John Griffin

Summary

Affiliation: The Scripps Research Institute
Country: USA

Publications

  1. ncbi request reprint The promise of protein C
    John H Griffin
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, MEM180, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Blood Cells Mol Dis 36:211-6. 2006
  2. pmc Protein C anticoagulant and cytoprotective pathways
    John H Griffin
    Department of Molecular and Experimental Medicine, MEM 180, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Int J Hematol 95:333-45. 2012
  3. pmc Protein S blocks the extrinsic apoptotic cascade in tissue plasminogen activator/N-methyl D-aspartate-treated neurons via Tyro3-Akt-FKHRL1 signaling pathway
    Huang Guo
    Center for Neurodegenerative and Vascular Brain Disorders, Department of Neurosurgery and Neurology, University of Rochester Medical Center, Rochester, NY 14642, USA
    Mol Neurodegener 6:13. 2011
  4. pmc Upregulated but insufficient generation of activated protein C is associated with development of multiorgan failure in severe acute pancreatitis
    Outi Lindstrom
    Second Department of Surgery, Helsinki University Central Hospital and University of Helsinki, Finland
    Crit Care 10:R16. 2006
  5. pmc High-density lipoprotein enhancement of anticoagulant activities of plasma protein S and activated protein C
    J H Griffin
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
    J Clin Invest 103:219-27. 1999
  6. ncbi request reprint Activated protein C
    J H Griffin
    Division of Translational Vascular Medicine, Department of Molecular and Experimental Medicine MEM 180, The Scripps Research Institute, La Jolla, CA, USA
    J Thromb Haemost 5:73-80. 2007
  7. ncbi request reprint Plasma lipoproteins, hemostasis and thrombosis
    J H Griffin
    Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA
    Thromb Haemost 86:386-94. 2001
  8. ncbi request reprint Causes of thrombophilia yet to be discovered: a personal view
    J H Griffin
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    Haemostasis 30:26-33. 2000
  9. ncbi request reprint Prothrombin residues 473-487 contribute to factor Va binding in the prothrombinase complex
    Subramanian Yegneswaran
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 279:49019-25. 2004
  10. pmc Prothrombin amino terminal region helps protect coagulation factor Va from proteolytic inactivation by activated protein C
    Subramanian Yegneswaran
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550, North Torrey Pines Road, MEM180, La Jolla, CA, 92037, USA
    Thromb Haemost 101:55-61. 2009

Research Grants

  1. STRUCTURE AND FUNCTION OF PROTEIN C
    John Griffin; Fiscal Year: 2009
  2. STRUCTURE AND FUNCTION OF PROTEIN C
    John H Griffin; Fiscal Year: 2010
  3. PROTEINS OF COAGULATION PATHWAYS
    John H Griffin; Fiscal Year: 2010
  4. STRUCTURE AND FUNCTION OF PROTEIN C
    John Griffin; Fiscal Year: 2007
  5. PROTEINS OF COAGULATION PATHWAYS
    John Griffin; Fiscal Year: 2007
  6. Novel targets and agents to treat thrombotic disorders
    John Griffin; Fiscal Year: 2004
  7. PROTEINS OF COAGULATION PATHWAYS
    John Griffin; Fiscal Year: 2003
  8. PROTEINS OF COAGULATION PATHWAYS
    John Griffin; Fiscal Year: 1993
  9. PROTEINS OF COAGULATION PATHWAYS
    John Griffin; Fiscal Year: 1999
  10. STRUCTURE AND FUNCTION OF PROTEIN C
    John H Griffin; Fiscal Year: 2011

Collaborators

Detail Information

Publications69

  1. ncbi request reprint The promise of protein C
    John H Griffin
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, MEM180, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Blood Cells Mol Dis 36:211-6. 2006
    ..This review summarizes data from clinical observations, from in vitro studies, and from animal models of focal ischemic injury that provide a compelling rationale for clinical trials of APC for ischemic stroke...
  2. pmc Protein C anticoagulant and cytoprotective pathways
    John H Griffin
    Department of Molecular and Experimental Medicine, MEM 180, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Int J Hematol 95:333-45. 2012
    ..This review summarizes the molecules that are central to the protein C pathways, the relationship of pathway deficiencies to venous thrombosis risk, and mechanisms for the beneficial effects of APC...
  3. pmc Protein S blocks the extrinsic apoptotic cascade in tissue plasminogen activator/N-methyl D-aspartate-treated neurons via Tyro3-Akt-FKHRL1 signaling pathway
    Huang Guo
    Center for Neurodegenerative and Vascular Brain Disorders, Department of Neurosurgery and Neurology, University of Rochester Medical Center, Rochester, NY 14642, USA
    Mol Neurodegener 6:13. 2011
    ..abstract:..
  4. pmc Upregulated but insufficient generation of activated protein C is associated with development of multiorgan failure in severe acute pancreatitis
    Outi Lindstrom
    Second Department of Surgery, Helsinki University Central Hospital and University of Helsinki, Finland
    Crit Care 10:R16. 2006
    ..We therefore evaluated circulating levels of PC and activated protein C (APC), evaluated monocyte deactivation in AP patients, and determined the relationship of these parameters to MOF...
  5. pmc High-density lipoprotein enhancement of anticoagulant activities of plasma protein S and activated protein C
    J H Griffin
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
    J Clin Invest 103:219-27. 1999
    ..Because HDL enhances the anticoagulant protein C pathway in vitro, we speculate that HDL may help downregulate thrombin generation in vivo and that this anticoagulant action is one of HDL's beneficial activities...
  6. ncbi request reprint Activated protein C
    J H Griffin
    Division of Translational Vascular Medicine, Department of Molecular and Experimental Medicine MEM 180, The Scripps Research Institute, La Jolla, CA, USA
    J Thromb Haemost 5:73-80. 2007
    ....
  7. ncbi request reprint Plasma lipoproteins, hemostasis and thrombosis
    J H Griffin
    Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA
    Thromb Haemost 86:386-94. 2001
    ..We hypothesize that procoagulant and anticoagulant lipids and lipoproteins in plasma may contribute to a Yin-Yang balance that helps influence the up-regulation and down-regulation of thrombin generation...
  8. ncbi request reprint Causes of thrombophilia yet to be discovered: a personal view
    J H Griffin
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    Haemostasis 30:26-33. 2000
    ..The Human Genome Project will soon accelerate discovery of new SNPs that are risk factors for venous thrombosis...
  9. ncbi request reprint Prothrombin residues 473-487 contribute to factor Va binding in the prothrombinase complex
    Subramanian Yegneswaran
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 279:49019-25. 2004
    ..These functional and spectroscopic data suggest that fII residues 473-487 provide fVa-binding sites and mediate interactions between fVa and fII in the prothrombinase complex...
  10. pmc Prothrombin amino terminal region helps protect coagulation factor Va from proteolytic inactivation by activated protein C
    Subramanian Yegneswaran
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550, North Torrey Pines Road, MEM180, La Jolla, CA, 92037, USA
    Thromb Haemost 101:55-61. 2009
    ..Only following FII activation and dissociation of the FII Gla domain fragments from the FII-ase complex, can APC inactivate FVa and down-regulate thrombin generation...
  11. ncbi request reprint Factor Va residues 311-325 represent an activated protein C binding region
    Subramanian Yegneswaran
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 282:28353-61. 2007
    ..These data suggest that peptide VP311-325 represents both an APC and fXa binding region in fVa...
  12. ncbi request reprint Identification of distinct sequences in human blood coagulation factor Xa and prothrombin essential for substrate and cofactor recognition in the prothrombinase complex
    Subramanian Yegneswaran
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 278:33312-8. 2003
    ..These data suggest that residues 404-418 in fXa provide fVa binding sites, whereas residues 557-571 in fII and 415-429 in fXa mediate interactions between fXa and fII in the prothrombinase complex...
  13. ncbi request reprint Recombinant murine-activated protein C is neuroprotective in a murine ischemic stroke model
    Jose A Fernandez
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    Blood Cells Mol Dis 30:271-6. 2003
    ..The results imply that murine APC is notably superior to human APC for studies of murine disease models, including thrombosis and ischemic brain injury...
  14. pmc Interdomain engineered disulfide bond permitting elucidation of mechanisms of inactivation of coagulation factor Va by activated protein C
    Andrew J Gale
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
    Protein Sci 11:2091-101. 2002
    ..Nonetheless, for FVa Leiden (Gln506-FVa) inactivation by APC, A2 domain dissociation may become mechanistically important, depending on the ambient FXa concentration...
  15. pmc Species-specific anticoagulant and mitogenic activities of murine protein S
    Jose A Fernandez
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    Haematologica 94:1721-31. 2009
    ..In preclinical studies using models of murine injury (e.g., sepsis and ischemic stroke), murine protein S may be required because of restrictive species specificity...
  16. ncbi request reprint Characterization of a thrombomodulin binding site on protein C and its comparison to an activated protein C binding site for factor Va
    Andrew J Gale
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
    Proteins 54:433-41. 2004
    ..Thus, the extensive basic surface of protein C and activated protein C provides distinctly different, though significantly overlapping, binding sites for recognition by thrombin-thrombomodulin and factor Va...
  17. ncbi request reprint Factor Va increases the affinity of factor Xa for prothrombin: a binding study using a novel photoactivable thiol-specific fluorescent probe
    Subramanian Yegneswaran
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    Chem Biol 9:485-94. 2002
    ..These data demonstrate that LWB can successfully function both as a spectroscopic probe and as a photocrosslinking reagent for studying protein-protein interactions...
  18. ncbi request reprint Sphingolipids as bioactive regulators of thrombin generation
    Hiroshi Deguchi
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, MEM 180, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    J Biol Chem 279:12036-42. 2004
    ..Thus, certain sphingolipids may be bioactive lipid mediators of thrombin generation such that certain sphingolipid metabolites may modulate proteases that affect cell growth and death, blood coagulation, and inflammation...
  19. pmc The thrombin-sensitive region of protein S mediates phospholipid-dependent interaction with factor Xa
    Subramanian Yegneswaran
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 283:33046-52. 2008
    ..In controls, the TSR domain did not alter the anisotropy of DEGR-fIXa(i) and DEGR-fVIIa(i), respectively. These data demonstrate that membrane-bound fXa binding to protein S involves the TSR of protein S...
  20. ncbi request reprint Glucosylceramide, a neutral glycosphingolipid anticoagulant cofactor, enhances the interaction of human- and bovine-activated protein C with negatively charged phospholipid vesicles
    Subramanian Yegneswaran
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 278:14614-21. 2003
    ....
  21. ncbi request reprint Plasma cholesteryl ester transfer protein and blood coagulability
    Hiroshi Deguchi
    Dept of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA
    Thromb Haemost 98:1160-4. 2007
    ..Thus, our data highlight a previously unknown positive relationship between CETP plasma levels and blood coagulability that might relate to risks for thrombotic events...
  22. ncbi request reprint Characterization of a factor Xa binding site on factor Va near the Arg-506 activated protein C cleavage site
    Andrew J Gale
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Biol Chem 282:21848-55. 2007
    ....
  23. ncbi request reprint Protein C anticoagulant activity in relation to anti-inflammatory and anti-apoptotic activities
    Laurent O Mosnier
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    Front Biosci 11:2381-99. 2006
    ....
  24. ncbi request reprint Activated protein C in the cardioplegic solution on a porcine model of coronary ischemia-reperfusion has deleterious hemodynamic effects
    Jose A Fernandez
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
    Cardiovasc Drugs Ther 20:113-21. 2006
    ..Activated protein C (APC) exhibits anticoagulant and anti-inflammatory properties in models of reperfusion injury. We hypothesized that APC could be cardioprotective after ischemia and cardiopulmonary bypass (CPB)...
  25. ncbi request reprint A novel ELISA for mouse activated protein C in plasma
    Jose A Fernandez
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, United States
    J Immunol Methods 314:174-81. 2006
    ..The amount of complex APC:PCI is detected with an anti-human PCI monoclonal antibody. The assay shows improved sensitivity versus enzyme immunocapture assays commonly used to detect human APC and considerably reduces the processing time...
  26. ncbi request reprint The cytoprotective protein C pathway
    Laurent O Mosnier
    Department of Molecular and Experimental Medicine MEM 180, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, USA
    Blood 109:3161-72. 2007
    ....
  27. ncbi request reprint Activated protein C mutant with minimal anticoagulant activity, normal cytoprotective activity, and preservation of thrombin activable fibrinolysis inhibitor-dependent cytoprotective functions
    Laurent O Mosnier
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    J Biol Chem 282:33022-33. 2007
    ....
  28. pmc Endogenous EPCR/aPC-PAR1 signaling prevents inflammation-induced vascular leakage and lethality
    Frank Niessen
    Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA
    Blood 113:2859-66. 2009
    ..Thus, the activating proteases and selectivity in coupling to S1P receptor subtypes determine vascular PAR1 signaling specificity in systemic inflammatory response syndromes in vivo...
  29. pmc Plasma protein S contains zinc essential for efficient activated protein C-independent anticoagulant activity and binding to factor Xa, but not for efficient binding to tissue factor pathway inhibitor
    Mary J Heeb
    Department of Molecular and Experimental Medicine, MEM276, Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
    FASEB J 23:2244-53. 2009
    ..Thus, Zn(2+) is required for PS-direct and efficient FXa binding and may play a role in stabilizing PS conformation...
  30. pmc Protection of vascular barrier integrity by activated protein C in murine models depends on protease-activated receptor-1
    Reto A Schuepbach
    Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA
    Thromb Haemost 101:724-33. 2009
    ..Our data in vitro and in vivo support the paradigm that PAR1 contributes to protective effects of APC on vascular barrier integrity in sepsis...
  31. ncbi request reprint Activated protein C-dependent and -independent anticoagulant activities of protein S have different structural requirements
    Mary J Heeb
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
    Blood Cells Mol Dis 29:190-9. 2002
    ..Thus, the APC-cofactor activity protein S is significantly more sensitive to structural changes in the TSR than is the APC-independent activity of protein S...
  32. ncbi request reprint Molecular characterization of an extended binding site for coagulation factor Va in the positive exosite of activated protein C
    Andrew J Gale
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 277:28836-40. 2002
    ..In conjunction with previously published work, these results define an extensive FVa binding site in the positive exosite of APC that is primarily involved in binding and cleaving at Arg(506) on FVa...
  33. ncbi request reprint Low protein Z levels and risk of ischemic stroke: differences by diabetic status and gender
    Mary J Heeb
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    Blood Cells Mol Dis 29:139-44. 2002
    ..015). Protein Z is suggested to be a physiologic downregulator of blood coagulation and low protein Z levels are associated with increased risk of ischemic stroke, particularly in males and in the absence of diabetes...
  34. ncbi request reprint Protein C pathway impairment in nonsymptomatic cigarette smokers
    Jose A Fernandez
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road MEM 180, La Jolla, CA 92037, USA
    Blood Cells Mol Dis 29:73-82. 2002
    ..Cigarette smoke dose-dependent hypercoagulability due to acquired activated protein C deficiency could contribute to the increased risk of thrombosis in smokers...
  35. ncbi request reprint Activated protein C variants with normal cytoprotective but reduced anticoagulant activity
    Laurent O Mosnier
    Department of Molecular and Experimental Medicine MEM 180, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Blood 104:1740-4. 2004
    ..We suggest that therapeutic use of such APC variants may reduce serious bleeding risks while providing the beneficial effects of APC acting directly on cells...
  36. ncbi request reprint Neutral glycosphingolipid-dependent inactivation of coagulation factor Va by activated protein C and protein S
    Hiroshi Deguchi
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 277:8861-5. 2002
    ..We speculate that under some circumstances certain neutral glycosphingolipids either in lipoprotein particles or in cell membranes may help form antithrombotic microdomains that might enhance down-regulation of thrombin by APC in vivo...
  37. ncbi request reprint Activated protein C: potential therapy for severe sepsis, thrombosis, and stroke
    John H Griffin
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 N Torrey Pines Road, MEM 180, La Jolla, CA 92037, USA
    Semin Hematol 39:197-205. 2002
    ..Because of its multiple activities, APC has a potential role in the treatment of complex and challenging medical disorders, including thrombosis and stroke...
  38. ncbi request reprint Protective signaling by activated protein C is mechanistically linked to protein C activation on endothelial cells
    Clemens Feistritzer
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 281:20077-84. 2006
    ..WE may have powerful protective effects in systemic inflammation through signaling by the endogenously generated APC...
  39. ncbi request reprint Activated protein C and ischemic stroke
    John H Griffin
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA
    Crit Care Med 32:S247-53. 2004
    ..To summarize clinical observations, animal model experimentation, and in vitro studies that advance knowledge of the protein C system, including activated protein C (APC), in the setting of ischemic stroke...
  40. pmc Hyperantithrombotic, noncytoprotective Glu149Ala-activated protein C mutant
    Laurent 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...
  41. pmc Activated protein C ligation of ApoER2 (LRP8) causes Dab1-dependent signaling in U937 cells
    Xia V Yang
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 106:274-9. 2009
    ..Thus, we propose that ligation of ApoER2 by APC signals via Dab1 phosphorylation and subsequent activation of PI3K and Akt and inactivation of GSK3beta, thereby contributing to APC's beneficial effects on cells...
  42. pmc Inhibition of staurosporine-induced apoptosis of endothelial cells by activated protein C requires protease-activated receptor-1 and endothelial cell protein C receptor
    Laurent O Mosnier
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Biochem J 373:65-70. 2003
    ..Consistent with this implication, both protease-activated receptor-1 (PAR-1) and endothelial cell protein C receptor (EPCR) were required for the anti-apoptotic effects of activated protein C...
  43. ncbi request reprint High-density lipoprotein deficiency and dyslipoproteinemia associated with venous thrombosis in men
    Hiroshi Deguchi
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Rd, La Jolla, CA 92037, USA
    Circulation 112:893-9. 2005
    ..Although dyslipoproteinemia is associated with arterial atherothrombosis, little is known about plasma lipoproteins in venous thrombosis patients...
  44. ncbi request reprint Protein S confers neuronal protection during ischemic/hypoxic injury in mice
    Dong Liu
    Frank P Smith Neurosurgical Research Laboratory, Division of Neurovascular Biology, University of Rochester Medical Center, 601 Elmwood Ave, Box 645, Rochester, NY 14642, USA
    Circulation 107:1791-6. 2003
    ..Protein S is an antithrombotic factor that also exhibits mitogenic activity. Thus, we hypothesized that protein S may control cerebrovascular thrombosis in stroke and protect brain tissue from ischemic injury...
  45. pmc Endotoxemia and sepsis mortality reduction by non-anticoagulant activated protein C
    Edward J Kerschen
    Blood Research Institute, Milwaukee, WI 53226, USA
    J Exp Med 204:2439-48. 2007
    ....
  46. ncbi request reprint Oral anticoagulation reduces activated protein C less than protein C and other vitamin K-dependent clotting factors
    Marleen J A Simmelink
    Thrombosis and Haemostasis Laboratory, Department of Haematology, and Department of Rheumatology and Clinical Immunology, University Medical Center, Utrecht, The Netherlands
    Blood 100:4232-3. 2002
    ....
  47. doi request reprint Failure to validate association of gene polymorphisms in EPCR, PAR-1, FSAP and protein S Tokushima with venous thromboembolism among Californians of European ancestry
    Natalie M Pecheniuk
    Thromb Haemost 99:453-5. 2008
  48. ncbi request reprint Effect of hyperhomocysteinemia on protein C activation and activity
    Steven R Lentz
    Department of Internal Medicine, Veterans Affairs Medical Center, C303 GH, University of Iowa, Iowa City, IA 52242, USA
    Blood 100:2108-12. 2002
    ..Our findings indicate that activation of protein C by thrombin and inactivation of plasma FVa by APC are not impaired during moderate hyperhomocysteinemia in vivo...
  49. ncbi request reprint Activated protein C reduces graft neutrophil activation in clinical renal transplantation
    Arto J Turunen
    Helsinki University Hospital, Helsinki, Finland
    Am J Transplant 5:2204-12. 2005
    ..8, p=0.001), and with both warm (r=0.6, p=0.01) and cold ischemia time (r=0.6, p=0.02) and donor age (r=0.6, p=0.01). These findings suggest that APC has an anti-inflammatory role in I/R injury in clinical renal transplantation...
  50. ncbi request reprint Anticoagulant responses to thrombin are enhanced during regression of atherosclerosis in monkeys
    Steven R Lentz
    Veterans Affairs Medical Center, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA
    Circulation 106:842-6. 2002
    ..We tested the hypothesis that anticoagulant responses to thrombin increase toward normal during regression of atherosclerosis...
  51. ncbi request reprint Conversion of a plant oxidosqualene-cycloartenol synthase to an oxidosqualene-lanosterol cyclase by random mutagenesis
    Tung Kung Wu
    Department of Biological Science and Technology, National Chiao Tung University, Hsin Chu, 300, Taiwan, Republic of China
    Biochemistry 41:8238-44. 2002
    ..Sequence and structural homology modeling of CAS indicate that the observed product specificity-altering mutations occur both within (Tyr410Cys, Ile481Thr, and Tyr532His) and outside of (Ala469Val and His477Tyr) the cyclase active site...
  52. ncbi request reprint Activated protein C preserves functional islet mass after intraportal transplantation: a novel link between endothelial cell activation, thrombosis, inflammation, and islet cell death
    Juan L Contreras
    Division of Transplantation and Transplant Center, University of Alabama at Birmingham, USA
    Diabetes 53:2804-14. 2004
    ..This study demonstrates multiple remarkable beneficial effects of mAPC for PIT and suggests that APC therapy may enhance the therapeutic efficacy of PIT in diabetic patients...
  53. ncbi request reprint Low levels of activated protein C in patients with systemic lupus erythematosus do not relate to lupus anticoagulants but to low levels of factor II
    Marleen J A Simmelink
    Thrombosis and Haemostasis Laboratory, Department of Haematology, University Medical Centre Utrecht, Heidelberglaan 100, 3584 GA Utrecht, The Netherlands
    Br J Haematol 117:676-84. 2002
    ..As FII levels, and not protein C levels, were decreased in SLE patients and correlated with APC levels, we conclude that the decreased FII levels are responsible for the low levels of APC...
  54. ncbi request reprint Activation of protein C and hemodynamic recovery after coronary artery bypass surgery
    Peter Raivio
    Department of Cardiothoracic Surgery, Helsinki University Central Hospital, Helsinki, Finland
    J Thorac Cardiovasc Surg 133:44-51. 2007
    ....
  55. ncbi request reprint Functional recovery after embolic stroke in rodents by activated protein C
    Berislav V Zlokovic
    Department of Neurosurgery and Division of Neurovascular Biology, Frank P Smith Laboratory for Neuroscience and Neurosurgical Research, University of Rochester Medical Center, Rochester, NY 14642, USA
    Ann Neurol 58:474-7. 2005
    ..In contrast, tissue plasminogen activator alone was not protective. Thus, activated protein C may be useful as a new stand-alone therapy for clinical stroke and to extend the time window of thrombolytic therapy...
  56. ncbi request reprint Soluble thrombomodulin is antithrombotic in the presence of neutralising antibodies to protein C and reduces circulating activated protein C levels in primates
    Kenichi A Tanaka
    Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, USA
    Br J Haematol 132:197-203. 2006
    ..Direct inhibition of thrombin's prothrombotic activity upon complex formation with rhsTM might explain the molecular mechanism of the observed antithrombotic effect...
  57. pmc Relative antithrombotic and antihemostatic effects of protein C activator versus low-molecular-weight heparin in primates
    Andras Gruber
    Department of Biomedical Engineering, Oregon Health and Science University, 3303 SW Bond Avenue, Portland, OR 97239, USA
    Blood 109:3733-40. 2007
    ..Our data suggest that limited pharmacological protein C activation might exhibit considerable thrombosis specificity...
  58. ncbi request reprint Graft protein C entrapment is associated with reduced phagocyte activation during reperfusion in human liver transplantation
    Minna Ilmakunnas
    Transplantation and Liver Surgery Clinic, Fourth Department of Surgery, Helsinki University Central Hospital, Finland
    Crit Care Med 34:426-32. 2006
    ..To explore the potential anti-inflammatory role of protein C pathway in ischemia-reperfusion injury during liver transplantation...
  59. ncbi request reprint Activated protein C blocks p53-mediated apoptosis in ischemic human brain endothelium and is neuroprotective
    Tong Cheng
    Frank P Smith Neurosurgical Research Laboratory, Department of Neurosurgery and Center for Aging and Developmental Biology, Division of Neurovascular Biology, University of Rochester Medical Center, Rochester, New York, USA
    Nat Med 9:338-42. 2003
    ..9). Moreover, the in vivo neuroprotective effects of low-dose mouse APC seemed to be independent of its anti-coagulant activity. Thus, APC protects the brain from ischemic injury by acting directly on brain cells...
  60. ncbi request reprint Tissue plasminogen activator neurovascular toxicity is controlled by activated protein C
    Dong Liu
    Frank P Smith Laboratory for Neuroscience and Neurosurgical Research, Department of Neurosurgery and Division of Neurovascular Biology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 645, Rochester, New York 14642, USA
    Nat Med 10:1379-83. 2004
    ..APC blocks tPA's neurovascular toxicity and may add substantially to the effectiveness of tPA therapy for stroke...
  61. ncbi request reprint Platelet factor 4 enhances generation of activated protein C in vitro and in vivo
    Arne Slungaard
    Department of Medicine, Section of Hematology, Oncology and Transplantation, University of Minnesota, Mayo Mail Code 480, 420 Delaware St SE, Minneapolis, MN 55455, USA
    Blood 102:146-51. 2003
    ..These findings suggest that PF4 may play a previously unsuspected physiologic role in enhancing APC generation...
  62. ncbi request reprint Activation of protein C during reperfusion in clinical liver transplantation
    Minna Ilmakunnas
    Transplantation and Liver Surgery Clinic, Fourth Department of Surgery, University of Helsinki, Finland
    Transplantation 75:467-72. 2003
    ..We studied the kinetics and magnitude of protein C activation in clinical liver transplantation and the interaction of this activation with neutrophil and monocyte activation...
  63. ncbi request reprint Activated protein C prevents neuronal apoptosis via protease activated receptors 1 and 3
    Huang Guo
    Socratech Laboratories, Rochester, NY 14620, USA
    Neuron 41:563-72. 2004
    ..Thus, PAR1 and PAR3 mediate anti-apoptotic signaling by APC in neurons, which may suggest novel treatments for neurodegenerative disorders...
  64. ncbi request reprint Multivalent drug design. Synthesis and in vitro analysis of an array of vancomycin dimers
    John H Griffin
    Contribution from Theravance, Inc, 901 Gateway Boulevard, South San Francisco, California 94080, USA
    J Am Chem Soc 125:6517-31. 2003
    ..aureus (MRSA) and glycopeptide-intermediate susceptible S. aureus (GISA). In interpreting the results, we have considered the potential roles of multivalency and of other phenomena...
  65. ncbi request reprint Endothelial and antithrombotic actions of HDL
    Chieko Mineo
    Division of Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390 9063, USA
    Circ Res 98:1352-64. 2006
    ..With further investigation and resulting greater depth of understanding, these mechanisms may be harnessed to provide new prophylactic and therapeutic strategies to combat atherosclerosis and thrombotic disorders...
  66. ncbi request reprint Activated protein C alters cytosolic calcium flux in human brain endothelium via binding to endothelial protein C receptor and activation of protease activated receptor-1
    Eszter Domotor
    Frank P Smith Neurological Research Laboratory, Department of Neurosurgery and Division of Neurovascular Biology, University of Rochester Medical Center, NY 14642, USA
    Blood 101:4797-801. 2003
    ..These data suggest that APC regulates [Ca2+]i in human brain endothelium and in HUVECs by binding to EPCR and signaling via PAR-1...
  67. ncbi request reprint Activated protein C inhibits tissue plasminogen activator-induced brain hemorrhage
    Tong Cheng
    Frank P Smith Laboratory for Neuroscience and Neurosurgical Research, Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York 14642, USA
    Nat Med 12:1278-85. 2006
    ..The present findings suggest that APC may improve thrombolytic therapy for stroke, in part, by reducing tPA-mediated hemorrhage...
  68. ncbi request reprint High-density lipoprotein and the risk of recurrent venous thromboembolism
    Sabine Eichinger
    Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
    Circulation 115:1609-14. 2007
    ..High-density lipoprotein (HDL) protects against arterial atherothrombosis, but it is unknown whether it protects against recurrent venous thromboembolism...
  69. ncbi request reprint Coagulation pathways in atherothrombosis
    Alexey V Khrenov
    Department of Biochemistry, Holland Laboratory, American Red Cross, Rockville, Maryland 20855, USA
    Trends Cardiovasc Med 12:317-24. 2002
    ..The present review discusses contribution of the extrinsic and intrinsic pathways of blood coagulation in thrombogenicity of atherosclerotic plaque and factors determining the overall procoagulant/anticoagulant balance...

Research Grants27

  1. STRUCTURE AND FUNCTION OF PROTEIN C
    John Griffin; Fiscal Year: 2009
    ..These studies will improve our ability to understand, diagnose and treat thrombotic diseases. ..
  2. STRUCTURE AND FUNCTION OF PROTEIN C
    John H Griffin; Fiscal Year: 2010
    ..The findings may well be translatable into future clinical advances. ..
  3. PROTEINS OF COAGULATION PATHWAYS
    John H Griffin; Fiscal Year: 2010
    ..This project will increase insights into the pathophysiology of thrombosis and may improve diagnosis and treatment of thrombosis. ..
  4. STRUCTURE AND FUNCTION OF PROTEIN C
    John Griffin; Fiscal Year: 2007
    ..These studies will improve our ability to understand, diagnose and treat thrombotic diseases. ..
  5. PROTEINS OF COAGULATION PATHWAYS
    John Griffin; Fiscal Year: 2007
    ..The proposed studies will increase our insights into the pathophysiology of thrombosis and are likely to improve diagnosis and treatment of thrombosis. ..
  6. Novel targets and agents to treat thrombotic disorders
    John Griffin; Fiscal Year: 2004
    ..abstract_text> ..
  7. PROTEINS OF COAGULATION PATHWAYS
    John Griffin; Fiscal Year: 2003
    ..The proposed studies of HDL, GlcCer, protein S and factor Va will increase our insights into the regulation of blood coagulation and thrombosis. ..
  8. PROTEINS OF COAGULATION PATHWAYS
    John Griffin; Fiscal Year: 1993
    ..These studies will provide new knowledge about natural anticoagulant mechanisms and will be potentially useful for developing new approaches to regulate thrombosis...
  9. PROTEINS OF COAGULATION PATHWAYS
    John Griffin; Fiscal Year: 1999
    ..The proposed structure-function studies of protein S and of factor Va will contribute to our understanding of the pathophysiology of thrombosis and thereby eventually to the improved treatment of patients with thrombosis. ..
  10. STRUCTURE AND FUNCTION OF PROTEIN C
    John H Griffin; Fiscal Year: 2011
    ..The findings may well be translatable into future clinical advances. ..