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Lancet Haematol 2019 Apr 10. Epub 2019 Apr 10.

San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy; Pediatric Immunohematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. Electronic address:

Background: Wiskott-Aldrich syndrome is a rare, life-threatening, X-linked primary immunodeficiency characterised by microthrombocytopenia, infections, eczema, autoimmunity, and malignant disease. Lentiviral vector-mediated haemopoietic stem/progenitor cell (HSPC) gene therapy is a potentially curative treatment that represents an alternative to allogeneic HSPC transplantation. Here, we report safety and efficacy data from an interim analysis of patients with severe Wiskott-Aldrich syndrome who received lentiviral vector-derived gene therapy. Read More

Lancet Haematol 2019 Apr 10. Epub 2019 Apr 10.

Division of Immunology and Allergy, Lausanne University Hospital and Lausanne University, Lausanne 1011, Switzerland. Electronic address:

Cell Immunol 2019 Apr 27;338:43-50. Epub 2019 Mar 27.

Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address:

Wiskott-Aldrich syndrome (WAS) patients are characterized by immunodeficiency and viral infections. T cells derived from WAS patients and WAS protein (WASP)-deficient mice have various defects. However, whether WASP plays a role in immune control of cytomegalovirus (CMV) infection remains unclear. Read More

Toxins (Basel) 2019 Mar 25;11(3). Epub 2019 Mar 25.

Department of Parasitology, Noguchi Memorial Institute for Medical Research, University of Ghana, P.O. Box LG 581, Legon, Accra, Ghana.

Ulcers due to infections with are characterized by complete lack of wound healing processes, painless, an underlying bed of host dead cells and undermined edges due to necrosis. Mycolactone, a macrolide produced by the mycobacterium, is believed to be the toxin responsible. Of interest and relevance is the knowledge that Buruli ulcer (BU) patients remember experiencing trauma previously at the site of the ulcers, suggesting an impairment of wound healing processes, the plausible effect due to the toxin. Read More

J Allergy Clin Immunol 2019 Mar 26. Epub 2019 Mar 26.

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: Thrombocytopenia is a serious issue for all classical Wiskott-Aldrich Syndrome (WAS) and X-linked thrombocytopenia (XLT) patients as it causes severe and life-threatening bleedings. Lentiviral gene therapy (GT) for WAS has shown promising results in terms of immune reconstitution. However, despite the reduced severity and frequency of bleeding events, platelet (PLT) counts remain low in GT -treated patients. Read More

Br J Haematol 2019 Mar 12. Epub 2019 Mar 12.

Department of Immunology, Royal Free London NHS Foundation Trust, London, UK.

Wiskott Aldrich syndrome (WAS) is a primary immunodeficiency disease resulting in recurrent infections, eczema and microthrombocytopaenia. In its classical form, significant combined immune deficiency, autoimmune complications and risk of haematological malignancy necessitate early correction with stem cell transplantation or gene therapy. A milder form, X-linked thrombocytopaenia (XLT), shares similar bleeding risk from thrombocytopaenia but is not associated with other significant clinical features and is generally managed conservatively. Read More

J Allergy Clin Immunol 2019 Feb 20. Epub 2019 Feb 20.

Clinical Hematology, Necker University Hospital, AP-HP, Paris, France; Paris Descartes University, Sorbonne Paris Cité University, Imagine Institute, Paris, France; INSERM UMR1163 & CNRS URL 8254, Laboratory of cellular and molecular mechanisms of hematological disorders and therapeutical implications, Paris, France; French National Reference Center for Primary Immune Deficiencies (CEREDIH), Necker University Hospital, AP-HP, Paris, France. Electronic address:

J Clin Immunol 2019 Feb 18;39(2):182-187. Epub 2019 Feb 18.

Department of Pediatric Hematology, Oncology, Blood and Marrow Transplantation, Apollo Hospitals, 320, Padma complex, Anna salai, Teynampet, Chennai, Tamil Nadu, 600035, India.

Haploidentical stem cell transplantation (haplo SCT) has emerged as an acceptable alternative to matched family donor transplantation for children diagnosed to have primary immune deficiency disorders (PIDs). We present data over 4 years on the challenges and efficacy of unmanipulated T cell replete haplo SCTs with post-transplant cyclophosphamide (PTCy) in children diagnosed to have PIDs. We performed a retrospective study in the pediatric blood and marrow transplantation unit where all children less than 18 years of age diagnosed to have PIDs and who underwent haplo SCT with PTCy from January 2014 to February 2018 were included in the study. Read More

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2019 Feb;27(1):246-252

Department of Hematology, The Affiliated Children's Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China.E-mail:

Objective: To investigate the gene mutation of patients with WAS gene defect and its correlation with clinical manifestations.

Methods: Thirty-one patients consulted in Children's Hospital of Soochow University from January 2013 to February 2018 were enrolled in this study. The hot pot mutations of WAS gene in 31 patients were detected and related clinical phenotypes were analyzed retrospectively. Read More

J Oral Pathol Med 2019 Jan 29. Epub 2019 Jan 29.

Department of Oral and Cranio-maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Yes-associated protein (YAP) is a candidate oncogene in various cancers including oral squamous cell carcinoma (OSCC). Our previous study demonstrated that TNF-alpha could inhibit cell proliferation and invasion by YAP phosphorylation in OSCC. However, the role of YAP in OSCC is not yet clear. Read More

PeerJ 2019 16;7:e6284. Epub 2019 Jan 16.

Department of Cellular and Molecular Biology, Centro de Investigaciones Biológicas, Spanish National Research Council (CSIC), Madrid, Spain.

Wiskott-Aldrich syndrome (WAS) is a recessive X-linked inmmunodeficiency caused by loss-of-function mutations in the gene encoding the WAS protein (WASp). WASp plays an important role in the polymerization of the actin cytoskeleton in hematopoietic cells through activation of the Arp2/3 complex. In a previous study, we found that actin cytoskeleton proteins, including WASp, were silenced in murine erythroleukemia cells defective in differentiation. Read More

Biophys J 2019 Feb 18;116(3):540-550. Epub 2018 Dec 18.

Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

The Rickettsia ∼1800-amino-acid autotransporter protein surface cell antigen 2 (Sca2) promotes actin polymerization on the surface of the bacterium to drive its movement using an actin comet-tail mechanism. Sca2 mimics eukaryotic formins in that it promotes both actin filament nucleation and elongation and competes with capping protein to generate filaments that are long and unbranched. However, despite these functional similarities, Sca2 is structurally unrelated to eukaryotic formins and achieves these functions through an entirely different mechanism. Read More

Front Genet 2018 19;9:668. Epub 2018 Dec 19.

Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

Hepatoblastoma (HB), a leading primary hepatic malignancy in children, originates from primitive hepatic stem cells. This study aimed to uncover the genetic variants that are responsible for HB oncogenesis. One family, which includes the healthy parents, and two brothers affected by HB, was recruited. Read More

J Clin Immunol 2019 Jan 3;39(1):7-10. Epub 2019 Jan 3.

Allergy and Immunology Unit, Department of Pediatrics, Advanced Pediatric Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.

PLoS One 2018 20;13(12):e0209359. Epub 2018 Dec 20.

Department of Physiology and Biophysics, VCU Program in Enteric Neuromuscular Sciences, Virginia Commonwealth University, Richmond, Virginia, United States of America.

In gastrointestinal smooth muscle, acetylcholine induced muscle contraction is biphasic, initial peak followed by sustained contraction. Contraction is regulated by phosphorylation of 20 kDa myosin light chain (MLC) at Ser19, interaction of actin and myosin, and actin polymerization. The present study characterized the signaling mechanisms involved in actin polymerization during initial and sustained muscle contraction in response to muscarinic M3 receptor activation in gastric smooth muscle cells by targeting the effectors of initial (phospholipase C (PLC)-β/Ca2+ pathway) and sustained (RhoA/focal adhesion kinase (FAK)/Rho kinase pathway) contraction. Read More

Front Immunol 2018 4;9:2756. Epub 2018 Dec 4.

Seattle Children's Research Institute, Seattle, WA, United States.

Primary immunodeficiency disorders (PIDD) comprise a group of life-threatening congenital diseases characterized by absent or impaired immune responses. Despite the fact that effective, curative treatments are available with optimal clinical outcomes when diagnosed early, newborn screening does not exist for the majority of these diseases due to the lack of detectable, specific biomarkers or validated methods for population-based screening. Peptide immunoaffinity enrichment coupled with selected reaction monitoring mass spectrometry (immuno-SRM) is a sensitive proteomic assay, involving antibody-mediated peptide capture, that allows for concurrent quantification of multiple analytes. Read More

PLoS Pathog 2018 12 14;14(12):e1007485. Epub 2018 Dec 14.

Department of Molecular and Cell Biology, Institute for Systems Genomics, University of Connecticut, Storrs, Connecticut, United States of America.

Enteropathogenic and enterohemorrhagic E. coli (EPEC and EHEC) are closely related extracellular pathogens that reorganize host cell actin into "pedestals" beneath the tightly adherent bacteria. This pedestal-forming activity is both a critical step in pathogenesis, and it makes EPEC and EHEC useful models for studying the actin rearrangements that underlie membrane protrusions. Read More

Clin Lab 2018 Oct;64(11)

Background: X-linked thrombocytopenia (XLT) is a milder form of Wiskott-Aldrich syndrome (WAS), characterized predominantly by thrombocytopenia with small-sized platelets. Mutations in the WAS gene are responsible for the disease. We herein detected a new mutation in the WAS gene responsible for XLT in a 3-generation Chinese pedigree. Read More

Am J Physiol Renal Physiol 2019 Jan 12;316(1):F186-F194. Epub 2018 Dec 12.

Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province , Shijiazhuang, Hebei , China.

Nudel is a newly discovered factor related to cell migration. The tubular epithelial-mesenchymal transition (EMT) includes four steps: the loss of the adhesive properties of epithelial cells, the acquisition of a mesenchymal cell phenotype, the destruction of the tubular basal membrane, and the migration into the renal interstitium. The purpose of this study was to investigate the role of Nudel in the high-glucose-induced EMT of tubular epithelial cells. Read More

Rom J Morphol Embryol 2018 ;59(3):839-849

Department of Dental Materials, Faculty of Dentistry, University of Medicine and Pharmacy of Craiova, Romania;

Lip cancers account for 10-12% of the total head and neck cancers and, although squamous cell carcinoma is by far the most common lower lip cancer, the basal cell carcinoma (BCC) seems to be more common for the upper lip. Most BCCs have a clinically indolent behavior, but there are also local aggressive and∕or metastatic cases, with the incidence of such cases being estimated at about 1-10% of all cases of BCC. Many of the molecular mechanisms underlying this aggression are still unknown, which is why our study aimed to investigate the potential prognosis of a few markers, such as C-X-C chemokine receptor type 4 (CXCR4), alpha-smooth muscle actin (α-SMA) and Wiskott-Aldrich syndrome like (WASL) in upper lip BCCs. Read More

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2018 Dec;26(6):1816-1821

Department of Hematology，Zhongda Hospital，Southeast University，Nanjing 210009，Jiangsu Province, China.

Objective: To explore the clinical efficacy and safety of unrelated umbilical cord blood transplantation (UCBT) for the treatment of Wiskott-Aldrich syndrome(WAS).

Methods: Five pediatric patients with WAS received single UCBT were retrospectively analyzed. The median age of these male patients was 268 days (range, 3 days -695 days). Read More

Nat Med 2019 Jan 3;25(1):130-140. Epub 2018 Dec 3.

Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.

In T lymphocytes, the Wiskott-Aldrich Syndrome protein (WASP) and WASP-interacting-protein (WIP) regulate T cell antigen receptor (TCR) signaling, but their role in lymphoma is largely unknown. Here we show that the expression of WASP and WIP is frequently low or absent in anaplastic large cell lymphoma (ALCL) compared to other T cell lymphomas. In anaplastic lymphoma kinase-positive (ALK+) ALCL, WASP and WIP expression is regulated by ALK oncogenic activity via its downstream mediators STAT3 and C/EBP-β. Read More

J Gen Virol 2019 Feb 29;100(2):176-186. Epub 2018 Nov 29.

1​Vaccine and Infectious Disease Research Centre, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.

Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, is one of the leading global causes of virus-induced encephalitis. The infectious life-cycle of viruses is heavily dependent on the host membrane trafficking network. Here, we have performed a RNA-interference-based screen using a siRNA panel targeting 136 membrane trafficking proteins to identify the key regulators of JEV infection in HeLa cells. Read More

Curr Biol 2018 Dec 21;28(23):3886-3891.e4. Epub 2018 Nov 21.

Institute of Molecular Biology and Department of Chemistry and Biochemistry, University of Oregon, 1229 University of Oregon, Eugene, OR 97403, USA. Electronic address:

When activated by Wiskott-Aldrich syndrome proteins (WASP), Arp2/3 complex nucleates branched actin filaments important for processes like cellular motility and endocytosis [1]. WASP-mediated activation of Arp2/3 complex requires a preformed actin filament, ensuring that activation by WASP creates branched instead of linear filaments. However, this biochemical requirement also means that assembly of branched actin networks must be primed with an initial seed filament [2-4]. Read More

J Clin Immunol 2018 Nov 24;38(8):917-926. Epub 2018 Nov 24.

Hospital de Clínicas da Universidade Federal do Paraná, Curitiba, Brazil.

The results of hematopoietic stem cell transplant (HSCT) for primary immunodeficiency diseases (PID) have been improving over time. Unfortunately, developing countries do not experience the same results. This first report of Brazilian experience of HSCT for PID describes the development and results in the field. Read More

Front Immunol 2018 2;9:2554. Epub 2018 Nov 2.

Division of Pediatric Hematology-Oncology, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria.

Early diagnosis of primary immunodeficiency disorders (PID) is vital and allows directed treatment, especially in syndromes with severe or profound combined immunodeficiency. In PID patients with perinatal CMV or other opportunistic, invasive infections (e.g. Read More

Diabetes 2019 Feb 13;68(2):377-386. Epub 2018 Nov 13.

Division of Oncology Research and Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, MN

WASH is an endosomal protein belonging to the Wiskott-Aldrich syndrome protein superfamily that participates in endosomal receptor trafficking by facilitating tubule fission via activation of the ubiquitously expressed Arp2/3 complex. While several studies have begun to elucidate an understanding of the functions of WASH in cells lines, the in vivo function of WASH has not been fully elucidated, since total body deletion in mice leads to early embryonic lethality. To circumvent this problem, we have used a WASH conditional knockout mouse model to investigate the role of WASH in the pancreas. Read More

Mediterr J Hematol Infect Dis 2018 1;10(1):e2018065. Epub 2018 Nov 1.

Pediatric Immunohematology Department, Bone Marrow Transplantation Center Tunis, Tunisia.

Skin manifestations are frequent among patients with primary immunodeficiency diseases (PIDs). Their prevalence varies according to the type of immunodeficiency. This review provides the reader with an up-to-date summary of the common dermatologic manifestations of PIDs among Tunisian children. Read More

Front Immunol 2018 25;9:2475. Epub 2018 Oct 25.

Department of Pathology, New York University School of Medicine, New York, NY, United States.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition caused by an aberrant immune response to microbial components of the gastrointestinal tract. Plasmacytoid dendritic cells (pDCs) are innate immune cells specialized in the production of type I interferons and were recently implicated in the pathogenesis of autoimmune disorders such as lupus and scleroderma. While pDCs were shown to infiltrate intestinal mucosa of IBD patients and proposed to participate in intestinal inflammation, their net contribution to the disease remains unclear. Read More

Neurogastroenterol Motil 2019 Feb 4;31(2):e13495. Epub 2018 Nov 4.

Department of Physiology and Biophysics, VCU Program in Enteric Neuromuscular Sciences, Virginia Commonwealth University, Richmond, Virginia.

Background: Actin polymerization plays an important role in smooth muscle contraction. Integrin-linked kinase (ILK) was shown to mediate actin polymerization in airway smooth muscle. The role of ILK in actin polymerization in response to m2 receptor activation was not in gastric smooth muscle. Read More

Oncoimmunology 2018 30;7(9):e1468954. Epub 2018 Jul 30.

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

The Wiskott-Aldrich syndrome protein (WASp) is a key regulator of the actin cytoskeleton in hematopoietic cells and mutated in two severe immunodeficiency diseases with high incidence of cancer. Wiskott-Aldrich syndrome (WAS) is caused by loss-of-function mutations in WASp and most frequently associated with lymphoreticular tumors of poor prognosis. X-linked neuropenia (XLN) is caused by gain-of-function mutations in WASp and associated with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Read More

JCI Insight 2018 11 2;3(21). Epub 2018 Nov 2.

King's British Heart Foundation Centre, King's College London, London, United Kingdom.

Fibrosis is a major contributor to organ disease for which no specific therapy is available. MicroRNA-21 (miR-21) has been implicated in the fibrogenetic response, and inhibitors of miR-21 are currently undergoing clinical trials. Here, we explore how miR-21 inhibition may attenuate fibrosis using a proteomics approach. Read More

PLoS One 2018 23;13(10):e0199341. Epub 2018 Oct 23.

Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.

NMDA receptors are important for cognition and are implicated in neuropsychiatric disorders. GluN1 knockdown (GluN1KD) mice have reduced NMDA receptor levels, striatal spine density deficits, and cognitive impairments. However, how NMDA depletion leads to these effects is unclear. Read More

Pediatr Hematol Oncol 2018 Oct 22:1-5. Epub 2018 Oct 22.

a Department of Pediatric Allergy and Immunology , Kanuni Sultan Suleyman Education and Research Hospital , Istanbul , Turkey.

Introduction: Severe congenital neutropenia (SCN) includes a group of genetic disorders which cause to arrest of neutrophil maturation. SCN can be associated with heterogenous group of genetic defects in ELANE, GFI1, HAX1, G6PC3, JAGN1, VPS45 or activating mutations in the Wiskott-Aldrich syndrome (WAS) gene.

Aim: Here we report a patient who has a HAX1 mutation presented with cyclic manner. Read More

Elife 2018 10 15;7. Epub 2018 Oct 15.

Institut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France.

The two Ral GTPases, RalA and RalB, have crucial roles downstream Ras oncoproteins in human cancers; in particular, RalB is involved in invasion and metastasis. However, therapies targeting Ral signalling are not available yet. By a novel optogenetic approach, we found that light-controlled activation of Ral at plasma-membrane promotes the recruitment of the Wave Regulatory Complex (WRC) via its effector exocyst, with consequent induction of protrusions and invasion. Read More

Curr Opin Allergy Clin Immunol 2018 12;18(6):453-458

Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, USA.

Purpose Of Review: Conventional gene therapy has been a successful, curative treatment modality for many primary immune deficiencies with significant improvements in the last decade. However, the risk of leukemic transformation with viral-mediated gene addition still remains, and unregulated gene addition is not an option for certain diseases in which the target gene is closely controlled. The recent bloom in genome modification platforms has created the opportunity to site-specifically correct mutated DNA base pairs or insert a corrective cDNA minigene while maintaining gene expression under control of endogenous regulatory elements. Read More

Immunol Cell Biol 2018 Sep 28. Epub 2018 Sep 28.

Seattle Children's Research Institute, Seattle, Washington, USA.

Hyper IgE syndromes comprise a group of rare primary immunodeficiency disorders characterized by a triad of atopic dermatitis, recurrent skin and lung infections along with elevated IgE levels. Job syndrome or autosomal dominant hyper IgE syndrome because of heterozygous loss-of-function mutations with dominant negative effect in signal transducer and activator of transcription-3 is the prototype of these disorders. However, several other genetically characterized immunodeficiency disorders have been identified over the past decade and joined the umbrella of hyper IgE syndromes including autosomal recessive mutations in the DOCK8, ZNF431 and PGM3 genes and heterozygous mutations with dominant negative effect in the CARD11 gene. Read More

Indian Pediatr 2018 Aug;55(8):661-664

Department of Pediatric Haematology, Oncology, Blood and Marrow Transplantation, Apollo Cancer Institutes, Chennai, India.

Objective: To share experience of over 15 years in hematopoietic stem cell transplantation in children with primary immunodeficiency disorders.

Design: Medical record review.

Setting: A referral center for pediatric hemato-oncological disorders. Read More

J Allergy Clin Immunol 2018 Nov 4;142(5):1444-1446. Epub 2018 Sep 4.

Rare Diseases Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Adult Immunodeficiency Unit, Infectious Diseases, Inflammation Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. Electronic address:

Cell Mol Gastroenterol Hepatol 2018 7;6(3):356-369.e1. Epub 2018 Jun 7.

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

Immunoglobulin E-mediated food allergy is rapidly developing into a global health problem. Publicly available therapeutic intervention strategies are currently restricted to allergen avoidance and emergency treatments. To gain a better understanding of the disease pathophysiology so that new therapies can be developed, major research efforts have been put into studying food allergy in mice. Read More

J Clin Immunol 2018 Oct 27;38(7):757-766. Epub 2018 Aug 27.

Division of Hematology and Oncology, Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

Purpose: We aimed to report our single-center experience of allogeneic hematopoietic cell transplantation (HCT), which has been the only curative option for certain patients with lethal primary immunodeficiencies (PIDs).

Methods: We summarized the results of HCT performed for patients with PIDs for 11 consecutive years from 2006 to 2016 at Samsung Medical Center, Seoul, Korea. Twenty-six patients with PIDs received HCT. Read More

Proc Natl Acad Sci U S A 2018 09 27;115(37):E8642-E8651. Epub 2018 Aug 27.

Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520;

We used fluorescence spectroscopy and EM to determine how binding of ATP, nucleation-promoting factors, actin monomers, and actin filaments changes the conformation of Arp2/3 complex during the process that nucleates an actin filament branch. We mutated subunits of Arp2/3 complex for labeling with fluorescent dyes at either the C termini of Arp2 and Arp3 or ArpC1 and ArpC3. We measured Förster resonance energy transfer (FRET) efficiency (ET) between the dyes in the presence of the various ligands. Read More

Mol Autism 2018 15;9:44. Epub 2018 Aug 15.

1Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, USA.

Background: Lowe syndrome (LS) is a rare genetic disorder caused by loss of function mutations in the X-linked gene, , which codes for inositol polyphosphate 5-phosphatase. LS is characterized by the triad of congenital cataracts, neurodevelopmental impairment (primarily intellectual and developmental disabilities [IDD]), and renal proximal tubular dysfunction. Studies carried out over the years have shown that hypomorphic mutations in adversely affect endosome recycling and actin polymerization in kidney cells and patient-derived fibroblasts. Read More

J Clin Invest 2018 Aug 20;128(9):4115-4131. Epub 2018 Aug 20.

Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.

Congenital neutropenia is characterized by low absolute neutrophil numbers in blood, leading to recurrent bacterial infections, and patients often require life-long granulocyte CSF (G-CSF) support. X-linked neutropenia (XLN) is caused by gain-of-function mutations in the actin regulator Wiskott-Aldrich syndrome protein (WASp). To understand the pathophysiology in XLN and the role of WASp in neutrophils, we here examined XLN patients and 2 XLN mouse models. Read More

J Biol Chem 2018 09 13;293(39):15136-15151. Epub 2018 Aug 13.

From the Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, United Kingdom

Wiskott-Aldrich syndrome protein (WASP) activates the actin-related protein 2/3 homolog (Arp2/3) complex and regulates actin polymerization in a physiological setting. Cell division cycle 42 (Cdc42) is a key activator of WASP, which binds Cdc42 through a Cdc42/Rac-interactive binding (CRIB)-containing region that defines a subset of Cdc42 effectors. Here, using site-directed mutagenesis and binding affinity determination and kinetic assays, we report the results of an investigation into the energetic contributions of individual WASP residues to both the Cdc42-WASP binding interface and the kinetics of complex formation. Read More

Heart Surg Forum 2018 07 2;21(4):E305-E306. Epub 2018 Jul 2.

Department of Cardiovascular Surgery, Istanbul University Istanbul Medical Faculty, Istanbul, Turkey.

Aortic aneurysms are a rare condition in children. Wiskott-Aldrich syndrome is a primary immunodeficiency characterized by infections, thrombocytopenia, and eczema. Aortitis and aneurysm formation seem to be progressive in patients with Wiskott-Aldrich syndrome. Read More

Dis Model Mech 2018 09 13;11(9). Epub 2018 Sep 13.

Center for Biochemistry, Institute of Biochemistry I, Medical Faculty, University of Cologne, 50931 Cologne, Germany

Hereditary spastic paraplegias (HSPs) are genetically diverse and clinically characterised by lower limb weakness and spasticity. The N471D and several other point mutations of human strumpellin (Str; also known as WASHC5), a member of the Wiskott-Aldrich syndrome protein and SCAR homologue (WASH) complex, have been shown to cause a form of HSP known as spastic paraplegia 8 (SPG8). To investigate the molecular functions of wild-type (WT) and N417D Str, we generated Str cells and ectopically expressed Str-GFP or Str-GFP in Str and WT cells. Read More

J Allergy Clin Immunol 2018 Nov 25;142(5):1654-1656.e7. Epub 2018 Jul 25.

Blood and Marrow Transplant Unit, Great Ormond Street Hospital NHS Trust, University College London, London, United Kingdom.