Research Topics
Genomes and Genes
| Mortimer PonczSummaryAffiliation: The Children's Hospital of Philadelphia Country: USA Publications
Research Grants
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Detail Information
Publications
Intracellular interaction of von Willebrand factor and factor VIII depends on cellular context: lessons from platelet-expressed factor VIIIHelen Yarovoi
Department of Pediatrics, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
Blood 105:4674-6. 2005..It appears that FVIII's interaction with VWF and its intracellular transportation, storage, and secretion differ greatly depending on the cell type. The molecular basis for these differences now needs to be elucidated...
Infusion of mature megakaryocytes into mice yields functional plateletsRudy Fuentes
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
J Clin Invest 120:3917-22. 2010..These data suggest that it may be unnecessary to generate platelets from ex vivo grown megakaryocytes to achieve clinically relevant increases in platelet numbers...- Mechanistic basis of heparin-induced thrombocytopeniaMortimer Poncz
Children s Hospital of Philadelphia, University of Pennsylvania School of Medicine, 34th Street and Civic Center Blvd, Philadelphia, PA 19104, USA
Semin Thorac Cardiovasc Surg 17:73-9. 2005..These events, in turn, further stimulate PF4 release, perpetuating repetitive cycle that results in the clinical manifestations of this disorder... - Megakaryocyte biology and related disordersLiyan Pang
Division of Hematology, Children s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Pennsylvania 19104, USA
J Clin Invest 115:3332-8. 2005..It is anticipated that the growing knowledge in these areas may be exploited for new therapeutic strategies to modulate both platelet numbers and their thrombogenicity... - Targeting recombinant thrombomodulin fusion protein to red blood cells provides multifaceted thromboprophylaxisSergei Zaitsev
Program in Targeted Therapeutics, Institute for Translational Medicine and Therapeutics, and Department of Pharmacology, University of Pennsylvania School of Medicine, 3400 Civic Center Blvd, Philadelphia, PA 19104 5158, USA
Blood 119:4779-85. 2012..Thus, scFv/TM serves as a prodrug and provides thromboprophylaxis at low doses (0.15 mg/kg) via multifaceted mechanisms inhibiting platelets and coagulation... - Monocyte-bound PF4 in the pathogenesis of heparin-induced thrombocytopeniaLubica Rauova
Department of Pediatrics, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
Blood 116:5021-31. 2010.... - Pleiotropic platelet defects in mice with disrupted FOG1-NuRD interactionYuhuan Wang
Division of Hematology, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
Blood 118:6183-91. 2011.... - NuRD mediates activating and repressive functions of GATA-1 and FOG-1 during blood developmentAnnarita Miccio
Division of Hematology, The Children s Hospital of Philadelphia, Philadelphia, PA, USA
EMBO J 29:442-56. 2010..These results show that NuRD is a critical co-factor for FOG-1 and underscore the versatile use of NuRD by lineage-specific transcription factors to activate and repress gene transcription in the appropriate cellular and genetic context... - Dynamic antibody-binding properties in the pathogenesis of HITBruce S Sachais
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Blood 120:1137-42. 2012..These differences suggest the potential importance of epitope specificity in the pathogenesis of HIT... - Sustained thromboprophylaxis mediated by an RBC-targeted pro-urokinase zymogen activated at the site of clot formationSergei Zaitsev
Program in Targeted Therapeutics, Institute for Translational Medicine and Therapeutics and Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia 19104 6068, USA
Blood 115:5241-8. 2010..Thus, prophylactic delivery of RBC-targeted PA pro-drugs activated selectively at the site of clot formation represents a new approach to prevent thrombosis in clinical settings where the risk of clotting is high... - Role of platelet surface PF4 antigenic complexes in heparin-induced thrombocytopenia pathogenesis: diagnostic and therapeutic implicationsLubica Rauova
Department of Pediatrics, The Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
Blood 107:2346-53. 2006..We believe that this focus on surface PF4 advances our understanding of the pathogenesis of HIT, suggests ways to identify patients at high risk to develop HIT upon heparin exposure, and offers new therapeutic strategies... - Antibodies associated with heparin-induced thrombocytopenia (HIT) inhibit activated protein C generation: new insights into the prothrombotic nature of HITM Anna Kowalska
Department of Pediatrics, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
Blood 118:2882-8. 2011..Recognition of these complexes by HIT antibodies reverses the PF4-dependent enhancement in aPC generation and may contribute to the prothrombotic nature of HIT... - The role of platelet factor 4 in radiation-induced thrombocytopeniaMichele P Lambert
Department of Pediatrics, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
Int J Radiat Oncol Biol Phys 80:1533-40. 2011..Factors affecting the severity of radiation-induced thrombocytopenia (RIT) are not well described. We address whether platelet factor 4 (PF4; a negative paracrine for megakaryopoiesis) affects platelet recovery postradiation... 
Role of the platelet chemokine platelet factor 4 (PF4) in hemostasis and thrombosisM Anna Kowalska
Department of Pediatrics, University of Pennsylvania School of Medicine, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
Thromb Res 125:292-6. 2010....- FOG1 requires NuRD to promote hematopoiesis and maintain lineage fidelity within the megakaryocytic-erythroid compartmentGregory D Gregory
Division of Hematology, Children s Hospital of Philadelphia, PA 19104, USA
Blood 115:2156-66. 2010..Instead, the continuous presence of GATA1, FOG1, and NuRD is required to maintain lineage fidelity throughout MK-erythroid ontogeny... - SLC35D3 delivery from megakaryocyte early endosomes is required for platelet dense granule biogenesis and is differentially defective in Hermansky-Pudlak syndrome modelsRonghua Meng
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Perelman School of Medicine, 513 Stellar Chance Laboratories, 422 Curie Blvd, Philadelphia, PA 19104 6100, USA
Blood 120:404-14. 2012.... - Species differences in small molecule binding to alpha IIb beta 3 are the result of sequence differences in 2 loops of the alpha IIb beta propellerRamesh B Basani
Division of Hematology, Children s Hospital of Philadelphia, PA19104, USA
Blood 113:902-10. 2009..Our data suggest that these species amino acids differences in the alphaIIb beta-propeller represent an evolutionary response by rodents to maintain hemostasis while concurrently protecting against RGD-containing toxins... - Platelet factor 4 is a negative autocrine in vivo regulator of megakaryopoiesis: clinical and therapeutic implicationsMichele P Lambert
Department of Pediatrics, Children s Hospital of Philadelphia, PA 19104, USA
Blood 110:1153-60. 2007..These individuals with high levels of platelet PF4 may be especially sensitive to developing thrombocytopenia after bone marrow injury and may benefit from approaches that block the effects of released PF4... - Ultralarge complexes of PF4 and heparin are central to the pathogenesis of heparin-induced thrombocytopeniaLubica Rauova
Division of Hematology, Children s Hospital of Philadelphia, PA, USA
Blood 105:131-8. 2005.... - Interactions of platelet factor 4 with the vessel wallBruce S Sachais
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Semin Thromb Hemost 30:351-8. 2004..Certainly, future studies using in vivo models to test biological relevance of each of these proposed mechanisms by which PF4 interacts with the vasculature are needed, as are studies to define the importance of PF4 binding to CXCR3B... - Factor VIII ectopically expressed in platelets: efficacy in hemophilia A treatmentHelen V Yarovoi
The Children's Hospital of Philadelphia, 1 Civic Center, ARC, Rm 317, Philadelphia, PA 19104, USA
Blood 102:4006-13. 2003..Our studies also suggest that platelet-released factor VIII is at least as potent as an equivalent plasma level and perhaps even more potent in an arterial thrombosis model... - Determinants of PF4/heparin immunogenicityShayela Suvarna
Division of Hematology, Duke University Medical Center, Durham, NC 27710, USA
Blood 110:4253-60. 2007.... - Endogenous platelet factor 4 stimulates activated protein C generation in vivo and improves survival after thrombin or lipopolysaccharide challengeM Anna Kowalska
Division of Hematology, The Children s Hospital of Philadelphia, PA 19104, USA
Blood 110:1903-5. 2007..These studies suggest that endogenous PF4 release may have biologic consequences for APC generation and survival in clinical sepsis. Infusions of PF4-rich platelets may be an effective strategy to improve outcome in this setting... - PF4/heparin complexes are T cell-dependent antigensShayela Suvarna
Division of Hematology, DUMC Box 3486, Rm 301 Alex H. Sands Bldg, Research Dr, Durham, NC 27710, USA
Blood 106:929-31. 2005..In contrast, athymic mice did not develop HIT-like antibodies. Taken together, these studies establish that PF4/heparin complexes are highly immunogenic and elicit self-reacting anti-PF4/heparin antibodies in a T cell-dependent manner... - In vivo efficacy of platelet-delivered, high specific activity factor VIII variantsTeshell K Greene
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
Blood 116:6114-22. 2010.... - Maturation stage-specific regulation of megakaryopoiesis by pointed-domain Ets proteinsLiyan Pang
Children s Hospital of Philadelphia, ARC 316H, 3165 Civic Center Blvd, Philadelphia, PA, USA
Blood 108:2198-206. 2006..In concert, these data reveal disparate, but overlapping, functions of Ets transcription factors at distinct stages of megakaryocyte maturation... - Transgenic mice studies demonstrate a role for platelet factor 4 in thrombosis: dissociation between anticoagulant and antithrombotic effect of heparinDon E Eslin
Division of Hematology, The Children s Hospital of Philadelphia, 34th Street and Civic Center Blvd, ARC Rm 316I, Philadelphia, PA 19104, USA
Blood 104:3173-80. 2004..The mechanisms underlying these observations of PF4 biology and their clinical implications remain to be determined... - Analysis of the spatial and temporal characteristics of platelet-delivered factor VIII-based clotsMichael Neyman
Division of Hematology, Children s Hospital of Philadelphia, PA 19104, USA
Blood 112:1101-8. 2008.... - Platelet factor 4 regulates megakaryopoiesis through low-density lipoprotein receptor-related protein 1 (LRP1) on megakaryocytesMichele P Lambert
Department of Pediatrics, Children s Hospital of Philadelphia, PA 19104, USA
Blood 114:2290-8. 2009.... - CXCL5 regulates chemokine scavenging and pulmonary host defense to bacterial infectionJunjie Mei
Division of Neonatology, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
Immunity 33:106-17. 2010..This study presents a paradigm whereby platelets and red cells alter chemokine scavenging and neutrophil-chemokine interaction during inflammation... - The kinetics of αIIbβ3 activation determines the size and stability of thrombi in mice: implications for antiplatelet therapyMoritz Stolla
Cardeza Foundation for Hematologic Research and Department of Medicine, Thomas Jefferson University, Philadelphia, PA, USA
Blood 117:1005-13. 2011.... - Targeting of a mutant plasminogen activator to circulating red blood cells for prophylactic fibrinolysisSergei Zaitsev
IFEM, University of Pennsylvania School of Medicine, One John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA 19104 6068, USA
J Pharmacol Exp Ther 332:1022-31. 2010..These results provide proof-of-principle for the development of a recombinant PA variant that binds to circulating RBC and provides thromboprophylaxis by use of a clinically relevant approach... - Antithrombotic thrombocytes: ectopic expression of urokinase-type plasminogen activator in plateletsDubravka Kufrin
Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, ARC; Rm 317, Philadelphia, PA 19104, USA
Blood 102:926-33. 2003..These studies show the feasibility of delivering fibrinolytic agents to sites of incipient thrombus formation through selective storage in platelets and offer a new strategy to prevent thrombosis and hemorrhage... - Platelet factor 4 localization in carotid atherosclerotic plaques: correlation with clinical parametersStephanie Pitsilos
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, 19104, USA
Thromb Haemost 90:1112-20. 2003..These studies support the rationale for the chronic use of anti-platelet therapy in patients at risk for developing symptomatic atherosclerosis... - The relative role of PLCbeta and PI3Kgamma in platelet activationLurong Lian
Department of Medicine of University of Pennsylvania, 421 Curie Blvd, Biomedical Research Bldg II III, Rm 912, Philadelphia, PA 19104, USA
Blood 106:110-7. 2005..Nonetheless, the diminished ability of knock-out platelets to normally spread after adhesion and to form stable thrombi in vivo suggests that both PLCbeta2/beta3 and PI3Kgamma play vital roles in platelet cytoskeletal dynamics... - Control of megakaryocyte-specific gene expression by GATA-1 and FOG-1: role of Ets transcription factorsXun Wang
University of Pennsylvania School of Medicine, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
EMBO J 21:5225-34. 2002..Our studies define a molecular context for transcriptional activation by GATA-1 and FOG-1, and may explain the occurrence of tandem GATA and Ets elements in the promoters of numerous megakaryocyte-expressed genes... - Defining a second epitope for heparin-induced thrombocytopenia/thrombosis antibodies using KKO, a murine HIT-like monoclonal antibodyZhong Q Li
Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia, USA
Blood 99:1230-6. 2002..Yet sites 1 and 2 can be recognized by distinct populations of antibodies. These studies further help to define a portion of the PF4 tetramer to which self-reactive antibodies develop in patients exposed to heparin... - Identification of distal regulatory regions in the human alpha IIb gene locus necessary for consistent, high-level megakaryocyte expressionMichael A Thornton
Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, USA
Blood 100:3588-96. 2002.... - Expression, purification and characterization of human glutamate dehydrogenase (GDH) allosteric regulatory mutationsJie Fang
Division of Endocrinology, The Children s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104, USA
Biochem J 363:81-7. 2002.... - Platelet factor 4 enhances the binding of oxidized low-density lipoprotein to vascular wall cellsTaher Nassar
Department of Clinical Biochemistry, The Center for Research, Prevention, and Treatment of Atherosclerosis, Hadassah University Hospital and Hebrew University Hadassah Medical School, Jerusalem 91120, Israel
J Biol Chem 278:6187-93. 2003.... - The role of surface PF4: glycosaminoglycan complexes in the pathogenesis of heparin-induced thrombocytopenia (HIT)Mortimer Poncz
University of Pennsylvania School of Medicine and The Children's Hospital of Philadelphia, USA
Pathophysiol Haemost Thromb 35:46-9. 2006 - Platelet factor 4 binds to low-density lipoprotein receptors and disrupts the endocytic machinery, resulting in retention of low-density lipoprotein on the cell surfaceBruce S Sachais
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104, USA
Blood 99:3613-22. 2002..Retention of LDL on cell surfaces may facilitate proatherogenic modifications and support an expanded role for platelets in the pathogenesis of atherosclerosis... - Platelet- and megakaryocyte-derived microparticles transfer CXCR4 receptor to CXCR4-null cells and make them susceptible to infection by X4-HIVTomasz Rozmyslowicz
Stem Cell Biology Program at James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky 40202, USA
AIDS 17:33-42. 2003..CONCLUSIONS: We postulate that both PMP and MegaMP may play a novel and important role in spreading HIV-1 infection by transferring the CXCR4 co-receptor to CD4+/CXCR4-null cells... - Heparin-induced thrombocytopenia: an autoimmune disorder regulated through dynamic autoantigen assembly/disassemblyDouglas B Cines
Department of Pathology and Laboratory Medicine, University of Pennsylvania, and Division of Hematology, Children s Hospital of Philadelphia 19104, USA
J Clin Apher 22:31-6. 2007..They also demonstrate that this autoimmune disease can be modulated at the level of autoantigen formation and point to rational means to intervene proximal to thrombin generation... - Cyclin D-Cdk4 is regulated by GATA-1 and required for megakaryocyte growth and polyploidizationAndrew G Muntean
Graduate Program in Molecular Genetics and Cell Biology, University of Chicago, IL, USA
Blood 109:5199-207. 2007..Together, these data show that GATA-1 controls growth and polyploidization by regulating cyclin D-Cdk4 kinase activity...
Research Grants
- Etiologic and therapeutic studies of heparin-induced thrombocytopenia (HIT)Mortimer Poncz; Fiscal Year: 2007....
- Fluorescent Microscope for Thrombosis StudiesMortimer Poncz; Fiscal Year: 2003....
- MOLECULAR BASIS OF HEPARIN ASSOCIATED THROMBOCYTOPENIAMortimer Poncz; Fiscal Year: 1999..This in turn could lead to the finding of anti- idiotype antibodies of diagnostic and perhaps therapeutic usefulness. ..
- Etiologic and therapeutic studies of heparin-induced thrombocytopenia (HIT)Mortimer Poncz; Fiscal Year: 2011..abstract_text> ..