Research Topics
| NIGEL contact MACKMANSummaryAffiliation: University of North Carolina Country: USA Publications
Research Grants
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Detail Information
Publications
Role of the extrinsic pathway of blood coagulation in hemostasis and thrombosisNigel Mackman
Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, Mail Code SP30 3040, La Jolla, CA 92037, USA
Arterioscler Thromb Vasc Biol 27:1687-93. 2007..Understanding how the extrinsic pathway of blood coagulation contributes to hemostasis and thrombosis may lead to the development of safe and effective hemostatic agents and antithrombotic drugs...
Triggers, targets and treatments for thrombosisNigel Mackman
Division of Hematology Oncology, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA
Nature 451:914-8. 2008..The pathogenic changes that occur in the blood vessel wall and in the blood itself resulting in thrombosis are not fully understood. Understanding these processes is crucial for developing safer and more effective antithrombotic drugs...- New insights into the mechanisms of venous thrombosisNigel Mackman
Division of Hematology Oncology, Department of Medicine, UNC McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
J Clin Invest 122:2331-6. 2012..Subsequent activation of the leukocytes induces expression of the potent procoagulant protein tissue factor that triggers thrombosis. Understanding the mechanisms of venous thrombosis may lead to the development of new treatments... - The many faces of tissue factorN Mackman
Division of Hematology and Oncology, Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
J Thromb Haemost 7:136-9. 2009..In endotoxemia and sepsis, TF-dependent thrombin generation and activation of PAR1 on dendritic cells enhance inflammation. Finally, the TF:FVIIa complex contributes to tumor growth by activating PAR2... 
Tissue factor and its measurement in whole blood, plasma, and microparticlesNigel S Key
Division of Hematology Oncology, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA
Semin Thromb Hemost 36:865-75. 2010..We comment on some of the crucial preanalytical and analytical variables that influence the results and their interpretation...- Venous thromboembolism: a need for more public awareness and research into mechanismsStephan Moll
Division of Hematology/Oncology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7035, USA
Arterioscler Thromb Vasc Biol 28:367-9. 2008 - Tissue factor and thrombosis: The clot starts hereA Phillip Owens
Division of Hematology Oncology, Department of Medicine, University of North Carolina at Chapel Hill, USA
Thromb Haemost 104:432-9. 2010..Understanding the role of TF in thrombosis may permit the development of new antithrombotic drugs. This review will focus on the role of TF in in vivo models of thrombosis... - Role of tissue factor in cancerRaj S Kasthuri
Division of Hematology and Oncology, Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
J Clin Oncol 27:4834-8. 2009..Nevertheless, additional studies are needed to determine if this strategy can be successfully translated to the treatment of cancer patients... - Microparticles in hemostasis and thrombosisA Phillip Owens
Division of Hematology Oncology, Department of Medicine, McAllister Heart Institute, University of North Carolina at Chapel Hill, North Carolina, USA
Circ Res 108:1284-97. 2011..This review will summarize our current knowledge of the role of procoagulant MPs in hemostasis and thrombosis... - Microparticles and cancerChirag Amin
Department of Medicine and Program in Hemostasis and Thrombosis, Carolina Cardiovascular Biology Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA
Pathophysiol Haemost Thromb 36:177-83. 2008.... - The role of tissue factor and factor VIIa in hemostasisNigel Mackman
Department of Medicine, Division of Hematology Oncology, University of North Carolina at Chapel Hill, NC 27599 7035, USA
Anesth Analg 108:1447-52. 2009..However, the mechanism by which recombinant FVIIa restores hemostasis has not been clearly defined. In conclusion, the TF:FVIIa complex is essential for hemostasis and recombinant FVIIa is an effective hemostatic drug... - Potent inhibition of thrombin with a monoclonal antibody against tissue factor (Sunol-cH36): results of the PROXIMATE-TIMI 27 trialDavid A Morrow
TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women s Hospital, 75 Francis Street, Boston, MA 02115, USA
Eur Heart J 26:682-8. 2005..Sunol-cH36, a chimaeric monoclonal antibody to TF, blocks binding of factor X to the TF:VIIa complex. This report describes the first completed trial of Sunol-cH36 in humans... - Role of tissue factor in a mouse model of thrombotic microangiopathy induced by antiphospholipid antibodiesSurya V Seshan
Department of Pathology, Department of Medicine, Weill Cornell Medical College, New York, NY, USA
Blood 114:1675-83. 2009..Treatment with pravastatin, which down-regulates glomerular TF synthesis, prevents aPL-induced TMA in this mouse model, thus emphasizing that targeting TF might be a good therapeutic intervention in patients with TMA... - Role of the coagulation system in acetaminophen-induced hepatotoxicity in micePatricia E Ganey
Department of Pharmacology and Toxicology, National Food Safety and Toxicology Center, Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824, USA
Hepatology 46:1177-86. 2007..CONCLUSION: Activation of the coagulation system and PAR-1 signaling contribute significantly to APAP-induced liver injury... - A non-anticoagulant synthetic pentasaccharide reduces inflammation in a murine model of kidney ischemia-reperfusion injuryRolf Dario Frank
Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Thromb Haemost 96:802-6. 2006..These findings indicate that the anti-inflammatory activity of fondaparinux can be dissociated from its anticoagulant activity and that NAC-pentasaccharide is protective in kidney I/R injury... - Oncogenes, trousseau syndrome, and cancer-related changes in the coagulome of mice and humansJanusz Rak
Montreal Children s Hospital Research Institute, McGill University, Montreal, Quebec, Canada
Cancer Res 66:10643-6. 2006.... - Tissue factor deficiency and PAR-1 deficiency are protective against renal ischemia reperfusion injuryJacob Sevastos
Prince of Wales Clinical School, University of New South Wales, Sydney, and Prince of Wales Hospital, Barker St, Randwick, NSW 2031, Australia
Blood 109:577-83. 2007..These experiments indicate that increased TF activity after renal IR leads to increased CXC chemokine expression and subsequent neutrophil-mediated injury predominantly by thrombin-dependent PAR-1 signaling... - Role of tissue factor in hemostasis, thrombosis, and vascular developmentNigel Mackman
The Scripps Research Institute, Department of Immunology, 10550 North Torrey Pines Road, La Jolla, Calif 92037, USA
Arterioscler Thromb Vasc Biol 24:1015-22. 2004..This review focuses on the roles of TF in hemostasis, thrombosis, and vascular development... - Tissue factor, coagulation proteases, and protease-activated receptors in endotoxemia and sepsisRafal Pawlinski
Departments of Immunology and Cell Biology, The Scripps Research Institute, La Jolla, CA, USA
Crit Care Med 32:S293-7. 2004..Taken together, our results suggest that activation of multiple PARs by coagulation proteases enhances inflammation during endotoxemia... - Hematopoietic cell-derived microparticle tissue factor contributes to fibrin formation during thrombus propagationJanet Chou
Center for Hemostasis and Thrombosis Research, Vascular Biology Center, 330 Brookline Ave, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
Blood 104:3190-7. 2004..This demonstrates that blood-borne TF associated with hematopoietic cell-derived microparticles contributes to thrombus propagation... - Macrovascular thrombosis is driven by tissue factor derived primarily from the blood vessel wallSharlene M Day
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Blood 105:192-8. 2005..Therefore, our results suggest that thrombus formation in the arterial and venous macrovasculature is driven primarily by TF derived from the blood vessel wall as opposed to leukocytes... - Mouse models in haemostasis and thrombosisNigel Mackman
Thromb Haemost 92:440-3. 2004 - Role of tissue factor in haemostasis, thrombosis, angiogenesis and inflammation: lessons from low tissue factor miceRafal Pawlinski
The Scripps Research Institute, 10550 North Torrey Pines Road, CVN-18, La Jolla, CA 92017, USA
Thromb Haemost 92:444-50. 2004..Low TF mice are also a useful tool to study the role of TF and the coagulation cascade in other processes, such as thrombosis, inflammation and angiogenesis... - Regulation of tissue factor--mediated initiation of the coagulation cascade by cell surface grp78Gourab Bhattacharjee
Department of Immunology, The Scripps Research Institute, SP258, La Jolla, CA 92037, USA
Arterioscler Thromb Vasc Biol 25:1737-43. 2005..To test the hypothesis that Grp78 negatively regulates cell surface tissue factor (TF) procoagulant activity and whether this is mediated by physical interaction... - Tissue-specific hemostasis in miceNigel Mackman
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA
Arterioscler Thromb Vasc Biol 25:2273-81. 2005..These observations, together with the phenotypes of mice that have defects in the procoagulant, anticoagulant, and fibrinolytic pathways, indicate that hemostasis is regulated in a tissue-specific manner... - Postprandial elevation of tissue factor antigen in the blood of healthy adultsDeborah D Motton
Division of Endocrinology, Clinical Nutrition and Vascular Medicine, Department of Internal Medicine, Suite 5303, Genomics and Biomedical Sciences Facility, University of California, Davis, California 95616, USA
Thromb Haemost 94:504-9. 2005..These results demonstrate increased tissue factor levels in individuals who consumed a moderate fat diet. This suggests that the typical western diet may play a larger role in cardiovascular disease than merely altering lipid profiles... - Role of tissue factor in hemostasis and thrombosisNigel Mackman
Departments of Immunology and Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, CVN 18, La Jolla, CA 92037, USA
Blood Cells Mol Dis 36:104-7. 2006..Inhibition of TF activity in patients with TF expression in vascular cells and with elevated levels of circulating TF may decrease thrombosis associated with a variety of diseases... - Tissue factor in hemostasis and thrombosisRachel Tilley
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
Semin Thromb Hemost 32:5-10. 2006..TF expression in these diseases is associated with thrombotic events. Future therapeutic strategies may prove beneficial in the treatment of thrombosis. However, these strategies should be designed to avoid compromising hemostasis... - Genetic susceptibility to thrombosisJames P Luyendyk
Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, CVN-18, La Jolla, CA 92037, USA
Curr Atheroscler Rep 8:193-7. 2006..Tissue factor is the primary cellular initiator of blood coagulation and is a major contributor to thrombosis. In this review, we discuss the association between various polymorphisms and the risk for thrombosis... - Tissue factor and thrombin mediate myocardial ischemia-reperfusion injuryAlbert J Chong
Division of Cardiothoracic Surgery, The University of Washington, Seattle, Washington 98104, USA
Ann Thorac Surg 75:S649-55. 2003..However, defibrinogenating rabbits with ancrod had no effect on infarct size, suggesting a requirement of thrombin generation but not fibrin deposition in myocardial I/R injury...
Research Grants
- BLOOD COAGULATION & FIBRINOLYSISNigel Mackman; Fiscal Year: 2004..Dr. Housman is an acknowledged expert in human genomics. Taken together, the individual projects and the collaborative efforts promise to provide important insight into the molecular basis of cardiac hemostasis. ..
- Thrombin-PAR-1 Signaling in Cardiac I/R InjuryNigel Mackman; Fiscal Year: 2005..Our studies should increase the fundamental knowledge of the role of the thrombin-PAR-1 signaling pathway in myocardial I/R injury and may lead to the development of novel therapies to preserve ischemic myocardium. ..
- REGULATION OF INDUCIBLE GENE EXPRESSION IN MONOCYTESNigel Mackman; Fiscal Year: 2005..The clinical relevance of these studies is that they may provide new insight that can be used to develop improved therapeutic strategies for the treatment of patients with severe sepsis. ..
- Role of PAR-1 and PAR-2 in Cardiac RemodelingNigel Mackman; Fiscal Year: 2007..The results may lead to the development of PAR-1 and PAR-2 inhibitors that may be used as novel therapies for the treatment of pathological cardiac remodeling and hypertrophy in humans. ..
- REGULATION OF INDUCIBLE GENE EXPRESSION IN MONOCYTESNigel Mackman; Fiscal Year: 2007..These studies will provide new insight into the role of TF and the PI3K-Akt pathway in endotoxemia. This information can be used to develop improved therapeutic strategies for the treatment of patients with severe sepsis. ..
- REGULATION OF INDUCIBLE GENE EXPRESSION IN MONOCYTESNigel Mackman; Fiscal Year: 2009..These studies will provide new insight into the role of TF and the PI3K-Akt pathway in endotoxemia. This information can be used to develop improved therapeutic strategies for the treatment of patients with severe sepsis. ..
- Role of PAR-1 and PAR-2 in Cardiac RemodelingNigel Mackman; Fiscal Year: 2010..The results may lead to the development of PAR-1 and PAR-2 inhibitors that may be used as novel therapies for the treatment of pathological cardiac remodeling and hypertrophy in humans. ..
- TISSUE FACTOR GENE REGULATION IN MONOCYTESNigel Mackman; Fiscal Year: 1993..Understanding the transcriptional control of the TF gene should allow the development of effective strategies for the prevention and treatment of thrombotic and vascular diseases...
- REGULATION OF INDUCIBLE GENE EXPRESSION IN MONOCYTESNigel Mackman; Fiscal Year: 2000..Finally the applicant will use proteasome inhibitors to block NF-(B /Rel activity in a novel mouse sepsis model humanized for TF. ..
- INHIBITION OF GENE EXPRESSION IN ENDOTHELIAL CELLSNigel Mackman; Fiscal Year: 2001..The effects of intracellular cAMP on the functional activity and phosphorylation of NFKB/Rel proteins will be investigated. A yeast two hybrid system will be used to identify additional factors which interact with NFKB. ..
- Mechanisms of Venous Thromboembolism in CancerNIGEL contact MACKMAN; Fiscal Year: 2010..This is of enormous importance as physicians will be able to institute measures to prevent thrombosis in high-risk patients and improve clinical outcomes. ..