Douglas Cines

Summary

Affiliation: University of Pennsylvania
Country: USA

Publications

  1. ncbi request reprint Pathogenesis of immune thrombocytopenia
    Douglas B Cines
    PERELMAN UNIVERSITY OF PENNSYLVANIA SCHOOL OF MEDICINE, Department of Pathology and Laboratory Medicine, 513A Stellar Chance Pavilion, 422, Curie Boulevard, Philadelphia, PA 19104, United States Electronic address
    Presse Med 43:e49-59. 2014
  2. doi request reprint Clinical trial opportunities in hemostasis and thrombosis: NHBLI State-of-the-Science symposium
    Douglas B Cines
    Department of Pathology and Laboratory Medicine and Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Am J Hematol 87:235-8. 2012
  3. pmc Antigen and substrate withdrawal in the management of autoimmune thrombotic disorders
    Douglas B Cines
    Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 4274, USA
    Blood 120:4134-42. 2012
  4. ncbi request reprint Mechanisms of action of therapeutics in idiopathic thrombocytopenic purpura
    Douglas B Cines
    University of Pennsylvania School of Medicine, Department of Pathology and Laboratory Medicine, 513A Stellar Chance, 422 Curie Boulevard, Philadelphia, PA 19104, USA
    J Pediatr Hematol Oncol 25:S52-6. 2003
  5. pmc Pathobiology of secondary immune thrombocytopenia
    Douglas B Cines
    University of Pennsylvania School of Medicine, Department of Pathology and Laboratory Medicine, Philadelphia, PA 19104, USA
    Semin Hematol 46:S2-14. 2009
  6. doi request reprint Romiplostim
    Douglas B Cines
    Douglas B Cines is in the Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Nat Rev Drug Discov 7:887-8. 2008
  7. ncbi request reprint Pathogenesis of chronic immune thrombocytopenic purpura
    Douglas B Cines
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Curr Opin Hematol 14:511-4. 2007
  8. ncbi request reprint Management of adult idiopathic thrombocytopenic purpura
    Douglas B Cines
    Department of Pathology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Annu Rev Med 56:425-42. 2005
  9. 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
  10. ncbi request reprint How I treat idiopathic thrombocytopenic purpura (ITP)
    Douglas B Cines
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Blood 106:2244-51. 2005

Research Grants

Detail Information

Publications79

  1. ncbi request reprint Pathogenesis of immune thrombocytopenia
    Douglas B Cines
    PERELMAN UNIVERSITY OF PENNSYLVANIA SCHOOL OF MEDICINE, Department of Pathology and Laboratory Medicine, 513A Stellar Chance Pavilion, 422, Curie Boulevard, Philadelphia, PA 19104, United States Electronic address
    Presse Med 43:e49-59. 2014
    ..This chapter surveys key new insights into the pathogenesis of ITP and attempts to integrate them into a model that may serve as a template for future investigation. ..
  2. doi request reprint Clinical trial opportunities in hemostasis and thrombosis: NHBLI State-of-the-Science symposium
    Douglas B Cines
    Department of Pathology and Laboratory Medicine and Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Am J Hematol 87:235-8. 2012
    ....
  3. pmc Antigen and substrate withdrawal in the management of autoimmune thrombotic disorders
    Douglas B Cines
    Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 4274, USA
    Blood 120:4134-42. 2012
    ....
  4. ncbi request reprint Mechanisms of action of therapeutics in idiopathic thrombocytopenic purpura
    Douglas B Cines
    University of Pennsylvania School of Medicine, Department of Pathology and Laboratory Medicine, 513A Stellar Chance, 422 Curie Boulevard, Philadelphia, PA 19104, USA
    J Pediatr Hematol Oncol 25:S52-6. 2003
    ..Rationale therapy awaits a more thorough understanding of autoantibody production...
  5. pmc Pathobiology of secondary immune thrombocytopenia
    Douglas B Cines
    University of Pennsylvania School of Medicine, Department of Pathology and Laboratory Medicine, Philadelphia, PA 19104, USA
    Semin Hematol 46:S2-14. 2009
    ..This thrombocytopenia may be caused by cross-reacting antibodies and closely mimics acute ITP of childhood. Proper diagnosis and treatment of the underlying disorder, where necessary, play an important role in patient management...
  6. doi request reprint Romiplostim
    Douglas B Cines
    Douglas B Cines is in the Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Nat Rev Drug Discov 7:887-8. 2008
    ....
  7. ncbi request reprint Pathogenesis of chronic immune thrombocytopenic purpura
    Douglas B Cines
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Curr Opin Hematol 14:511-4. 2007
    ..This article summarizes recent insights into the pathophysiology of immune thrombocytopenic purpura, a disorder in which autoantibodies against cell-specific glycoproteins (GPIIb-IIIa, GPIb-IX and others) accelerate platelet destruction...
  8. ncbi request reprint Management of adult idiopathic thrombocytopenic purpura
    Douglas B Cines
    Department of Pathology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Annu Rev Med 56:425-42. 2005
    ..This article focuses on the management of primary ITP in adults. We discuss criteria for treatment, the roles of splenectomy and other treatment options along with their side effects, and the management of ITP during pregnancy...
  9. 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...
  10. ncbi request reprint How I treat idiopathic thrombocytopenic purpura (ITP)
    Douglas B Cines
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Blood 106:2244-51. 2005
  11. pmc The ITP syndrome: pathogenic and clinical diversity
    Douglas B Cines
    Department of Pathology and Laboratory Medicine, University of Pennsylvania, 513A Stellar Chance, 422 Curie Blvd, Philadelphia, PA 19104, USA
    Blood 113:6511-21. 2009
    ..Better understanding of pathogenesis and tolerance checkpoint defects leading to autoantibody formation may facilitate patient-specific approaches to diagnosis and management...
  12. pmc Inhibition of integrin alphavbeta3 prevents urokinase plasminogen activator-mediated impairment of cerebrovasodilation after cerebral hypoxia/ischemia
    J Willis Kiessling
    Dept of Anesthesiology and Critical Care, 3620 Hamilton Walk, JM3, Univ of Pennsylvania, Philadelphia, PA l9l04, USA
    Am J Physiol Heart Circ Physiol 296:H862-7. 2009
    ..These data suggest that the inhibition of uPA and integrin signaling may preserve cerebrohemodynamic control after H/I...
  13. 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...
  14. ncbi request reprint Neutralizing the neurotoxic effects of exogenous and endogenous tPA
    William M Armstead
    Department of Anesthesiology, University of Pennsylvania, 3620 Hamilton Walk, JM3, Philadelphia, Pennsylvania 19104, USA
    Nat Neurosci 9:1150-5. 2006
    ..These experiments suggest mechanisms to reduce the neurotoxic effects of tPA without compromising its fibrinolytic activity, through the use of selective antagonists and new tPA formulations...
  15. ncbi request reprint Genetic analysis of autoantibodies in idiopathic thrombocytopenic purpura reveals evidence of clonal expansion and somatic mutation
    Jessica H Roark
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA
    Blood 100:1388-98. 2002
    ..The extraordinarily high usage of the V(H)3-30 heavy-chain gene in these patients has implications for the pathogenesis, diagnosis, and management of chronic ITP...
  16. ncbi request reprint The kringle stabilizes urokinase binding to the urokinase receptor
    Khalil Bdeir
    Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Blood 102:3600-8. 2003
    ..These data demonstrate an important role for the kringle in stabilizing the binding of scuPA to uPAR...
  17. ncbi request reprint Blood clearance and activity of erythrocyte-coupled fibrinolytics
    Kumkum Ganguly
    IFEM, University of Pennsylvania School of Medicine, One John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA 19104 6068, USA
    J Pharmacol Exp Ther 312:1106-13. 2005
    ..g., loss of cofactor stimulation). These factors, different from those guiding the design of soluble PA for lysis of existing clots, can be exploited in the rational design of RBC/PA tailored for specific prophylactic indications...
  18. 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...
  19. pmc Regulation of airway contractility by plasminogen activators through N-methyl-D-aspartate receptor-1
    Taher Nassar
    Department of Pathology and Laboratory Medicine, University of Pennsylvania, 513A Stellar Chance, 422 Curie Boulevard, Philadelphia, PA 19104, USA
    Am J Respir Cell Mol Biol 43:703-11. 2010
    ..These studies identify involvement of PAs and NMDA-R1 in airway contractility, and define new loci that could lead to the development of novel interventions for reactive airway disease...
  20. 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...
  21. pmc Red blood cells-coupled tPA prevents impairment of cerebral vasodilatory responses and tissue injury in pediatric cerebral hypoxia/ischemia through inhibition of ERK MAPK activation
    William M Armstead
    Department of Anesthesiology and Critical Care, 3620 Hamilton Walk, JM3, University of Pennsylvania, Philadelphia, PA l9l04, USA
    J Cereb Blood Flow Metab 29:1463-74. 2009
    ..These data suggest that coupling of tPA to RBCs offers a novel approach toward increasing the benefit/risk ratio of thrombolytic therapy for CNS disorders associated with H/I...
  22. pmc Signaling, delivery and age as emerging issues in the benefit/risk ratio outcome of tPA For treatment of CNS ischemic disorders
    William M Armstead
    Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Neurochem 113:303-12. 2010
    ..Additionally, the role of age will be considered since thrombolytic therapy is being increasingly used in the pediatric population, but there are few basic science studies of CNS injury in pediatric animals...
  23. ncbi request reprint Safety of the thrombopoiesis-stimulating agents for the treatment of immune thrombocytopenia
    Adam Cuker
    Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    Curr Drug Saf 5:171-81. 2010
    ..The incidence and severity of these toxicities as well as strategies for monitoring patient safety and pharmacovigilance are discussed...
  24. ncbi request reprint Delivery of anti-platelet-endothelial cell adhesion molecule single-chain variable fragment-urokinase fusion protein to the cerebral vasculature lyses arterial clots and attenuates postischemic brain edema
    Kristina Danielyan
    Department of Pharmacology and Targeted Therapeutics Program, Institute of Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104 6068, USA
    J Pharmacol Exp Ther 321:947-52. 2007
    ..Effective and safe thromboprophylaxis in the cerebral arterial circulation by anti-PECAM scFv-uPA represents a prototype of a new paradigm to prevent recurrent cerebrovascular thrombosis...
  25. pmc Novel plasminogen activator inhibitor-1-derived peptide protects against impairment of cerebrovasodilation after photothrombosis through inhibition of JNK MAPK
    William M Armstead
    Dept of Anesthesiology and Critical Care, 3620 Hamilton Walk, JM3, Univ of Pennsylvania, Philadelphia, PA 19104, USA
    Am J Physiol Regul Integr Comp Physiol 299:R480-5. 2010
    ..JNK MAPK inhibitors, including PAI-1-DP, may offer a novel approach to increase the benefit-to-risk ratio of thrombolytic therapy and enable its use in central nervous system ischemic disorders...
  26. pmc Erythrocyte-bound tissue plasminogen activator is neuroprotective in experimental traumatic brain injury
    Sherman C Stein
    Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19106, USA
    J Neurotrauma 26:1585-92. 2009
    ..01) and hippocampal cell loss ( p<0.01) in the RBC=tPA group than in all other groups. These results reveal that RBC/tPA is more neuroprotective in experimental TBI than is unbound tPA...
  27. pmc PAI-1-derived peptide EEIIMD prevents impairment of cerebrovasodilation by augmenting p38 MAPK upregulation after cerebral hypoxia/ischemia
    William M Armstead
    Department of Anesthesiology and Critical Care, University of Pennsylvania, 3620 Hamilton Walk, Philadelphia, PA 19104, USA
    Am J Physiol Heart Circ Physiol 299:H76-80. 2010
    ....
  28. pmc Prophylactic thrombolysis by thrombin-activated latent prourokinase targeted to PECAM-1 in the pulmonary vasculature
    Bi Sen Ding
    Department of Pharmacology, Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, USA
    Blood 111:1999-2006. 2008
    ..Endothelium-targeted thromboprophylaxis triggered by a prothrombotic enzyme illustrates a novel approach to time- and site-specific regulation of proteolytic reactions that can be modulated for therapeutic benefit...
  29. 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...
  30. pmc uPA impairs cerebrovasodilation after hypoxia/ischemia through LRP and ERK MAPK
    William M Armstead
    Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA 19104, USA
    Brain Res 1231:121-31. 2008
    ..These data suggest that modulation of uPA upregulation and/or uPA-mediated signal transduction may preserve cerebrohemodynamic control after hypoxia/ischemia...
  31. 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...
  32. pmc uPA modulates the age-dependent effect of brain injury on cerebral hemodynamics through LRP and ERK MAPK
    William M Armstead
    Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Cereb Blood Flow Metab 29:524-33. 2009
    ..These data indicate that uPA is upregulated after FPI and produces an age-dependent early hyperemia followed by histopathology through an LRP- and ERK MAPK-dependent pathway...
  33. pmc Urokinase plasminogen activator impairs SNP and PGE2 cerebrovasodilation after brain injury through activation of LRP and ERK MAPK
    William M Armstead
    Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Neurotrauma 25:1375-81. 2008
    ..These data indicate that uPA contributes to the impairment of SNP and PGE(2)-mediated cerebrovasodilation seen after brain injury through activation of LRP and ERK MAPK...
  34. pmc Nuclear translocation of urokinase-type plasminogen activator
    Victoria Stepanova
    Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104, USA
    Blood 112:100-10. 2008
    ..These data reveal a novel pathway by which uPA is rapidly translocated to the nucleus where it might participate in regulating gene expression...
  35. ncbi request reprint Altered NO function contributes to impairment of uPA and tPA cerebrovasodilation after brain injury
    William M Armstead
    Departments of Anesthesia and Pharmacology, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA
    J Neurotrauma 21:1204-11. 2004
    ..FPI blunted uPA and tPA induced pial artery dilation as well as the associated release of cGMP. These data suggest therefore that altered NO function contributes to the impairment of uPA and tPA cerebrovasodilation after brain injury...
  36. ncbi request reprint Regulation of the single-chain urokinase-urokinase receptor complex activity by plasminogen and fibrin: novel mechanism of fibrin specificity
    Abd Al Roof Higazi
    Department of Pathology and Laboratory Medicine, 513A Stellar Chance, 422 Curie Blvd, University of Pennsylvania, Philadelphia, PA, 19104, USA
    Blood 105:1021-8. 2005
    ..These studies provide insight into the regulation of uPA-mediated plasminogen activation and identify a novel mechanism for its fibrin specificity...
  37. 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...
  38. ncbi request reprint Thrombocytopenia after treatment with platelet glycoprotein IIb/IIIa inhibitors
    Charles S Abrams
    Hematology Oncology Division, University of Pennsylvania, 421 Curie Boulevard, Basic Research Building II III, Room 912, Philadelphia, PA 19104, USA
    Curr Hematol Rep 3:143-7. 2004
    ..Screening for the development of these antibodies may reduce the incidence of thrombocytopenia associated with these agents, but it may limit their chronic usage...
  39. ncbi request reprint Plasminogen activators contribute to age-dependent impairment of NMDA cerebrovasodilation after brain injury
    William M Armstead
    Department of Anesthesia, University of Pennsylvania, Philadelphia, PA 19104, USA
    Brain Res Dev Brain Res 156:139-46. 2005
    ..EEIIMD and suPAR are efficacious and selective inhibitors of plasminogen activator induced dilation. These data suggest that plasminogen activators contribute to age-dependent impairment of NMDA induced dilation following FPI...
  40. ncbi request reprint Platelets inhibit the lysis of pulmonary microemboli
    Juan Carlos Murciano
    Institute for Environmental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Am J Physiol Lung Cell Mol Physiol 282:L529-39. 2002
    ..These studies show that platelets suppress pulmonary fibrinolysis. The mechanism(s) by which platelets stabilize ME and utility of platelet inhibitors to facilitate their dissolution deserves further study...
  41. ncbi request reprint ICAM-directed vascular immunotargeting of antithrombotic agents to the endothelial luminal surface
    Juan Carlos Murciano
    Institute of Environmental Medicine, Department of Pharmacology, University of Pennsylvania, Philadelphia, PA, USA
    Blood 101:3977-84. 2003
    ..Enhanced drug delivery to sites of inflammation and the potential anti-inflammatory effect of blocking ICAM-1 may enhance the benefit of this targeting strategy...
  42. ncbi request reprint Platelet glycoprotein IIb/IIIa inhibitors and thrombocytopenia: possible link between platelet activation, autoimmunity and thrombosis
    Charles S Abrams
    Hematology Oncology Division, University of Pennsylvania, Philadelphia 19104 4283, USA
    Thromb Haemost 88:888-9. 2002
  43. 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...
  44. ncbi request reprint Plasminogen activators contribute to impairment of hypercapnic and hypotensive cerebrovasodilation after cerebral hypoxia/ischemia in the newborn pig
    William M Armstead
    Department of Anesthesia, University of Pennsylvania, Philadelphia, PA 19104, USA
    Stroke 36:2265-9. 2005
    ..We investigated the role of exogenous and endogenous plasminogen activators (PA) in piglet hypercapnic and hypotensive dilator impairment after H/I...
  45. doi request reprint Evidence-based mini-review: Is indium-labeled autologous platelet scanning predictive of response to splenectomy in patients with chronic immune thrombocytopenia?
    Adam Cuker
    Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Hematology Am Soc Hematol Educ Program 2010:385-6. 2010
    ..The patient asks if there are any means by which to predict likelihood of response to splenectomy. You have heard about the use of indium-labeled autologous platelet scanning for this purpose and wonder what the evidence shows...
  46. doi request reprint Immune thrombocytopenia
    Adam Cuker
    Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Hematology Am Soc Hematol Educ Program 2010:377-84. 2010
    ..Recent studies suggest the potential for aggressive therapy at the time of diagnosis to alter the natural history of ITP and point to the importance of quality-of-life considerations in therapeutic decision making...
  47. pmc tPA contributes to impairment of ATP and Ca sensitive K channel mediated cerebrovasodilation after hypoxia/ischemia through upregulation of ERK MAPK
    William M Armstead
    Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA l9l04, USA
    Brain Res 1376:88-93. 2011
    ..These data suggest that thrombolytic therapy for treatment of CNS ischemic disorders can dysregulate cerebrohemodynamics by impairing cation-mediated control of cerebrovascular tone...
  48. 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...
  49. ncbi request reprint Prophylactic fibrinolysis through selective dissolution of nascent clots by tPA-carrying erythrocytes
    Juan Carlos Murciano
    Institute for Environmental Medicine, University of Pennsylvania, 3620 Hamilton Walk, Philadelphia, Pennsylvania 19104, USA
    Nat Biotechnol 21:891-6. 2003
    ..This RBC-based drug delivery strategy alters the fibrinolytic profile of tPA, permitting prophylactic fibrinolysis...
  50. 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...
  51. ncbi request reprint Immune thrombocytopenic purpura
    Douglas B Cines
    Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, USA
    N Engl J Med 346:995-1008. 2002
  52. ncbi request reprint Fibrin affinity of erythrocyte-coupled tissue-type plasminogen activators endures hemodynamic forces and enhances fibrinolysis in vivo
    Kumkum Ganguly
    Institute for Environmental Medicine, University of Pennsylvania School of Medicine, One John Morgan Bldg, 3620 Hamilton Walk, Philadelphia, PA 19104 6068, USA
    J Pharmacol Exp Ther 316:1130-6. 2006
    ..Behavior of RBC/PAs under hemodynamic pressure is an important predictor of their performance in vivo...
  53. pmc Human complement receptor type 1-directed loading of tissue plasminogen activator on circulating erythrocytes for prophylactic fibrinolysis
    Sergei Zaitsev
    Institute for Environmental Medicine, 1 John Morgan Bldg, University of Pennsylvania Medical Center, 3620 Hamilton Walk, Philadelphia, PA 19104 6068, USA
    Blood 108:1895-902. 2006
    ..CR1-directed immunotargeting of PAs to circulating RBCs provides a safe and practical means to deliver fibrinolytics for thromboprophylaxis in settings characterized by a high imminent risk of thrombosis...
  54. pmc Endothelial targeting of a recombinant construct fusing a PECAM-1 single-chain variable antibody fragment (scFv) with prourokinase facilitates prophylactic thrombolysis in the pulmonary vasculature
    Bi Sen Ding
    Department of Pharmacology, IFEM, 1 John Morgan Bldg, University of Pennsylvania, 3620 Hamilton Walk, Philadelphia, PA 19104 6068, USA
    Blood 106:4191-8. 2005
    ....
  55. pmc Cerebrovascular thromboprophylaxis in mice by erythrocyte-coupled tissue-type plasminogen activator
    Kristina Danielyan
    Pharmacology Department, Universityof Pennsylvania, Philadelphia, PA 19104 6068, USA
    Circulation 118:1442-9. 2008
    ..To evaluate the utility of this new approach for preventing cerebrovascular thrombosis, we examined the effect of RBC/tPA in animal models of cerebrovascular thromboembolism and ischemia...
  56. ncbi request reprint The glycocalyx protects erythrocyte-bound tissue-type plasminogen activator from enzymatic inhibition
    Kumkum Ganguly
    Institute for Environmental Medicine, University of Pennsylvania Medical Center, 3620 Hamilton Walk, Philadelphia, PA 19104 6068, USA
    J Pharmacol Exp Ther 321:158-64. 2007
    ..Thus, the RBC glycocalyx protects RBC-coupled tPA against inhibition. Resistance to high levels of inhibitors in vivo contributes to the potential utility of RBC/tPA for thromboprophylaxis...
  57. pmc Anchoring fusion thrombomodulin to the endothelial lumen protects against injury-induced lung thrombosis and inflammation
    Bi Sen Ding
    Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Am J Respir Crit Care Med 180:247-56. 2009
    ..Diverse forms of pulmonary and vascular injury are accompanied by down-regulation of TM, which aggravates tissue injury. We postulated that anchoring TM to the endothelial surface would restore its protective functions...
  58. ncbi request reprint The immune thrombocytopenia syndrome: a disorder of diverse pathogenesis and clinical presentation
    Douglas B Cines
    Department of Medicine and Pathology, University of Pennsylvania, Philadelphia, PA, USA
    Hematol Oncol Clin North Am 23:1155-61. 2009
    ....
  59. ncbi request reprint Direct interaction of the kringle domain of urokinase-type plasminogen activator (uPA) and integrin alpha v beta 3 induces signal transduction and enhances plasminogen activation
    Takehiko Tarui
    Department of Dermatology, UC Davis Medical Center, Research III, Sacramento, CA 95817, USA
    Thromb Haemost 95:524-34. 2006
    ..The uPA kringle-integrin interaction may represent a novel therapeutic target for cancer, inflammation, and vascular remodeling...
  60. ncbi request reprint Critical role of integrin alpha 5 beta 1 in urokinase (uPA)/urokinase receptor (uPAR, CD87) signaling
    Takehiko Tarui
    Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 278:29863-72. 2003
    ..uPAR complex to alpha 5 beta 1 via uPAR, and (c) signal transduction through alpha 5 beta 1...
  61. 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
  62. ncbi request reprint Urokinase induces activation of STAT3 in lung epithelial cells
    Sreerama Shetty
    Department of Specialty Care Services, The University of Texas Health Center at Tyler, 11937 U S Highway 271, Tyler, TX 75708, USA
    Am J Physiol Lung Cell Mol Physiol 291:L772-80. 2006
    ....
  63. ncbi request reprint Binding of urokinase to low density lipoprotein-related receptor (LRP) regulates vascular smooth muscle cell contraction
    Taher Nassar
    Department of Clinical Biochemistry, Hadassah University Hospital and Hebrew University Hadassah Medical School, Jerusalem 91120, Israel
    J Biol Chem 277:40499-504. 2002
    ..These studies identify a novel signal transducing cellular receptor pathway involved in the regulation of vascular contractility...
  64. pmc Structural basis of interaction between urokinase-type plasminogen activator and its receptor
    Cyril Barinka
    Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA
    J Mol Biol 363:482-95. 2006
    ....
  65. ncbi request reprint LRP and alphavbeta3 mediate tPA activation of smooth muscle cells
    Sa ed Akkawi
    Department of Clinical Biochemistry, and Interdepartmental Unit, Hadassah University Hospital and Hebrew University Hadassah Medical School, Jerusalem, Israel
    Am J Physiol Heart Circ Physiol 291:H1351-9. 2006
    ..Delineating the mechanism underlying these interactions and the nature of the signals transduced may provide new tools to regulate vascular tone and other consequences of tPA-mediated signaling...
  66. ncbi request reprint Structure of human urokinase plasminogen activator in complex with its receptor
    Qing Huai
    Division of Hemostasis and Thrombosis, Center for Vascular Biology Research, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
    Science 311:656-9. 2006
    ..The structure provides insight into the flexibility of the urokinase receptor that enables its interaction with a wide variety of ligands and a basis for the design of urokinase-urokinase receptor antagonists...
  67. pmc Determinants of PF4/heparin immunogenicity
    Shayela Suvarna
    Division of Hematology, Duke University Medical Center, Durham, NC 27710, USA
    Blood 110:4253-60. 2007
    ....
  68. ncbi request reprint Induction of plasminogen activator inhibitor-1 by urokinase in lung epithelial cells
    Sreerama Shetty
    Department of Specialty Care Services, University of Texas Health Center, Tyler, Texas 75708, USA
    J Biol Chem 278:18124-31. 2003
    ..Induction of PAI-1 by exposure of lung epithelial cells to uPA is a newly recognized pathway by which PAI-1 could regulate local fibrinolysis and urokinase-dependent cellular responses in the setting of lung inflammation or neoplasia...
  69. 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...
  70. 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
    ....
  71. ncbi request reprint Crystallization of soluble urokinase receptor (suPAR) in complex with urokinase amino-terminal fragment (1-143)
    Mingdong Huang
    State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, People s Republic of China
    Acta Crystallogr D Biol Crystallogr 61:697-700. 2005
    ..It is shown that uPA is capable of dissociating the oligomerization of suPAR and the crystallization of the suPAR-ATF complex is reported here. The resulting crystals diffract to 3.1 A using a synchrotron X-ray source...
  72. ncbi request reprint Final results of the ReoPro readministration registry
    Jean Pierre Dery
    Duke Clinical Research Institute, Durham, North Carolina, USA
    Am J Cardiol 93:979-84. 2004
    ..However, the rate of severe and profound TCP is increased relative to first-time administration, particularly when the time between treatments is <30 days or when HACA is present...
  73. ncbi request reprint Integrin alphaMbeta2 orchestrates and accelerates plasminogen activation and fibrinolysis by neutrophils
    Elzbieta Pluskota
    Joseph J Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Biol Chem 279:18063-72. 2004
    ..Thus, assembly of Plg and uPA on integrin alpha(M)beta(2) regulates Plm activity and, thereby, plays a crucial role in neutrophil-mediated thrombolysis...
  74. ncbi request reprint Mapping the interaction between high molecular mass kininogen and the urokinase plasminogen activator receptor
    Fakhri Mahdi
    Departments of Internal Medicine and Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Biol Chem 279:16621-8. 2004
    ..Therefore, HK interacts with suPAR at several sites. HK binds to uPAR as part of its interaction with its multiprotein receptor complex on HUVEC, and the biological functions that depend upon this binding are modulated by urokinase...
  75. ncbi request reprint Involvement of the urokinase kringle domain in lipopolysaccharide-induced acute lung injury
    Xue Qing Wang
    Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado, and Health Services Center, Denver, CO 80262, USA
    J Immunol 177:5550-7. 2006
    ..Blockade of the uPA KD may prevent the development or ameliorate the severity of acute lung injury induced through TLR4-dependent mechanisms, such as would occur in the setting of Gram-negative pulmonary or systemic infection...
  76. ncbi request reprint Pathogenesis of heparin-induced thrombocytopenia and thrombosis
    Gowthami Arepally
    Division of Hematology, Duke University Medical Center, Box 3486, Durham, NC 27710, USA
    Autoimmun Rev 1:125-32. 2002
    ..The recent development of a monoclonal anti-heparin/PF4 antibody and the establishment of a murine model of HIT/T may help to better define the pathogenesis and management of this common autoimmune disorder...
  77. ncbi request reprint Regulation of neovascularization by human neutrophil peptides (alpha-defensins): a link between inflammation and angiogenesis
    Triantafyllos Chavakis
    Institute for Biochemistry, Justus Liebig Universitat, Giessen, Germany
    FASEB J 18:1306-8. 2004
    ..These findings provide new insight into the role of inflammatory cells in angiogenesis and might provide a platform for developing a novel class of anti-angiogenesis drugs...
  78. ncbi request reprint Proteomic identification of lynchpin urokinase plasminogen activator receptor protein interactions associated with epithelial cancer malignancy
    Rohit G Saldanha
    Australian Proteome Analysis Facility Ltd and Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, 2109, NSW Australia
    J Proteome Res 6:1016-28. 2007
    ..Our findings support the notion that uPAR behaves as a lynchpin in promoting tumorigenesis by forming functionally active multiprotein complexes...
  79. pmc Inhibition of pathologic retinal neovascularization by alpha-defensins
    Matina Economopoulou
    Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Rm 4B17, 10 Center Dr, Bethesda, MD 20892, USA
    Blood 106:3831-8. 2005
    ..Together, these data show that alpha-defensins inhibit pathologic retinal neovascularization in vivo and may provide a clinically efficient strategy against proliferative retinopathies...

Research Grants11

  1. DEFENSIN AND THE PATHOGENESIS OF ATHEROSCLEROSIS
    Douglas Cines; Fiscal Year: 2002
    ..Finally, the interaction between endogenous defensin and endogenous Lp(a) will be examined in a novel transgenic mouse than overexpresses both human defensin and human Lp(a). ..
  2. STRUCTURE/FUNCTION ANALYSIS OF THE UROKINASE RECEPTOR
    Douglas Cines; Fiscal Year: 2002
    ..abstract_text> ..
  3. STRUCTURE/FUNCTION ANALYSIS OF THE UROKINASE RECEPTOR
    Douglas Cines; Fiscal Year: 2001
    ..abstract_text> ..
  4. DEFENSIN AND THE PATHOGENESIS OF ATHEROSCLEROSIS
    Douglas Cines; Fiscal Year: 2001
    ..Finally, the interaction between endogenous defensin and endogenous Lp(a) will be examined in a novel transgenic mouse than overexpresses both human defensin and human Lp(a). ..
  5. DEFENSIN AND THE PATHOGENESIS OF ATHEROSCLEROSIS
    Douglas Cines; Fiscal Year: 2000
    ..Finally, the interaction between endogenous defensin and endogenous Lp(a) will be examined in a novel transgenic mouse than overexpresses both human defensin and human Lp(a). ..
  6. STRUCTURE/FUNCTION ANALYSIS OF THE UROKINASE RECEPTOR
    Douglas Cines; Fiscal Year: 2000
    ..abstract_text> ..
  7. DEFENSIN AND THE PATHOGENESIS OF ATHEROSCLEROSIS
    Douglas Cines; Fiscal Year: 1999
    ..Finally, the interaction between endogenous defensin and endogenous Lp(a) will be examined in a novel transgenic mouse than overexpresses both human defensin and human Lp(a). ..
  8. STRUCTURE/FUNCTION ANALYSIS OF THE UROKINASE RECEPTOR
    Douglas Cines; Fiscal Year: 1999
    ..abstract_text> ..