Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form
As of April 1st VIVO Scientific Profiles will no longer updated for faculty, and the link to VIVO will be removed from the library website. Faculty profile pages will continue to be updated via Interfolio. VIVO will continue being used behind the scenes to update graduate student profiles. Please contact helplib@scripps.edu if you have questions.
How to download citations from VIVO | Alternative profile options
Mackman, Nigel
Publications in VIVO
 
    Export Publications Table
co-author
Co-author Network
map of science
Map of Science

Mackman, Nigel

Faculty Member Adjunct
share the uri qr icon Close

Positions

  • 2011 - Director, UNC McAllister Heart Institute (MHI) , The University of North Carolina at Chapel Hill
  • 2007 - John Parker Distinguished Professor of Medicine, The University of North Carolina at Chapel Hill
  • 2007 - Co-Director of the Thrombosis and Hemostasis Program, The University of North Carolina at Chapel Hill
  • 2017 - 2018 Professor Adjunct, Immunology and Microbiology , Scripps Research
  • 2007 - 2017 Professor Adjunct, Immunology and Microbial Science (IMS) , Scripps Research
  • 2009 - 2011 Associate Director, UNC McAllister Heart Institute (MHI) , The University of North Carolina at Chapel Hill
  • 2002 - 2007 Associate Professor (with tenure), Department of Immunology, Scripps Research
  • 1995 - 2002 Associate Professor, Department of Immunology, Scripps Research
  • 1989 - 1995 Assistant Professor, Department of Immunology, Scripps Research
  • 1987 - 1989 Postdoctoral Fellow, Scripps Clinic and Research Foundation
  • 1985 - 1987 Postdoctoral Fellow, University of Leicester

Research Focus

Crosstalk Between the Coagulation Protease Cascade and the Inflammatory Response

My laboratory studies the crosstalk between the coagulation protease cascade and inflammation. We have shown that bacterial LPS induces human monocytes to express the procoagulant protein tissue factor (TF) and inflammatory mediators, such as TNF . We use human monocytic cell lines and human monocytes to elucidate the positive and negative regulatory intracellular signaling networks and transcription factors that control expression of these procoagulant and inflammatory genes. In addition, we generate transgenic mice to examine the role of these proteins in in vivo models of disease. My laboratory is interested in elucidating how coagulation proteases contribute to inflammation in sepsis and in ischemia-reperfusion (I/R) injury. We hypothesize that in sepsis the coagulation proteases, factor Xa and thrombin, increase the expression of inflammatory mediators by activating protease activator receptors (PARs) that are expressed on endothelial cells. Recently, we showed that TF-dependent thrombin generation contributed to myocardial infarction by increasing the expression of inflammatory mediators in a rabbit model of cardiac I/R injury. We have extended these studies by establishing a mouse model of cardiac I/R injury. Using PAR-1-/- mice, we have found that PAR-1 contributes to infarct size probably via activation by thrombin. In future studies, we will generate transgenic mice that express PAR-1 on either endothelial cells or cardiomyocytes to determine the site of functional PAR-1 expression that contributes to cardiac I/R injury. Other studies will elucidate the mechanism by which PAR-1 contributes to cardiac I/R injury.

  • Publications
  • Background
  • Contact
  • View All
scroll to property group menus

Publications

recent publications

  • academic article

    • Yokota, N., Zarpellon, A., Chakrabarty, S., Bogdanov, V. Y., Gruber, A., Castellino, F. J., Mackman, N., Ellies, L. G., Weiler, H., Ruggeri, Z. M., Ruf, W. Contributions of thrombin targets to tissue factor-dependent metastasis in hyperthrombotic mice Journal of Thrombosis and Haemostasis  2014 12:71-81  DOI:10.1111/jth.12442  PMID:24175924  PMCID:PMC3947224
    • Owens, A. P., Passam, F. H., Antoniak, S., Marshall, S. M., McDaniel, A. L., Rudel, L., Williams, J. C., Hubbard, B. K., Dutton, J. A., Wang, J. G., Tobias, P. S., Curtiss, L. K., et al. Monocyte tissue factor-dependent activation of coagulation in hypercholesterolemic mice and monkeys is inhibited by simvastatin Journal of Clinical Investigation  2012 122:558-568  DOI:10.1172/jci58969  PMID:22214850  PMCID:PMC3266787
    • Liu, Y., Jiang, P. F., Capkova, K., Xue, D., Ye, L. W., Sinha, S. C., Mackman, N., Janda, K. D., Liu, C. Tissue factor-activated coagulation cascade in the tumor microenvironment is critical for tumor progression and an effective target for therapy Cancer Research  2011 71:6492-6502  DOI:10.1158/0008-5472.can-11-1145  PMID:21880589
    • Redecha, P., Franzke, C. W., Ruf, W., Mackman, N., Girardi, G. Neutrophil activation by the tissue factor/factor viia/par2 axis mediates fetal death in a mouse model of anti phospholipid syndrome Journal of Clinical Investigation  2008 118:3453-3461  DOI:10.1172/jci36089  PMID:18802482  PMCID:PMC2542852
    • Bhattacharjee, G., Ahamed, J., Pawlinski, R., Liu, C., Mackman, N., Ruf, W., Edgington, T. S. Factor xa binding to annexin 2 mediates signal transduction via protease-activated receptor 1 Circulation Research  2008 102:457-464  DOI:10.1161/circresaha.107.167759  PMID:18174463  PMCID:PMC2838720
    • Kerschen, E. J., Fernandez, J. A., Cooley, B. C., Yang, X. V., Sood, R., Mosnier, L. O., Castellino, F. J., Mackman, N., Griffin, J. H., Weiler, H. Endotoxemia and sepsis mortality reduction by non-anticoagulant activated protein C Journal of Experimental Medicine  2007 204:2439-2448  DOI:10.1084/jem.20070404  PMID:17893198  PMCID:PMC2118455
    • Shigeoka, A. A., Holscher, T. D., King, A. J., Hallt, F. W., Kiosses, W. B., Tobias, P. S., Mackman, N., McKay, D. B. Tlr2 is constitutively expressed within the kidney and participates in ischemic renal injury through both myd88-dependent and -independent pathways Journal of Immunology  2007 178:6252-6258  PMID:17475853
    • Tilley, R. E., Pedersen, B., Pawlinski, R., Sato, Y., Erlich, J. H., Shen, Y. C., Day, S., Huang, Y., Eitzman, D. T., Boisvert, W. A., Curtiss, L. K., Fay, W. P., et al. Atherosclerosis in mice is not affected by a reduction in tissue factor expression Arteriosclerosis, Thrombosis, and Vascular Biology  2006 26:555-562  DOI:10.1161/01.ATV.0000202028.62414.3c  PMID:16385085
    • Bhattacharjee, G., Ahamed, J., Pedersen, B., El-Sheikh, A., Mackman, N., Ruf, W., Liu, C., Edgington, T. S. Regulation of tissue factor-mediated initiation of the coagulation cascade by cell surface grp78 Arteriosclerosis, Thrombosis, and Vascular Biology  2005 25:1737-1743  DOI:10.1161/01.atv.0000173419.31242.56  PMID:15947236
    • Arbibe, L., Mira, J. P., Teusch, N., Kline, L., Guha, M., Mackman, N., Godowski, P. J., Ulevitch, R. J., Knaus, U. G. Toll-like receptor 2-mediated nf-kappa b activation requires a raci-dependent pathway Nature Immunology  2000 1:533-540  DOI:10.1038/82797  PMID:11101877
    • Erlich, J., Fearns, C., Mathison, J., Ulevitch, R. J., Mackman, N. Lipopolysaccharide induction of tissue factor expression in rabbits Infection and Immunity  1999 67:2540-2546  PMID:10225918  PMCID:PMC116001
    • Bohuslav, J., Kravchenko, V. V., Parry, G. C. N., Erlich, J. H., Gerondakis, S., Mackman, N., Ulevitch, R. J. Regulation of an essential innate immune response by the p50 subunit of NF-kappa B Journal of Clinical Investigation  1998 102:1645-1652  DOI:10.1172/jci3877  PMID:9802878
    • Fowler, B., Mackman, N., Parmer, R. J., Miles, L. A. Binding of human single chain urokinase to Chinese hamster ovary cells and cloning of hamster u-PAR Thrombosis and Haemostasis  1998 80:148-154  PMID:9684801
    • Yao, J., Mackman, N., Edgington, T. S., Fan, S. T. Lipopolysaccharide induction of the tumor necrosis factor-alpha promoter in human monocytic cells - regulation by egr-1, c-jun, and nf-kappa b transcription factors Journal of Biological Chemistry  1997 272:17795-17801  DOI:10.1074/jbc.272.28.17795  PMID:9211933
    • Carmeliet, P., Mackman, N., Moons, L., Luther, T., Gressens, P., VanVlaenderen, I., Demunck, H., Kasper, M., Breier, G., Evrard, P., Muller, M., Risau, W., et al. Role of tissue factor in embryonic blood vessel development Nature  1996 383:73-75  DOI:10.1038/383073a0  PMID:8779717
    • GonzalezDunia, D., Eddleston, M., Mackman, N., Carbone, K., delaTorre, J. C. Expression of tissue factor is increased in astrocytes within the central nervous system during persistent infection with Borna disease virus Journal of Virology  1996 70:5812-5820  PMID:8709198  PMCID:PMC190596
    • Luther, T., Flossel, C., Mackman, N., Bierhaus, A., Kasper, M., Albrecht, S., Sage, E. H., Iruela-Arispe, L., Grossmann, H., Strohlein, A., Zhang, Y., Nawroth, P. P., et al. Tissue factor expression during human and mouse development American Journal of Pathology  1996 149:101-113  PMID:8686734  PMCID:PMC1865244
    • Tipping, P. G., Erlich, J. H., Apostolopoulos, J., Mackman, N., Loskutoff, D., Holdsworth, S. R. Glomerular tissue factor expression in crescentic glomerulonephritis. Correlations between antigen, activity, and mRNA American Journal of Pathology  1995 147:1736-1748  PMID:7495298  PMCID:PMC1869967
    • Olman, M. A., Mackman, N., Gladson, C. L., Moser, K. M., Loskutoff, D. J. Changes in procoagulant and fibrinolytic gene expression during bleomycin-induced lung injury in the mouse Journal of Clinical Investigation  1995 96:1621-1630  DOI:10.1172/jci118201  PMID:7544811  PMCID:PMC185788
    • Fan, S. T., Mackman, N., Cui, M. Z., Edgington, T. S. Integrin regulation of an inflammatory effector gene - direct induction of the tissue factor promoter by engagement of beta-1 or alpha-4 integrin chains Journal of Immunology  1995 154:3266-3274  PMID:7534794
    • Quirk, S. M., Pentecost, B. T., Mackman, N., Loskutoff, D. J., Hartzell, S., Henrikson, K. P. The regulation of uterine tissue factor by estrogen Endocrine  1995 3:177-184  DOI:10.1007/bf02990070  PMID:21153155
    • Steinemann, S., Ulevitch, R. J., Mackman, N. Role of the lipopolysaccharide (lps)-binding protein cd14 pathway in lps induction of tissue factor expression in monocytic cells Arteriosclerosis and Thrombosis  1994 14:1202-1209  PMID:7517185
    • Brand, K., Banka, C. L., Mackman, N., Terkeltaub, R. A., Fan, S. T., Curtiss, L. K. Oxidized ldl enhances lipopolysaccharide-induced tissue factor expression in human adherent monocytes Arteriosclerosis and Thrombosis  1994 14:790-797  PMID:8172855
    • Cui, M. Z., Parry, G. C. N., Edgington, T. S., Mackman, N. Regulation of tissue factor gene-expression in epithelial-cells - induction by serum and phorbol 12-myristate 13-acetate Arteriosclerosis and Thrombosis  1994 14:807-814  PMID:8172857
    • Lee, J. D., Kravchenko, V., Kirkland, T. N., Han, J., Mackman, N., Moriarty, A., Leturcq, D., Tobias, P. S., Ulevitch, R. J. Glycosyl-phosphatidylinositol-anchored or integral membrane forms of CD14 mediate identical cellular responses to endotoxin Proceedings of the National Academy of Sciences of the United States of America  1993 90:9930-9934  DOI:10.1073/pnas.90.21.9930  PMID:7694296  PMCID:PMC47686
    • Eddleston, M., Delatorre, J. C., Oldstone, M. B. A., Loskutoff, D. J., Edgington, T. S., Mackman, N. Astrocytes are the primary source of tissue factor in the murine central nervous system. A role for astrocytes in cerebral hemostasis Journal of Clinical Investigation  1993 92:349-358  DOI:10.1172/jci116573  PMID:8326003  PMCID:PMC293611
    • Mackman, N., Sawdey, M. S., Keeton, M. R., Loskutoff, D. J. Murine tissue factor gene expression in vivo. Tissue and cell specificity and regulation by lipopolysaccharide American Journal of Pathology  1993 143:76-84  PMID:8317556  PMCID:PMC1886940
    • Brand, K., Mackman, N., Curtiss, L. K. Interferon-gamma inhibits macrophage apolipoprotein-e production by posttranslational mechanisms Journal of Clinical Investigation  1993 91:2031-2039  DOI:10.1172/jci116425  PMID:8486772
    • Fan, S. T., Brian, A. A., Lollo, B. A., Mackman, N., Shen, N. L., Edgington, T. S. Cd11a/cd18 (lfa-1) integrin engagement enhances biosynthesis of early cytokines by activated t-cells Cellular Immunology  1993 148:48-59  DOI:10.1006/cimm.1993.1090  PMID:8098668
    • Ollivier, V., Houssaye, S., Ternisien, C., Leon, A., Deverneuil, H., Elbim, C., Mackman, N., Edgington, T. S., Deprost, D. Endotoxin-induced tissue factor messenger-rna in human monocytes is negatively regulated by a cyclic amp-dependent mechanism Blood  1993 81:973-979  PMID:7679011
    • Edgington, T. S., Mackman, N., Fan, S. T., Ruf, W. Cellular immune and cytokine pathways resulting in tissue factor expression and relevance to septic shock Nouvelle Revue Francaise d Hematologie  1992 34:S15-S27  PMID:1364116
    • Mackman, N., Brand, K., Edgington, T. S. Lipopolysaccharide-mediated transcriptional activation of the human tissue factor gene in thp-1 monocytic cells requires both activator protein-1 and nuclear factor-kappa-b binding-sites Journal of Experimental Medicine  1991 174:1517-1526  DOI:10.1084/jem.174.6.1517  PMID:1744583
    • Brand, K., Fowler, B. J., Edgington, T. S., Mackman, N. Tissue factor messenger-rna in thp-1 monocytic cells is regulated at both transcriptional and posttranscriptional levels in response to lipopolysaccharide Molecular and Cellular Biology  1991 11:4732-4738  PMID:1875949  PMCID:PMC361371
    • Edgington, T. S., Mackman, N., Brand, K., Ruf, W. The structural biology of expression and function of tissue factor Thrombosis and Haemostasis  1991 66:67-79  PMID:1833852
    • Andrews, B. S., Rehemtulla, A., Fowler, B. J., Edgington, T. S., Mackman, N. Conservation of tissue factor primary sequence among 3 mammalian-species Gene  1991 98:265-269  DOI:10.1016/0378-1119(91)90184-d  PMID:1840552
    • Mackman, N., Fowler, B. J., Edgington, T. S., Morrissey, J. H. Functional-analysis of the human tissue factor promoter and induction by serum Proceedings of the National Academy of Sciences of the United States of America  1990 87:2254-2258  DOI:10.1073/pnas.87.6.2254  PMID:2315317
    • Mackman, N., Morrissey, J. H., Fowler, B., Edgington, T. S. Complete sequence of the human-tissue factor gene, a highly regulated cellular receptor that initiates the coagulation protease cascade Biochemistry  1989 28:1755-1762  DOI:10.1021/bi00430a050  PMID:2719931
scroll to property group menus

Background

education and training

  • Ph.D. in Genetics, University of Leicester 1982 - 1985
  • B.Sc. in Molecular Biology, University of Leicester 1978 - 1982
scroll to property group menus

Contact

full name

  • Nigel Mackman

geographic location

  • Scripps California 

©2022 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support