Research Topics
| ZAVERIO RUGGERISummaryAffiliation: The Scripps Research Institute Country: USA Publications
Research Grants
| Collaborators
|
Detail Information
Publications
Talin is required for integrin-mediated platelet function in hemostasis and thrombosisBrian G Petrich
Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
J Exp Med 204:3103-11. 2007..These data establish that platelet talin plays a crucial role in hemostasis and provide the first proof that talin is required for the activation and function of mammalian alpha2beta1 and alphaIIbbeta3 integrins in vivo...
Modulation of alpha-thrombin function by distinct interactions with platelet glycoprotein IbalphaReha Celikel
Roon Research Center for Arteriosclerosis and Thrombosis, Division of Experimental Thrombosis and Hemostasis, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Science 301:218-21. 2003..These interactions may modulate alpha-thrombin function by mediating GpIbalpha clustering and cleavage of protease-activated receptors, which promote platelet activation, while limiting fibrinogen clotting through blockade of exosite I...- Activation-independent platelet adhesion and aggregation under elevated shear stressZaverio M Ruggeri
The Scripps Research Institute MEM 175, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Blood 108:1903-10. 2006..Platelet and VWF modulation by hydrodynamic force is a mechanism for activation-independent aggregation that may support thrombotic arterial occlusion... - Comparison of VerifyNow-P2Y12 test and Flow Cytometry for monitoring individual platelet response to clopidogrel. What is the cut-off value for identifying patients who are low responders to clopidogrel therapy?Cosmo Godino
Department of Cardio Thoracic and Vascular Diseases, San Raffaele Scientific Institute, Milan, Italy
Thromb J 7:4. 2009..abstract:.. - Type IIB von Willebrand disease: a paradox explains how von Willebrand factor worksZ M Ruggeri
Roon Center for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
J Thromb Haemost 2:2-6. 2004..The net result is an apparent paradox, since the presence of a hyperfunctional adhesive molecule in blood causes a bleeding tendency. Here I recall how my colleagues and I managed to understand what goes on in these patients... - Platelet and von Willebrand factor interactions at the vessel wallZ M Ruggeri
Roon Center for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
Hamostaseologie 24:1-11. 2004.... 
Unravelling the mechanism and significance of thrombin binding to platelet glycoprotein IbZaverio M Ruggeri
Roon Research Center for Arteriosclerosis and Thrombosis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
Thromb Haemost 104:894-902. 2010..We review here published information on these topics and touch upon ongoing studies aimed at finding definitive answers to outstanding questions relevant for a better understanding of thrombosis and haemostasis...- Platelet interactions with vessel wall components during thrombogenesisZaverio M Ruggeri
Roon Center for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis, Department of Molecular and Experimental Medicine, The Scripps Research Institute MEM 175, La Jolla, CA 92037, USA
Blood Cells Mol Dis 36:145-7. 2006..We discuss the interrelationships of platelet glycoprotein receptors, von Willebrand factor, collagen, non-collagen matrix protein, and vascular cells in the complex events of platelet plug and subsequent thrombus formation... - The role of von Willebrand factor in thrombus formationZaverio M Ruggeri
The Scripps Research Institute, La Jolla, California, USA
Thromb Res 120:S5-9. 2007..This VWF-mediated process may be a key determinant of platelet accumulation in stenotic arteries leading to acute thrombotic occlusion... - Adhesion mechanisms in platelet functionZaverio M Ruggeri
The Roon Research Center for Arteriosclerosis and Thrombosis, Division of Blood Cell and Vascular Biology, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
Circ Res 100:1673-85. 2007.... - Von Willebrand factor: looking back and looking forwardZaverio M Ruggeri
The Scripps Research Institute, MEM 175, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
Thromb Haemost 98:55-62. 2007..Many challenges remain, along with the hope of translating the knowledge acquired into new and efficacious treatments for arterial thrombosis... - Platelet adhesion under flowZaverio M Ruggeri
Roon Research Center for Arteriosclerosis and Thrombosis, Division of Blood Cell and Vascular Biology, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
Microcirculation 16:58-83. 2009..The adaptation of platelet-adhesive functions to the effects of blood flow is the main focus of this review... - Von Willebrand factor, platelets and endothelial cell interactionsZ M Ruggeri
Roon Research Laboratory for Arteriosclerosis and Thrombosis, Division of Experimental Thrombosis and Hemostasis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA
J Thromb Haemost 1:1335-42. 2003.... - Platelets in atherothrombosisZaverio M Ruggeri
Department of Molecular and Experimental Medicine The Scripps Research Institute, La Jolla, California, USA
Nat Med 8:1227-34. 2002 - Contribution of distinct adhesive interactions to platelet aggregation in flowing bloodZ M Ruggeri
Roon Research Center for Arteriosclerosis and Thrombosis, The Division of Experimental Hemostasis and Thrombosis, The Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA
Blood 94:172-8. 1999..The specific function of distinct adhesion pathways in response to changing hemodynamic conditions helps to explain hemostatic and thrombotic processes... - Structure and function of the von Willebrand factor A1 domainKottayil I Varughese
Roon Research Center for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
Curr Protein Pept Sci 3:301-12. 2002..In this review, we present the current knowledge on the structural features of the VWF A1 domain that support its functions... - Von Willebrand factorZaverio M Ruggeri
Room Research Laboratory for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
Curr Opin Hematol 10:142-9. 2003..This progress in basic research has provided critical information to define with greater precision the role of von Willebrand factor in vascular biology and pathology... - Role of von Willebrand factor in platelet thrombus formationZ M Ruggeri
Roon Research Center for Arteriosclerosis and Thrombosis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
Ann Med 32:2-9. 2000..Advances in understanding the structure and function of von Willebrand factor indicate that this protein, for its unique biomechanical properties, may be a potentially useful target of antithrombotic drugs... - Mechanisms initiating platelet thrombus formationZ M Ruggeri
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA
Thromb Haemost 78:611-6. 1997.... - Role for ADAP in shear flow-induced platelet mechanotransductionAna Kasirer-Friede
Department of Medicine, University of California San Diego, La Jolla, CA 92093 0726, USA
Blood 115:2274-82. 2010..These results establish that ADAP is an essential component of alphaIIbbeta3-mediated platelet mechanotransduction that promotes F-actin assembly and enables platelet spreading and thrombus stabilization under fluid shear stress... - Functional self-association of von Willebrand factor during platelet adhesion under flowBrian Savage
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 99:425-30. 2002..The self-assembly of VWF multimers on an injured vascular surface may provide a relevant contribution to the arrest of flowing platelets opposing hemodynamic forces, thus facilitating subsequent thrombus growth... - New perspectives on von Willebrand factor functions in hemostasis and thrombosisGrazia Loredana Mendolicchio
Roon Research Laboratory for Arteriosclerosis and Thrombosis, Division of Experimental Thrombosis and Hemastasis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
Semin Hematol 42:5-14. 2005..Developments in these areas of research will refine our understanding of the role played by VWF in vascular biology and pathology... - Size regulation of von Willebrand factor-mediated platelet thrombi by ADAMTS13 in flowing bloodRoberta Donadelli
Department of Molecular and Experimental Medicine, Division of Experimental Hemostasis and Thrombosis, Roon Center for Arteriosclerosis and Thrombosis, The Scripps Research Institute-MEM 175, 10550 North Torrey Pines Rd, La Jolla, CA 92037, USA
Blood 107:1943-50. 2006..ADAMTS13, therefore, may regulate thrombus size preferentially when the cohesion between platelets depends on VWF binding induced by pathologically elevated shear stress... - Lateral clustering of platelet GP Ib-IX complexes leads to up-regulation of the adhesive function of integrin alpha IIbbeta 3Ana Kasirer-Friede
Departments of Cell Biology and Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
J Biol Chem 277:11949-56. 2002..By extrapolation, GP Ib-IX clustering in platelets may promote thrombus formation... - Platinum-induced space-group transformation in crystals of the platelet glycoprotein Ib alpha N-terminal domainKottayil I Varughese
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
Acta Crystallogr D Biol Crystallogr 60:405-11. 2004..The tetragonal crystal structure was subsequently solved using molecular-replacement techniques using the monoclinic structure as the search model and was refined with 1.7 A resolution data... - The Modifier of hemostasis (Mh) locus on chromosome 4 controls in vivo hemostasis of Gp6-/- miceYann Cheli
Roon Research Center for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
Blood 111:1266-73. 2008..9, P < .0001) that we designate Modifier of hemostasis (Mh). Our results indicate that one or more modifier genes in Mh control the extent to which in vivo platelet thrombus formation is disrupted by the absence of platelet GPVI... - Signaling through GP Ib-IX-V activates alpha IIb beta 3 independently of other receptorsAna Kasirer-Friede
Department of Cell Biology, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
Blood 103:3403-11. 2004..These data establish that GP Ib-IX-V itself can signal to activate alpha IIb beta 3, through sequential actions of Src kinases, Ca(2+) oscillations, and PI 3-kinase/PKC... - A single amino acid change in the binding pocket alters specificity of an anti-integrin antibody AP7.4 as revealed by its crystal structureSona Vasudevan
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
Blood Cells Mol Dis 32:176-81. 2004..Hence, the flexibility of the RGD-carrying loop observed in the crystal structure may stem from the fact that the antibody molecule mimics the function of these cell adhesion molecules... - The contribution of glycoprotein VI to stable platelet adhesion and thrombus formation illustrated by targeted gene deletionKazunobu Kato
Roon Research Center for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA
Blood 102:1701-7. 2003..These results illustrate the role of GP VI in postadhesion events leading to the development of platelet thrombi on collagen fibrils... - Platelets prevent IFN-alpha/beta-induced lethal hemorrhage promoting CTL-dependent clearance of lymphocytic choriomeningitis virusMatteo Iannacone
Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 105:629-34. 2008.... - Platelets mediate cytotoxic T lymphocyte-induced liver damageMatteo Iannacone
Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
Nat Med 11:1167-9. 2005..Thus, activated platelets contribute to CTL-mediated liver immunopathology independently of procoagulant function... - Hyperantithrombotic, noncytoprotective Glu149Ala-activated protein C mutantLaurent O Mosnier
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
Blood 113:5970-8. 2009..Protein engineering can provide APC mutants that permit definitive mechanism of action studies for APC's multiple activities, and may also provide safer and more effective second-generation APC mutants with reduced bleeding risk... - HBV pathogenesis in animal models: recent advances on the role of plateletsMatteo Iannacone
Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
J Hepatol 46:719-26. 2007.... - Antiplatelet drug therapy moderates immune-mediated liver disease and inhibits viral clearance in mice infected with a replication-deficient adenovirusMatteo Iannacone
Department of Molecular and Experimental Medicine, Scripps Research Institute, 10550 North Torrey Pines Rd, La Jolla, CA 92037, USA
Clin Vaccine Immunol 14:1532-5. 2007.... - Contribution of leptin receptor N-linked glycans to leptin bindingYuichi Kamikubo
Roon Research Center for Arteriosclerosis and Thrombosis, Division of Blood Cell and Vascular Biology, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
Biochem J 410:595-604. 2008..Our findings show that N-linked glycans within Ig and/or FNIII domains regulate Ob-R function, but are not involved in essential interactions with the ligand... - Tensile destruction test as an estimation of partial proteolysis in fibrin clotsENRIQUE SALDIVAR
Roon Research Center for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
Am J Hematol 71:119-27. 2002..Our findings suggest that when the fibers are cleaved their capacity to withstand stress is seriously challenged; thus, in principle, tensile destruction test can detect a minimal degree of proteolysis... - Altered von Willebrand factor subunit proteolysis and multimer processing associated with the Cys2362Phe mutation in the B2 domainAlessandra Casonato
Dept of Medical and Surgical Sciences, Via Ospedale Civile 105, Padova, Italy
Thromb Haemost 97:527-33. 2007..Our findings indicate that a proper conformation of the B2 domain, which depends on critical Cys residues, may be required for the normal proteolytic processing of vWF multimers... - Mechanism of platelet adhesion to von Willebrand factor and microparticle formation under high shear stressArmin J Reininger
Department of Transfusion Medicine and Hemostaseology, University Clinic Munich, Ziemssenstr 1, 80336 Munich, Germany
Blood 107:3537-45. 2006.... - Sequential cytoplasmic calcium signals in a 2-stage platelet activation process induced by the glycoprotein Ibalpha mechanoreceptorMario Mazzucato
Servizio Immunotrasfusionale e Analisi Cliniche, Centro di Riferimento Oncologico, Aviano, Italy
Blood 100:2793-800. 2002..Our conclusions modify those proposed by others regarding the mechanisms that regulate signaling between GPIbalpha and alpha(IIb)beta(3) and lead to platelet adhesion and aggregation on immobilized VWF... - The role of the porcine von Willebrand factor: baboon platelet interactions in pulmonary xenotransplantationJeffrey G Gaca
Department of Surgery, Duke University Medical Center, Durham, NC, USA
Transplantation 74:1596-603. 2002..Aberrant interactions between pvWF and GPIb play a significant role in DIC associated with pulmonary xenotransplantation... - A sensitive ristocetin co-factor activity assay with recombinant glycoprotein Ibalpha for the diagnosis of patients with low von Willebrand factor levelsAugusto B Federici
Angelo Bianchi Bonomi Hemophilia Thrombosis Center, Department of Internal Medicine and Dermatology, IRCCS Maggiore Hospital and University of Milan, Italy
Haematologica 89:77-85. 2004..A correct diagnosis of VWD relies on platelet agglutination tests that have a low accuracy within and between assays. A more accurate VWF:RCo assay would improve VWD diagnosis and classification... - Induction of platelet thrombi by bacteria and antibodiesUlf Sjöbring
Section for Microbiology, Immunology and Glycobiology, the Institute of Laboratory Medicine, University of Lund, Lund, Sweden
Blood 100:4470-7. 2002.... - Distinct roles of ADP receptors in von Willebrand factor-mediated platelet signaling and activation under high flowMario Mazzucato
Blood Bank, Centro di Riferimento Oncologico Istituto di Ricerca e Cura e Carattere Scientifico, National Cancer Institute, Aviano PN, Italy
Blood 104:3221-7. 2004.... - Factor XI interacts with the leucine-rich repeats of glycoprotein Ibalpha on the activated plateletFrank A Baglia
Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA
J Biol Chem 279:49323-9. 2004..We conclude that FXI binds to glycoprotein Ibalpha at sites comprising the leucine-rich repeat sequences within the NH2-terminal globular domain that are separate and distinct from the thrombin-binding site... - The role of platelet adhesion receptor GPIbalpha far exceeds that of its main ligand, von Willebrand factor, in arterial thrombosisWolfgang Bergmeier
CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 103:16900-5. 2006..Thus, GPIbalpha contributes to arterial thrombosis by important adhesion mechanisms independent of the binding to VWF... - Dependence of platelet thrombus stability on sustained glycoprotein IIb/IIIa activation through adenosine 5'-diphosphate receptor stimulation and cyclic calcium signalingShinya Goto
Department of Medicine, Tokai University School of Medicine, Kanagawa, Japan
J Am Coll Cardiol 47:155-62. 2006..We sought to evaluate the mechanisms that support the stability of platelet aggregates on a thrombogenic surface exposed to flowing blood... - Platelets and platelet adhesion support angiogenesis while preventing excessive hemorrhageJanka Kisucka
CBR Institute for Biomedical Research, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 103:855-60. 2006..The adhesion function of platelets, as mediated by GPIbalpha, significantly contributes to the process... - A role of the fast ATP-gated P2X1 cation channel in thrombosis of small arteries in vivoBeatrice Hechler
Institut National de la Santé et de la Recherche Médicale INSERM U 311, EFS Alsace 10, rue Spielmann, BP No 36, 67065 Strasbourg Cedex, France
J Exp Med 198:661-7. 2003..Overall, the P2X1 receptor appears to contribute to the formation of platelet thrombi, particularly in arteries in which shear forces are high... - ADAP is required for normal alphaIIbbeta3 activation by VWF/GP Ib-IX-V and other agonistsAna Kasirer-Friede
Department of Medicine, University of California San Diego, La Jolla 92093 0726, USA
Blood 109:1018-25. 2007..These studies establish ADAP as a component of inside-out signaling pathways that couple GP Ib-IX-V and other platelet agonist receptors to alphaIIbbeta3 activation... - Eph kinases and ephrins support thrombus growth and stability by regulating integrin outside-in signaling in plateletsNicolas Prevost
Department of Medicine, and Center for Experimental Therapeutics, University of Pennsylvania, 421 Curie Boulevard, Philadelphia, PA 19104, USA
Proc Natl Acad Sci U S A 102:9820-5. 2005.... - Molecular bases of defective signal transduction in the platelet P2Y12 receptor of a patient with congenital bleedingMarco Cattaneo
A Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Internal Medicine, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Maggiore, University of Milan, 20122 Milan, Italy
Proc Natl Acad Sci U S A 100:1978-83. 2003..These studies delineate a region of P2Y(12) required for normal function after ADP binding... - In-vitro and in-vivo consequences of mutations in the von Willebrand factor cleaving protease ADAMTS13 in thrombotic thrombocytopenic purpuraRoberta Donadelli
Mario Negri Institute for Pharmacological Research, Clinical Research Center for Rare Diseases, Villa Camozzi, Via Camozzi, 3, 24020 Ranica, Bergamo, Italy
Thromb Haemost 96:454-64. 2006..In conclusion, defective secretion and impaired activity of the mutants concur to determine an almost complete deficiency of ADAMTS13 activity in patients with a homozygous or two heterozygous ADAMTS13 mutations... - Laminin stimulates spreading of platelets through integrin alpha6beta1-dependent activation of GPVIOsamu Inoue
Department of Clinical and Laboratory Medicine, Yamanashi Medical University, 1110 Shimokato Tamaho Nakakoma, Yamanashi 409 3898, Japan
Blood 107:1405-12. 2006..We speculate that laminin contributes to platelet spreading in vivo through a direct interaction with GPVI...
Research Grants
- Role of von Willebrand Factor in Platelet Thrombus FormationZaverio M Ruggeri; Fiscal Year: 2010..Understanding these different functions requires addressing structural details as well as verification of concepts in intravidal models. This will lead to a better diagnosis and treatment for cardio- and cerebro-vascular diseases. ..
- Initiation and Regulation of Platelet Thrombus FormationZAVERIO RUGGERI; Fiscal Year: 2004..The results of the proposed studies will have an impact on public health by providing novel mechanistic information on processes that are central to normal hemostasis and pathological arterial thrombosis. ..
- Structure and function of platelet membrane glycoproteinsZaverio M Ruggeri; Fiscal Year: 2010..This new knowledge may translate into improved diagnosis and treatment of common and serious diseases, thus enhancing human health. ..
- Thrombus Formation and Antithrombotic InterventionZAVERIO RUGGERI; Fiscal Year: 2007..abstract_text> ..
- Structure and function of platelet membrane glycoproteinsZAVERIO RUGGERI; Fiscal Year: 2007..abstract_text> ..
- Mechanisms of Thrombus InstabilityZAVERIO RUGGERI; Fiscal Year: 2007..These studies will provide novel insights into the unexpected role of leptin in platelet function, and in the formation and stability of thrombi. ..
- Platelet interactions with vessel wall componentsZAVERIO RUGGERI; Fiscal Year: 2005..These findings will provide a better definition and characterization of several potential targets for antithrombotic intervention that may yield new treatments for patients at risk of cardiovascular and cerebrovascular events. ..
- Structure and function of platelet membrane glycoproteinsZaverio M Ruggeri; Fiscal Year: 2011..This new knowledge may translate into improved diagnosis and treatment of common and serious diseases, thus enhancing human health. ..