Mortimer Poncz

Summary

Affiliation: The Children's Hospital of Philadelphia
Country: USA

Publications

  1. ncbi request reprint Intracellular interaction of von Willebrand factor and factor VIII depends on cellular context: lessons from platelet-expressed factor VIII
    Helen Yarovoi
    Department of Pediatrics, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Blood 105:4674-6. 2005
  2. pmc Infusion of mature megakaryocytes into mice yields functional platelets
    Rudy Fuentes
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    J Clin Invest 120:3917-22. 2010
  3. ncbi request reprint Mechanistic basis of heparin-induced thrombocytopenia
    Mortimer 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
  4. pmc Megakaryocyte biology and related disorders
    Liyan 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
  5. pmc Targeting recombinant thrombomodulin fusion protein to red blood cells provides multifaceted thromboprophylaxis
    Sergei 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
  6. pmc Monocyte-bound PF4 in the pathogenesis of heparin-induced thrombocytopenia
    Lubica Rauova
    Department of Pediatrics, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Blood 116:5021-31. 2010
  7. pmc Pleiotropic platelet defects in mice with disrupted FOG1-NuRD interaction
    Yuhuan Wang
    Division of Hematology, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Blood 118:6183-91. 2011
  8. pmc NuRD mediates activating and repressive functions of GATA-1 and FOG-1 during blood development
    Annarita Miccio
    Division of Hematology, The Children s Hospital of Philadelphia, Philadelphia, PA, USA
    EMBO J 29:442-56. 2010
  9. pmc Dynamic antibody-binding properties in the pathogenesis of HIT
    Bruce S Sachais
    Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Blood 120:1137-42. 2012
  10. pmc Sustained thromboprophylaxis mediated by an RBC-targeted pro-urokinase zymogen activated at the site of clot formation
    Sergei 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

Detail Information

Publications48

  1. ncbi request reprint Intracellular interaction of von Willebrand factor and factor VIII depends on cellular context: lessons from platelet-expressed factor VIII
    Helen 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...
  2. pmc Infusion of mature megakaryocytes into mice yields functional platelets
    Rudy 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...
  3. ncbi request reprint Mechanistic basis of heparin-induced thrombocytopenia
    Mortimer 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...
  4. pmc Megakaryocyte biology and related disorders
    Liyan 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...
  5. pmc Targeting recombinant thrombomodulin fusion protein to red blood cells provides multifaceted thromboprophylaxis
    Sergei 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...
  6. pmc Monocyte-bound PF4 in the pathogenesis of heparin-induced thrombocytopenia
    Lubica Rauova
    Department of Pediatrics, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Blood 116:5021-31. 2010
    ....
  7. pmc Pleiotropic platelet defects in mice with disrupted FOG1-NuRD interaction
    Yuhuan Wang
    Division of Hematology, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Blood 118:6183-91. 2011
    ....
  8. pmc NuRD mediates activating and repressive functions of GATA-1 and FOG-1 during blood development
    Annarita 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...
  9. pmc Dynamic antibody-binding properties in the pathogenesis of HIT
    Bruce 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...
  10. pmc Sustained thromboprophylaxis mediated by an RBC-targeted pro-urokinase zymogen activated at the site of clot formation
    Sergei 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...
  11. pmc Role of platelet surface PF4 antigenic complexes in heparin-induced thrombocytopenia pathogenesis: diagnostic and therapeutic implications
    Lubica 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...
  12. pmc Antibodies associated with heparin-induced thrombocytopenia (HIT) inhibit activated protein C generation: new insights into the prothrombotic nature of HIT
    M 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...
  13. pmc The role of platelet factor 4 in radiation-induced thrombocytopenia
    Michele 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...
  14. pmc FOG1 requires NuRD to promote hematopoiesis and maintain lineage fidelity within the megakaryocytic-erythroid compartment
    Gregory 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...
  15. doi request reprint Role of the platelet chemokine platelet factor 4 (PF4) in hemostasis and thrombosis
    M 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
    ....
  16. pmc SLC35D3 delivery from megakaryocyte early endosomes is required for platelet dense granule biogenesis and is differentially defective in Hermansky-Pudlak syndrome models
    Ronghua 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
    ....
  17. pmc 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 propeller
    Ramesh 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...
  18. ncbi request reprint Ultralarge complexes of PF4 and heparin are central to the pathogenesis of heparin-induced thrombocytopenia
    Lubica Rauova
    Division of Hematology, Children s Hospital of Philadelphia, PA, USA
    Blood 105:131-8. 2005
    ....
  19. ncbi request reprint Interactions of platelet factor 4 with the vessel wall
    Bruce 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...
  20. ncbi request reprint Factor VIII ectopically expressed in platelets: efficacy in hemophilia A treatment
    Helen 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...
  21. pmc Platelet factor 4 is a negative autocrine in vivo regulator of megakaryopoiesis: clinical and therapeutic implications
    Michele 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...
  22. pmc In vivo efficacy of platelet-delivered, high specific activity factor VIII variants
    Teshell K Greene
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    Blood 116:6114-22. 2010
    ....
  23. pmc Determinants of PF4/heparin immunogenicity
    Shayela Suvarna
    Division of Hematology, Duke University Medical Center, Durham, NC 27710, USA
    Blood 110:4253-60. 2007
    ....
  24. pmc Endogenous platelet factor 4 stimulates activated protein C generation in vivo and improves survival after thrombin or lipopolysaccharide challenge
    M 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...
  25. ncbi request reprint Transgenic mice studies demonstrate a role for platelet factor 4 in thrombosis: dissociation between anticoagulant and antithrombotic effect of heparin
    Don 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...
  26. pmc PF4/heparin complexes are T cell-dependent antigens
    Shayela 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...
  27. pmc Maturation stage-specific regulation of megakaryopoiesis by pointed-domain Ets proteins
    Liyan 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...
  28. pmc Minimal modification in the factor VIII B-domain sequence ameliorates the murine hemophilia A phenotype
    Joshua I Siner
    Division of Hematology, The Children s Hospital of Philadelphia, Philadelphia, PA and
    Blood 121:4396-403. 2013
    ..Thus, FVIII-RH is an attractive bioengineered molecule for improving efficacy without increased immunogenicity and may be suitable for both protein- and gene-based strategies for HA...
  29. pmc Analysis of the spatial and temporal characteristics of platelet-delivered factor VIII-based clots
    Michael Neyman
    Division of Hematology, Children s Hospital of Philadelphia, PA 19104, USA
    Blood 112:1101-8. 2008
    ....
  30. pmc Platelet factor 4 regulates megakaryopoiesis through low-density lipoprotein receptor-related protein 1 (LRP1) on megakaryocytes
    Michele P Lambert
    Department of Pediatrics, Children s Hospital of Philadelphia, PA 19104, USA
    Blood 114:2290-8. 2009
    ....
  31. pmc CXCL5 regulates chemokine scavenging and pulmonary host defense to bacterial infection
    Junjie 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...
  32. pmc The kinetics of αIIbβ3 activation determines the size and stability of thrombi in mice: implications for antiplatelet therapy
    Moritz Stolla
    Cardeza Foundation for Hematologic Research and Department of Medicine, Thomas Jefferson University, Philadelphia, PA, USA
    Blood 117:1005-13. 2011
    ....
  33. pmc Targeting of a mutant plasminogen activator to circulating red blood cells for prophylactic fibrinolysis
    Sergei 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...
  34. doi request reprint Challenges and promises for the development of donor-independent platelet transfusions
    Michele P Lambert
    Division of Hematology, The Children s Hospital of Philadelphia, Philadelphia, PA
    Blood 121:3319-24. 2013
    ....
  35. pmc The relative role of PLCbeta and PI3Kgamma in platelet activation
    Lurong 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...
  36. ncbi request reprint Platelet factor 4 localization in carotid atherosclerotic plaques: correlation with clinical parameters
    Stephanie 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...
  37. ncbi request reprint Antithrombotic thrombocytes: ectopic expression of urokinase-type plasminogen activator in platelets
    Dubravka 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...
  38. pmc Control of megakaryocyte-specific gene expression by GATA-1 and FOG-1: role of Ets transcription factors
    Xun 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...
  39. pmc Platelet factor 4 activity against P. falciparum and its translation to nonpeptidic mimics as antimalarials
    Melissa S Love
    Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Cell Host Microbe 12:815-23. 2012
    ..Lead smHDPs also reduced parasitemia in a murine malaria model. Thus, identifying host molecules that control parasite growth can further the development of related molecules with therapeutic potential...
  40. ncbi request reprint Defining a second epitope for heparin-induced thrombocytopenia/thrombosis antibodies using KKO, a murine HIT-like monoclonal antibody
    Zhong 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...
  41. ncbi request reprint Identification of distal regulatory regions in the human alpha IIb gene locus necessary for consistent, high-level megakaryocyte expression
    Michael A Thornton
    Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, USA
    Blood 100:3588-96. 2002
    ....
  42. pmc Expression, purification and characterization of human glutamate dehydrogenase (GDH) allosteric regulatory mutations
    Jie 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
    ....
  43. ncbi request reprint Platelet factor 4 enhances the binding of oxidized low-density lipoprotein to vascular wall cells
    Taher 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
    ....
  44. ncbi request reprint 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
  45. ncbi request reprint Platelet factor 4 binds to low-density lipoprotein receptors and disrupts the endocytic machinery, resulting in retention of low-density lipoprotein on the cell surface
    Bruce 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...
  46. ncbi request reprint Heparin-induced thrombocytopenia: an autoimmune disorder regulated through dynamic autoantigen assembly/disassembly
    Douglas 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...
  47. ncbi request reprint Platelet- and megakaryocyte-derived microparticles transfer CXCR4 receptor to CXCR4-null cells and make them susceptible to infection by X4-HIV
    Tomasz Rozmyslowicz
    Stem Cell Biology Program at James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky 40202, USA
    AIDS 17:33-42. 2003
    ..We found that peripheral blood platelet- (PMP) and megakaryocyte-derived MP (MegaMP) that highly express CXCR4 may transfer this receptor from the surface of platelets or megakaryocytes to the surface of CXCR4-null cells...
  48. pmc Cyclin D-Cdk4 is regulated by GATA-1 and required for megakaryocyte growth and polyploidization
    Andrew 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 Grants16

  1. Etiologic and therapeutic studies of heparin-induced thrombocytopenia (HIT)
    Mortimer Poncz; Fiscal Year: 2007
    ....
  2. Fluorescent Microscope for Thrombosis Studies
    Mortimer Poncz; Fiscal Year: 2003
    ....
  3. MOLECULAR BASIS OF HEPARIN ASSOCIATED THROMBOCYTOPENIA
    Mortimer Poncz; Fiscal Year: 1999
    ..This in turn could lead to the finding of anti- idiotype antibodies of diagnostic and perhaps therapeutic usefulness. ..
  4. Etiologic and therapeutic studies of heparin-induced thrombocytopenia (HIT)
    Mortimer Poncz; Fiscal Year: 2011
    ..abstract_text> ..