many developed hematological malignancies. Read More

Haematologica 2017 Jun 2;102(6):1112-1119. Epub 2017 Mar 2.

Hôpital Saint Louis, Eurocord, Paris, France.

Wiskott-Aldrich syndrome is a severe X-linked recessive immune deficiency disorder. A scoring system of Wiskott-Aldrich syndrome severity (0.5-5) distinguishes two phenotypes: X-linked thrombocytopenia and classic Wiskott-Aldrich syndrome. Read More

Genes Chromosomes Cancer 2017 Jun 31;56(6):493-500. Epub 2017 Mar 31.

The Georgia Cancer Center, Augusta University, Augusta, Georgia, USA.

Metastasis represents an end stage in the evolution of cancer progression and has been related to specific genetic pathways. Overexpression of mutant RAS in particular appears to promote invasion and metastasis, although exactly how this occurs has not been well characterized. It was previously showed that activation of the WASF3 protein regulates actin cytoskeleton dynamics that promote invasion. Read More

Clin Immunol 2017 Jun 14;179:47-53. Epub 2017 Feb 14.

Division of Immunology Allergy and Rheumatology, Departments of Pediatrics, Pathology and Immunology, Baylor College of Medicine, United States; Center for Human Immunobiology, Texas Children's Hospital, United States.

Background: Low dose IL-2 can restore the function of T and NK cells from Wiskott-Aldrich (WAS) patients. However, the safety of in vivo IL-2 in WAS is unknown.

Objectives: A phase-I study to assess safety of low dose IL-2 in WAS. Read More

Oncotarget 2017 Apr;8(15):24988-25004

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

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

Zhongguo Dang Dai Er Ke Za Zhi 2017 Feb;19(2):250-253

Department of Respiratory Disease, Beijing Children's Hospital, Capital Medical University, 100045 Beijing, China.

J Exp Med 2017 Mar 9;214(3):851-874. 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

J Pediatr 2017 Feb;181:101

Department of Pediatrics Baylor College of Medicine Houston, Texas.

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

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

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

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

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

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

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

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

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

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

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

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

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

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