Jacek J. Hawiger, M.D., Ph.D.

Distinguished Professor

jack.hawiger@vanderbilt.edu
Faculty Appointments
Distinguished Professor of Medicine Professor of Molecular Physiology and BiophysicsLouise B. McGavock Chair
Education
M.D., Copernicus School of Medicine, Cracow, PolandM.A., Harvard University, Cambridge, MassachusettsPh.D., Medical Microbiology, National Institute of Public Health , Warsaw, PolandM.D., Medicine, Copernicus School of Medicine, Cracow, Poland
Office Address
1161 21st Ave. South, T-2222 MCN, Nashville, TN
Nashville, TN 37232-2363
Research Description
Inflammation is the main mechanism of diseases caused by microbial, autoimmune, metabolic, and physical factors. In fact, we estimate that approx. 80% of all major human diseases, including heart attacks, strokes, sepsis, and early cancer, are mediated by inflammation. Proinflammatory cues are sensed by pattern recognition receptors such as Toll-like Receptors (TLRs) that are mainstays of innate immunity. These receptors generate signals that are transduced to the nucleus by an intricate network of intracellular adaptors. We study two families of these adaptors as potential targets for anti-inflammatory therapy to prevent reprogramming of the genome toward proinflammatory phenotype.

The first family of innate immunity adaptors of intense interest is MyD88 (myeloid differentiation 88) protein and its four relatives, including MAL, TRIF and SARM. We study them by identifying their cross-talk with TLRs and with each other. For example, we identified the RDR motif in Box 2 of MyD88 TIR domain as the interactive site with some members of TLR superfamily. This site is mutated in inborn errors of innate immunity characterized by pyogenic infections. We also unraveled a new function for another adaptor SARM.

The second family of adaptors of longstanding interest to us is the so-called nuclear import machinery, known as importins or karyopherins. We provided initial evidence that by targeting them with cell-penetrating peptides, which displace nuclear import cargo from its binding pocket on importin alpha 1, we prevent nuclear delivery of proinflammatory transcription factors such as NFkappa B, AP-1, NFAT, and STAT-1. Hence, proinflammatory reprogramming of the genome is prevented in multiple cells that stop producing inflammatory, procoagulant, proapoptotic, and autoimmune mediators. We accomplished this outcome by developing an innovative platform for intracellular delivery of peptides and proteins that bypass endosomal pathway with its degradative potential. We have proven the utility of nuclear import inhibitors as cell-penetrating peptides in preclinical models of septic/toxic shock and in acute lung inflammation caused by bacterial lipopolysaccharide and superantigen as well as in chronic autoimmune diabetes model that mimics Type 1 diabetes. We extended these long-term treatment studies to a relevant model of atherosclerosis induced by Western diet in LDL receptor-negative mice. Cumulatively, these basic and translational studies provided a firm basis for the nuclear paradigm of inflammation

Finally, we continue our groundbreaking studies of intracellular protein therapy as a facile alternative of gene therapy. We have proven the utility of intracellular protein therapy by bioengineering and delivering physiologic suppressor of cytokine signaling 3 (SOCS3) to prevent or treat acute liver inflammation and apoptosis induced by microbial agents in preclinical models. We extended the anti-inflammatory action of cell-penetrating SOCS3 by engineering its long-acting form to persist 41 times longer than endogenous SOCS3. This increased stability, coupled with the capacity for rapid intracellular delivery renders the CP- SOCS3 mutant an attractive candidate for intracellular protein therapy to suppress acute and chronic inflammation induced by a variety of proinflammatory agonists in multiple organ systems.
Research Keywords
Inflammation, Innate Immunity, Biodefense, and Intracellular Delivery of Proteins and Peptides
Publications
Wynn JL, Wilson CS, Hawiger J, Scumpia PO, Marshall AF, Liu JH, Zharkikh I, Wong HR, Lahni P, Benjamin JT, Plosa EJ, Weitkamp JH, Sherwood ER, Moldawer LL, Ungaro R, Baker HV, Lopez MC, McElroy SJ, Colliou N, Mohamadzadeh M, Moore DJ. Targeting IL-17A attenuates neonatal sepsis mortality induced by IL-18. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2016 May 5/10/2016; 113(19): E2627-35. PMID: 27114524, PII: 1515793113, DOI: 10.1073/pnas.1515793113, ISSN: 1091-6490.

Hawiger J, Veach RA, Zienkiewicz J. New paradigms in sepsis: from prevention to protection of failing microcirculation. J. Thromb. Haemost [print-electronic]. 2015 Oct; 13(10): 1743-56. PMID: 26190521, DOI: 10.1111/jth.13061, ISSN: 1538-7836.

Qiao H, Liu Y, Veach RA, Wylezinski L, Hawiger J. The adaptor CRADD/RAIDD controls activation of endothelial cells by proinflammatory stimuli. J. Biol. Chem [print-electronic]. 2014 Aug 8/8/2014; 289(32): 21973-83. PMID: 24958727, PMCID: PMC4139214, PII: M114.588723, DOI: 10.1074/jbc.M114.588723, ISSN: 1083-351X.

DiGiandomenico A, Veach RA, Zienkiewicz J, Moore DJ, Wylezinski LS, Hutchens MA, Hawiger J. The "genomic storm" induced by bacterial endotoxin is calmed by a nuclear transport modifier that attenuates localized and systemic inflammation. PLoS ONE. 2014; 9(10): e110183. PMID: 25329889, PMCID: PMC4203769, PII: PONE-D-14-26863, DOI: 10.1371/journal.pone.0110183, ISSN: 1932-6203.

Zienkiewicz J, Armitage A, Hawiger J. Targeting nuclear import shuttles, importins/karyopherins alpha by a peptide mimicking the NF¿B1/p50 nuclear localization sequence. J Am Heart Assoc. 2013 Oct; 2(5): e000386. PMID: 24042087, PMCID: PMC3835248, PII: jah3309, DOI: 10.1161/JAHA.113.000386, ISSN: 2047-9980.

Liu Y, Major AS, Zienkiewicz J, Gabriel CL, Veach RA, Moore DJ, Collins RD, Hawiger J. Nuclear transport modulation reduces hypercholesterolemia, atherosclerosis, and fatty liver. J Am Heart Assoc. 2013 Apr; 2(2): e000093. PMID: 23563994, PMCID: PMC3647260, PII: 2/2/e000093, DOI: 10.1161/JAHA.113.000093, ISSN: 2047-9980.

Sethman CR, Hawiger J. The innate immunity adaptor SARM translocates to the nucleus to stabilize lamins and prevent DNA fragmentation in response to pro-apoptotic signaling. PLoS ONE [electronic-print]. 2013; 8(7): e70994. PMID: 23923041, PMCID: PMC3726548, PII: PONE-D-13-19251, DOI: 10.1371/journal.pone.0070994, ISSN: 1932-6203.

Lin Q, Liu Y, Moore DJ, Elizer SK, Veach RA, Hawiger J, Ruley HE. Cutting edge: the "death" adaptor CRADD/RAIDD targets BCL10 and suppresses agonist-induced cytokine expression in T lymphocytes. J. Immunol [print-electronic]. 2012 Mar 3/15/2012; 188(6): 2493-7. PMID: 22323537, PMCID: PMC3294148, PII: jimmunol.1101502, DOI: 10.4049/jimmunol.1101502, ISSN: 1550-6606.

Veach RA, Zienkiewicz J, Collins RD, Hawiger J. Lethality in a murine model of pulmonary anthrax is reduced by combining nuclear transport modifier with antimicrobial therapy. PLoS ONE [print-electronic]. 2012; 7(1): e30527. PMID: 22291977, PMCID: PMC3266913, PII: PONE-D-11-13071, DOI: 10.1371/journal.pone.0030527, ISSN: 1932-6203.

Hawiger J, Musser JM. How to approach genome wars in sepsis? [editorial]. Crit Care [print-electronic]. 2011; 15(6): 1007. PMID: 22136332, PMCID: PMC3388672, PII: cc10482, DOI: 10.1186/cc10482, ISSN: 1466-609X.

Fletcher TC, DiGiandomenico A, Hawiger J. Extended anti-inflammatory action of a degradation-resistant mutant of cell-penetrating suppressor of cytokine signaling 3. J. Biol. Chem [print-electronic]. 2010 Jun 6/11/2010; 285(24): 18727-36. PMID: 20400504, PMCID: PMC2881796, PII: M109.095216, DOI: 10.1074/jbc.M109.095216, ISSN: 1083-351X.

Moore DJ, Zienkiewicz J, Kendall PL, Liu D, Liu X, Veach RA, Collins RD, Hawiger J. In vivo islet protection by a nuclear import inhibitor in a mouse model of type 1 diabetes. PLoS ONE. 2010; 5(10): e13235. PMID: 20949090, PMCID: PMC2950856, DOI: 10.1371/journal.pone.0013235, ISSN: 1932-6203.

Liu D, Zienkiewicz J, DiGiandomenico A, Hawiger J. Suppression of acute lung inflammation by intracellular peptide delivery of a nuclear import inhibitor. Mol. Ther [print-electronic]. 2009 May; 17(5): 796-802. PMID: 19259070, PMCID: PMC2835128, PII: mt200918, DOI: 10.1038/mt.2009.18, ISSN: 1525-0024.

DiGiandomenico A, Wylezinski LS, Hawiger J. Intracellular delivery of a cell-penetrating SOCS1 that targets IFN-gamma signaling. Sci Signal. 2009; 2(80): ra37. PMID: 19622834, PMCID: PMC2798805, PII: 2/80/ra37, DOI: 10.1126/scisignal.1162191, ISSN: 1937-9145.

Zanchi C, Zoja C, Morigi M, Valsecchi F, Liu XY, Rottoli D, Locatelli M, Buelli S, Pezzotta A, Mapelli P, Geelen J, Remuzzi G, Hawiger J. Fractalkine and CX3CR1 mediate leukocyte capture by endothelium in response to Shiga toxin. J. Immunol. 2008 Jul 7/15/2008; 181(2): 1460-9. PMID: 18606701, PII: 181/2/1460, ISSN: 1550-6606.

Bezbradica JS, Gordy LE, Stanic AK, Dragovic S, Hill T, Hawiger J, Unutmaz D, Van Kaer L, Joyce S. Granulocyte-macrophage colony-stimulating factor regulates effector differentiation of invariant natural killer T cells during thymic ontogeny. Immunity [print-electronic]. 2006 Sep; 25(3): 487-97. PMID: 16949316, PII: S1074-7613(06)00376-1, DOI: 10.1016/j.immuni.2006.06.017, ISSN: 1074-7613.

Jo D, Liu D, Yao S, Collins RD, Hawiger J. Intracellular protein therapy with SOCS3 inhibits inflammation and apoptosis. Nat. Med [print-electronic]. 2005 Aug; 11(8): 892-8. PMID: 16007096, PII: nm1269, DOI: 10.1038/nm1269, ISSN: 1078-8956.

Li C, Zienkiewicz J, Hawiger J. Interactive sites in the MyD88 Toll/interleukin (IL) 1 receptor domain responsible for coupling to the IL1beta signaling pathway. J. Biol. Chem [print-electronic]. 2005 Jul 7/15/2005; 280(28): 26152-9. PMID: 15849357, PII: M503262200, DOI: 10.1074/jbc.M503262200, ISSN: 0021-9258.

Kathy Aschheim, Nadia Cervoni, Laura DeFrancesco, Teresa Moogan and Gaspar Taroncher-Oldenburg. New septic shock therapeutic? [editorial]. Nature Biotechnology. 2005; 23((8)): 949.

Melissa Marino. Protein therapy "SOCS" in to inflammation [editorial]. The Reporter/VUMC. 2005; ((August 19)).

Liu D, Li C, Chen Y, Burnett C, Liu XY, Downs S, Collins RD, Hawiger J. Nuclear import of proinflammatory transcription factors is required for massive liver apoptosis induced by bacterial lipopolysaccharide. J. Biol. Chem [print-electronic]. 2004 Nov 11/12/2004; 279(46): 48434-42. PMID: 15345713, PII: M407190200, DOI: 10.1074/jbc.M407190200, ISSN: 0021-9258.

Liu D, Liu XY, Robinson D, Burnett C, Jackson C, Seele L, Veach RA, Downs S, Collins RD, Ballard DW, Hawiger J. Suppression of Staphylococcal Enterotoxin B-induced Toxicity by a Nuclear Import Inhibitor. J. Biol. Chem [print-electronic]. 2004 Apr 4/30/2004; 279(18): 19239-46. PMID: 14732709, PII: M313442200, DOI: 10.1074/jbc.M313442200, ISSN: 0021-9258.

Veach RA, Liu D, Yao S, Chen Y, Liu XY, Downs S, Hawiger J. Receptor/transporter-independent targeting of functional peptides across the plasma membrane. J. Biol. Chem [print-electronic]. 2004 Mar 3/19/2004; 279(12): 11425-31. PMID: 14699109, PII: M311089200, DOI: 10.1074/jbc.M311089200, ISSN: 0021-9258.

Hawiger J. Peptide/Protein Delivery. 2002.

Hawiger J. Innate immunity and inflammation: a transcriptional paradigm. Immunol. Res. 2001; 23(2-3): 99-109. PMID: 11444396, PII: IR:23:2-3:099, DOI: 10.1385/IR:23:2-3:099, ISSN: 0257-277X.

Oltz EM, Hawiger J. Immunology at Vanderbilt University. Immunol. Res. 2001; 23(2-3): 97-8. PMID: 11444395, PII: IR:23:2-3:097, DOI: 10.1385/IR:23:2-3:097, ISSN: 0257-277X.

Liu XY, Robinson D, Veach RA, Liu D, Timmons S, Collins RD, Hawiger J. Peptide-directed suppression of a pro-inflammatory cytokine response. J. Biol. Chem. 2000 Jun 6/2/2000; 275(22): 16774-8. PMID: 10751381, PII: C000083200, DOI: 10.1074/jbc.C000083200, ISSN: 0021-9258.

Ware S, Donahue JP, Hawiger J, Anderson WF. Structure of the fibrinogen gamma-chain integrin binding and factor XIIIa cross-linking sites obtained through carrier protein driven crystallization. Protein Sci. 1999 Dec; 8(12): 2663-71. PMID: 10631982, PMCID: PMC2144222, DOI: 10.1110/ps.8.12.2663, ISSN: 0961-8368.

Hawiger J, Veach RA, Liu XY, Timmons S, Ballard DW. IkappaB kinase complex is an intracellular target for endotoxic lipopolysaccharide in human monocytic cells. Blood. 1999 Sep 9/1/1999; 94(5): 1711-6. PMID: 10477696, ISSN: 0006-4971.

Hawiger J. Noninvasive intracellular delivery of functional peptides and proteins. Curr Opin Chem Biol. 1999 Feb; 3(1): 89-94. PMID: 10021415, PII: S1367-5931(99)80016-7, ISSN: 1367-5931.

Torgerson TR, Colosia AD, Donahue JP, Lin YZ, Hawiger J. Regulation of NF-kappa B, AP-1, NFAT, and STAT1 nuclear import in T lymphocytes by noninvasive delivery of peptide carrying the nuclear localization sequence of NF-kappa B p50. J. Immunol. 1998 Dec 12/1/1998; 161(11): 6084-92. PMID: 9834092, ISSN: 0022-1767.

Zhang L, Torgerson TR, Liu XY, Timmons S, Colosia AD, Hawiger J, Tam JP. Preparation of functionally active cell-permeable peptides by single-step ligation of two peptide modules. Proc. Natl. Acad. Sci. U.S.A. 1998 Aug 8/4/1998; 95(16): 9184-9. PMID: 9689055, PMCID: PMC21313, ISSN: 0027-8424.

Chu ZL, DiDonato JA, Hawiger J, Ballard DW. The tax oncoprotein of human T-cell leukemia virus type 1 associates with and persistently activates IkappaB kinases containing IKKalpha and IKKbeta. J. Biol. Chem. 1998 Jun 6/26/1998; 273(26): 15891-4. PMID: 9632633, ISSN: 0021-9258.

Hawiger J. Cellular import of functional peptides to block intracellular signaling. Curr. Opin. Immunol. 1997 Apr; 9(2): 189-94. PMID: 9099795, PII: S0952-7915(97)80134-3, ISSN: 0952-7915.

Liu XY, Timmons S, Lin YZ, Hawiger J. Identification of a functionally important sequence in the cytoplasmic tail of integrin beta 3 by using cell-permeable peptide analogs. Proc. Natl. Acad. Sci. U.S.A. 1996 Oct 10/15/1996; 93(21): 11819-24. PMID: 8876221, PMCID: PMC38142, ISSN: 0027-8424.

Lin YZ, Yao SY, Hawiger J. Role of the nuclear localization sequence in fibroblast growth factor-1-stimulated mitogenic pathways. J. Biol. Chem. 1996 Mar 3/8/1996; 271(10): 5305-8. PMID: 8621379, ISSN: 0021-9258.

Hawiger J. Mechanisms involved in platelet vessel wall interaction. Thromb. Haemost. 1995 Jul; 74(1): 369-72. PMID: 8578487, ISSN: 0340-6245.

Lin YZ, Yao SY, Veach RA, Torgerson TR, Hawiger J. Inhibition of nuclear translocation of transcription factor NF-kappa B by a synthetic peptide containing a cell membrane-permeable motif and nuclear localization sequence. J. Biol. Chem. 1995 Jun 6/16/1995; 270(24): 14255-8. PMID: 7782278, ISSN: 0021-9258.

Hawiger J. Adhesive ends of fibrinogen and its antiadhesive peptides: the end of a saga?. Semin. Hematol. 1995 Apr; 32(2): 99-109. PMID: 7652584, ISSN: 0037-1963.

Donald R, Ballard DW, Hawiger J. Proteolytic processing of NF-kappa B/I kappa B in human monocytes. ATP-dependent induction by pro-inflammatory mediators. J. Biol. Chem. 1995 Jan 1/6/1995; 270(1): 9-12. PMID: 7814425, ISSN: 0021-9258.

Donahue JP, Patel H, Anderson WF, Hawiger J. Three-dimensional structure of the platelet integrin recognition segment of the fibrinogen gamma chain obtained by carrier protein-driven crystallization. Proc. Natl. Acad. Sci. U.S.A. 1994 Dec 12/6/1994; 91(25): 12178-82. PMID: 7527555, PMCID: PMC45400, ISSN: 0027-8424.

Donahue JP, Sugg N, Hawiger J. The integrin alpha v gene: identification and characterization of the promoter region. Biochim. Biophys. Acta. 1994 Sep 9/13/1994; 1219(1): 228-32. PMID: 7522056, PII: 0167-4781(94)90278-X, ISSN: 0006-3002.

Shepherd JT, Bergan JJ, Cohen RA, Hawiger JJ, Hillis LD, Katzen BT, Mohr JP. Report of the Task Force on Vascular Medicine. Circulation. 1994 Jan; 89(1): 532-5. PMID: 8281694, ISSN: 0009-7322.

Read MA, Cordle SR, Veach RA, Carlisle CD, Hawiger J. Cell-free pool of CD14 mediates activation of transcription factor NF-kappa B by lipopolysaccharide in human endothelial cells. Proc. Natl. Acad. Sci. U.S.A. 1993 Nov 11/1/1993; 90(21): 9887-91. PMID: 7694295, PMCID: PMC47677, ISSN: 0027-8424.

Cordle SR, Donald R, Read MA, Hawiger J. Lipopolysaccharide induces phosphorylation of MAD3 and activation of c-Rel and related NF-kappa B proteins in human monocytic THP-1 cells. J. Biol. Chem. 1993 Jun 6/5/1993; 268(16): 11803-10. PMID: 8505309, ISSN: 0021-9258.

Blumenstein M, Matsueda GR, Timmons S, Hawiger J. A beta-turn is present in the 392-411 segment of the human fibrinogen gamma-chain. Effects of structural changes in this segment on affinity to antibody 4A5. Biochemistry. 1992 Nov 11/10/1992; 31(44): 10692-8. PMID: 1420184, ISSN: 0006-2960.

Hawiger J. Introduction to platelet structural and functional organization. Meth. Enzymol. 1992; 215: 3-5. PMID: 1435330, ISSN: 0076-6879.

Hawiger J, Timmons S. Binding of fibrinogen and von Willebrand factor to platelet glycoprotein IIb-IIIa complex. Meth. Enzymol. 1992; 215: 228-43. PMID: 1435324, ISSN: 0076-6879.

Hawiger J. Repertoire of platelet receptors. Meth. Enzymol. 1992; 215: 131-6. PMID: 1435318, ISSN: 0076-6879.

Chen CS, Hawiger J. Reactivity of synthetic peptide analogs of adhesive proteins in regard to the interaction of human endothelial cells with extracellular matrix. Blood. 1991 May 5/15/1991; 77(10): 2200-6. PMID: 1709375, ISSN: 0006-4971.

Shiba E, Lindon JN, Kushner L, Matsueda GR, Hawiger J, Kloczewiak M, Kudryk B, Salzman EW. Antibody-detectable changes in fibrinogen adsorption affecting platelet activation on polymer surfaces. Am. J. Physiol. 1991 May; 260(5 Pt 1): C965-74. PMID: 2035620, ISSN: 0002-9513.

Hawiger J. Adhesive interactions of platelets and their blockade. Ann. N. Y. Acad. Sci. 1991; 614: 270-8. PMID: 2024888, ISSN: 0077-8923.

Bauer KA, Kass BL, ten Cate H, Hawiger JJ, Rosenberg RD. Factor IX is activated in vivo by the tissue factor mechanism. Blood. 1990 Aug 8/15/1990; 76(4): 731-6. PMID: 2383653, ISSN: 0006-4971.

Grabarek J, Her GR, Reinhold VN, Hawiger J. Endotoxic lipid A interaction with human platelets. Structure-function analysis of lipid A homologs obtained from Salmonella minnesota Re595 lipopolysaccharide. J. Biol. Chem. 1990 May 5/15/1990; 265(14): 8117-21. PMID: 2335520, ISSN: 0021-9258.

Johnson RS, Her GR, Grabarek J, Hawiger J, Reinhold VN. Structural characterization of monophosphoryl lipid A homologs obtained from Salmonella minnesota Re595 lipopolysaccharide. J. Biol. Chem. 1990 May 5/15/1990; 265(14): 8108-16. PMID: 2335519, ISSN: 0021-9258.

Romano M, Hawiger J. Interaction of endotoxic lipid A and lipid X with purified human platelet protein kinase C. J. Biol. Chem. 1990 Jan 1/25/1990; 265(3): 1765-70. PMID: 2295655, ISSN: 0021-9258.

Bauer KA, Kass BL, ten Cate H, Bednarek MA, Hawiger JJ, Rosenberg RD. Detection of factor X activation in humans. Blood. 1989 Nov 11/1/1989; 74(6): 2007-15. PMID: 2804345, ISSN: 0006-4971.

Donaldson DJ, Mahan JT, Amrani D, Hawiger J. Fibrinogen-mediated epidermal cell migration: structural correlates for fibrinogen function. J. Cell. Sci. 1989 Sep; 94 ( Pt 1): 101-8. PMID: 2613766, ISSN: 0021-9533.

Timmons S, Bednarek MA, Kloczewiak M, Hawiger J. Antiplatelet "hybrid" peptides analogous to receptor recognition domains on gamma and alpha chains of human fibrinogen. Biochemistry. 1989 Apr 4/4/1989; 28(7): 2919-23. PMID: 2742820, ISSN: 0006-2960.

Kloczewiak M, Timmons S, Bednarek MA, Sakon M, Hawiger J. Platelet receptor recognition domain on the gamma chain of human fibrinogen and its synthetic peptide analogues. Biochemistry. 1989 Apr 4/4/1989; 28(7): 2915-9. PMID: 2742819, ISSN: 0006-2960.

Hawiger J, Kloczewiak M, Bednarek MA, Timmons S. Platelet receptor recognition domains on the alpha chain of human fibrinogen: structure-function analysis. Biochemistry. 1989 Apr 4/4/1989; 28(7): 2909-14. PMID: 2742818, ISSN: 0006-2960.

Weiss HJ, Hawiger J, Ruggeri ZM, Turitto VT, Thiagarajan P, Hoffmann T. Fibrinogen-independent platelet adhesion and thrombus formation on subendothelium mediated by glycoprotein IIb-IIIa complex at high shear rate. J. Clin. Invest. 1989 Jan; 83(1): 288-97. PMID: 2910912, PMCID: PMC303673, DOI: 10.1172/JCI113871, ISSN: 0021-9738.

Timmons S, Hawiger J. Isolation of human platelets by albumin gradient and gel filtration. Meth. Enzymol. 1989; 169: 11-21. PMID: 2716523, PII: 0076-6879(89)69046-5, ISSN: 0076-6879.

Hawiger J. Platelet secretory pathways: an overview. Meth. Enzymol. 1989; 169: 191-5. PMID: 2654559, PII: 0076-6879(89)69059-3, ISSN: 0076-6879.

Grabarek J, Timmons S, Hawiger J. Modulation of human platelet protein kinase C by endotoxic lipid A. J. Clin. Invest. 1988 Sep; 82(3): 964-71. PMID: 3047171, PMCID: PMC303609, DOI: 10.1172/JCI113705, ISSN: 0021-9738.

Kloczewiak M, Timmons S, Hawiger J. Reactivity of chemically cross-linked fibrinogen and its fragments D toward the staphylococcal clumping receptor. Biochemistry. 1987 Sep 9/22/1987; 26(19): 6152-6. PMID: 2961366, ISSN: 0006-2960.

Hawiger J. Dr. Mario Baldini (January 15, 1917-August 4, 1986). Thromb. Res. 1987 Jul 7/1/1987; 47(1): 1-3. PMID: 3310321, ISSN: 0049-3848.

Hawiger J. Formation and regulation of platelet and fibrin hemostatic plug. Hum. Pathol. 1987 Feb; 18(2): 111-22. PMID: 3804319, ISSN: 0046-8177.

Hawiger J. Macromolecules that link platelets following vessel wall injury. Ann. N. Y. Acad. Sci. 1987; 509: 131-41. PMID: 2827552, ISSN: 0077-8923.

Timmons S, Huzoor-Akbar, Grabarek J, Kloczewiak M, Hawiger J. Mechanism of human platelet activation by endotoxic glycolipid-bearing mutant Re595 of Salmonella minnesota. Blood. 1986 Nov; 68(5): 1015-23. PMID: 3768528, ISSN: 0006-4971.

McManama G, Lindon JN, Kloczewiak M, Smith MA, Ware JA, Hawiger J, Merrill EW, Salzman EW. Platelet aggregation by fibrinogen polymers crosslinked across the E domain. Blood. 1986 Aug; 68(2): 363-71. PMID: 3730607, ISSN: 0006-4971.

Timmons S, Hawiger J. Von Willebrand factor can substitute for plasma fibrinogen in ADP-induced platelet aggregation. Trans. Assoc. Am. Physicians. 1986; 99: 226-35. PMID: 3496699, ISSN: 0066-9458.

Timmons S, Kloczewiak M, Hawiger J. ADP-dependent common receptor mechanism for binding of von Willebrand factor and fibrinogen to human platelets. Proc. Natl. Acad. Sci. U.S.A. 1984 Aug; 81(15): 4935-9. PMID: 6087354, PMCID: PMC391607, ISSN: 0027-8424.

Nachman RL, Leung LL, Kloczewiak M, Hawiger J. Complex formation of platelet membrane glycoproteins IIb and IIIa with the fibrinogen D domain. J. Biol. Chem. 1984 Jul 7/10/1984; 259(13): 8584-8. PMID: 6234315, ISSN: 0021-9258.

Kloczewiak M, Timmons S, Lukas TJ, Hawiger J. Platelet receptor recognition site on human fibrinogen. Synthesis and structure-function relationship of peptides corresponding to the carboxy-terminal segment of the gamma chain. Biochemistry. 1984 Apr 4/10/1984; 23(8): 1767-74. PMID: 6326808, ISSN: 0006-2960.

Sakon M, Hawiger J. Mechanism triggering platelet hemostatic plug formation in vivo. Trans. Assoc. Am. Physicians. 1984; 97: 311-8. PMID: 6535347, ISSN: 0066-9458.

Hawiger J, Kloczewiak M, Timmons S, Strong D, Doolittle RF. Interaction of fibrinogen with staphylococcal clumping factor and with platelets. Ann. N. Y. Acad. Sci. 1983 Jun 6/27/1983; 408: 521-35. PMID: 6223560, ISSN: 0077-8923.

Huddleston CB, Lupinetti FM, Laws KH, Collins JC, Clanton JA, Hawiger JJ, Oates JA, Hammon JW. The effects of RO-22-4679, a thromboxane synthetase inhibitor, on ventricular fibrillation induced by coronary artery occlusion in conscious dogs. Circ. Res. 1983 May; 52(5): 608-13. PMID: 6682723, ISSN: 0009-7330.

FitzGerald GA, Oates JA, Hawiger J, Maas RL, Roberts LJ, Lawson JA, Brash AR. Endogenous biosynthesis of prostacyclin and thromboxane and platelet function during chronic administration of aspirin in man. J. Clin. Invest. 1983 Mar; 71(3): 676-88. PMID: 6338043, PMCID: PMC436917, ISSN: 0021-9738.

Kloczewiak M, Timmons S, Hawiger J. Recognition site for the platelet receptor is present on the 15-residue carboxy-terminal fragment of the gamma chain of human fibrinogen and is not involved in the fibrin polymerization reaction. Thromb. Res. 1983 Jan 1/15/1983; 29(2): 249-55. PMID: 6302942, PII: 0049-3848(83)90147-0, ISSN: 0049-3848.

Graber SE, Hawiger J. Evidence that changes in platelet cyclic AMP levels regulate the fibrinogen receptor on human platelets. J. Biol. Chem. 1982 Dec 12/25/1982; 257(24): 14606-9. PMID: 6294072, ISSN: 0021-9258.

Kloczewiak M, Timmons S, Hawiger J. Localization of a site interacting with human platelet receptor on carboxy-terminal segment of human fibrinogen gamma chain. Biochem. Biophys. Res. Commun. 1982 Jul 7/16/1982; 107(1): 181-7. PMID: 6289817, PII: 0006-291X(82)91686-2, ISSN: 0006-291X.

Fujimoto T, Ohara S, Hawiger J. Thrombin-induced exposure and prostacyclin inhibition of the receptor for factor VIII/von Willebrand factor on human platelets. J. Clin. Invest. 1982 Jun; 69(6): 1212-22. PMID: 6282932, PMCID: PMC370193, ISSN: 0021-9738.

Fujimoto T, Hawiger J. Adenosine diphosphate induces binding of von Willebrand factor to human platelets. Nature. 1982 May 5/13/1982; 297(5862): 154-6. PMID: 6281653, ISSN: 0028-0836.

Strong DD, Laudano AP, Hawiger J, Doolittle RF. Isolation, characterization, and synthesis of peptides from human fibrinogen that block the staphylococcal clumping reaction and construction of a synthetic clumping particle. Biochemistry. 1982 Mar 3/16/1982; 21(6): 1414-20. PMID: 7074096, ISSN: 0006-2960.

Hawiger J, Timmons S, Strong DD, Cottrell BA, Riley M, Doolittle RF. Identification of a region of human fibrinogen interacting with staphylococcal clumping factor. Biochemistry. 1982 Mar 3/16/1982; 21(6): 1407-13. PMID: 7074095, ISSN: 0006-2960.

Hawiger J, Timmons S, Kloczewiak M, Strong DD, Doolittle RF. Gamma and alpha chains of human fibrinogen possess sites reactive with human platelet receptors. Proc. Natl. Acad. Sci. U.S.A. 1982 Mar; 79(6): 2068-71. PMID: 6281794, PMCID: PMC346124, ISSN: 0027-8424.

Robertson RM, Robertson D, Friesinger GC, Timmons S, Hawiger J. Platelet aggregates in peripheral and coronary-sinus blood in patients with spontaneous coronary-artery spasm. Lancet. 1980 Oct 10/18/1980; 2(8199): 829-31. PMID: 6107502, ISSN: 0140-6736.

Schwartz MB, Hawiger J, Timmons S, Friesinger GC. Platelet aggregates in ischemic heart disease. Thromb. Haemost. 1980 Jul 7/15/1980; 43(3): 185-8. PMID: 7455982, ISSN: 0340-6245.

Des Prez RM, Steckley S, Stroud RM, Hawiger J. Interaction of Histoplasma capsulatum with human platelets. J. Infect. Dis. 1980 Jul; 142(1): 32-9. PMID: 7400626, ISSN: 0022-1899.

Hawiger J, Parkinson S, Timmons S. Prostacyclin inhibits mobilisation of fibrinogen-binding sites on human ADP- and thrombin-treated platelets. Nature. 1980 Jan 1/10/1980; 283(5743): 195-7. PMID: 6985716, ISSN: 0028-0836.

Hawiger J, Steckley S, Hammond D, Cheng C, Timmons S, Glick AD, Des Prez RM. Staphylococci-induced human platelet injury mediated by protein A and immunoglobulin G Fc fragment receptor. J. Clin. Invest. 1979 Oct; 64(4): 931-7. PMID: 479376, PMCID: PMC372201, DOI: 10.1172/JCI109559, ISSN: 0021-9738.

Cheng CM, Hawiger J. Affinity isolation and characterization of immunoglobulin G Fc fragment-binding glycoprotein from human blood platelets. J. Biol. Chem. 1979 Apr 4/10/1979; 254(7): 2165-7. PMID: 429275, ISSN: 0021-9258.

Hawiger J, Hammond DK, Timmons S, Budzynski AZ. Interaction of human fibrinogen with staphylococci: presence of a binding region on normal and abnormal fibrinogen variants and fibrinogen derivatives. Blood. 1978 May; 51(5): 799-812. PMID: 25098, ISSN: 0006-4971.

Timmons S, Hawiger J. Separation of human platelets from plasma proteins including factor VIII VWF by a combined albumin gradient-gel filtration method using HEPES buffer. Thromb. Res. 1978 Feb; 12(2): 297-306. PMID: 635845, PII: 0049-3848(78)90300-6, ISSN: 0049-3848.

Hawiger J, Hawiger A, Steckley S, Timmons S, Cheng C. Membrane changes in human platelets induced by lipopolysaccharide endotoxin. Br. J. Haematol. 1977 Feb; 35(2): 285-99. PMID: 322697, ISSN: 0007-1048.

Niewiarowski S, Lowery CT, Hawiger J, Millman M, Timmons S. Immunoassay of human platelet factor 4(PF4, antiheparin factor) by radial immunodiffusion. J. Lab. Clin. Med. 1976 Apr; 87(4): 720-33. PMID: 818325, PII: 0022-2143(76)90445-5, ISSN: 0022-2143.

Hawiger J. Disseminated intravascular coagulation in patients with infections: diagnostic and therapeutic approach. Mater Med Pol. 1976 Apr; 8(2): 206-12. PMID: 790030, ISSN: 0025-5246.

Hawiger J, Hammond DK, Timmons S. Human fibrinogen possesses binding site for staphyococci on Aalpha and Bbeta polypeptide chains. Nature. 1975 Dec 12/18/1975; 258(5536): 643-5. PMID: 1207746, ISSN: 0028-0836.

Hawiger A, Hawiger J, Timmons S, Steckley S, Cheng C. Proceedings: The role of membrane receptors in pathways of human platelet activation by endotoxin and other microbial products. Thromb Diath Haemorrh. 1975 Nov 11/15/1975; 34(2): 594. PMID: 1198508, ISSN: 0340-5338.

Hawiger J, Hammond DK, Timmons S. Proceedings: Pathobiology of human fibrinogen. Binding site for staphylococci on Aalpha and Bbeta chains of fibrinogen molecule. Thromb Diath Haemorrh. 1975 Sep 9/30/1975; 34(1): 324-5. PMID: 1188738, ISSN: 0340-5338.

Hawiger J, Hawiger A, Timmons S. Endotoxin-sensitive membrane component of human platelets. Nature. 1975 Jul 7/10/1975; 256(5513): 125-7. PMID: 1097934, ISSN: 0028-0836.

Des Prez RM, Bryan CS, Hawiger J, Colley DG. Function of the classical and alternate pathways of human complement in serum treated with ethylene glycol tetraacetic acid and MgCl2-ethylene glycol tetraacetic acid. Infect. Immun. 1975 Jun; 11(6): 1235-43. PMID: 806523, PMCID: PMC415205, ISSN: 0019-9567.

Hawiger J, Timmons S. Dynamic changes in the membrane of leukocyte lysosomes detected with fluorescent probe and accompanied by release of lysosomal enzymes. Biochem. Biophys. Res. Commun. 1973 Dec 12/19/1973; 55(4): 1278-84. PMID: 4771997, ISSN: 0006-291X.

Graybill JR, Hawiger J, Des Prez RM. Complement and coagulation in Rocky Mountain spotted fever. South. Med. J. 1973 Apr; 66(4): 410-3. PMID: 4708236, ISSN: 0038-4348.

Satterwhite TK, Hawiger J, Burklow SL, Koenig MG. Degradation products of fibrinogen and fibrin in bacteremia due to gram-negative rods. J. Infect. Dis. 1973 Apr; 127(4): 437-41. PMID: 4694546, ISSN: 0022-1899.

Hawiger J, Marney SR, Colley DG, Des Prez RM. Complement-dependent platelet injury by staphylococcal protein A. J. Exp. Med. 1972 Jul 7/1/1972; 136(1): 68-80. PMID: 4624450, PMCID: PMC2139193, ISSN: 0022-1007.

Hawiger J, Hawiger A, Koenig MG. Activation of lysosomal enzymes in polymorphonuclear leukocytic granules: the role of phospholipid-protein interaction. Yale J Biol Med. 1972 Feb; 45(1): 42-8. PMID: 5062739, PMCID: PMC2591777, ISSN: 0044-0086.

Hawiger J, Hawiger A, Koenig MG. Staphylococcal clumping and fibrinogen and fibrin degradation products in inflammatory exudate. Proc. Soc. Exp. Biol. Med. 1971 Jan; 136(1): 132-6. PMID: 4993215, ISSN: 0037-9727.

Hawiger J, Niewiarowski S, Gurewich V, Thomas DP. Measurement of fibrinogen and fibrin degradation products in serum by staphylococcal clumping test. J. Lab. Clin. Med. 1970 Jan; 75(1): 93-108. PMID: 4243578, PII: 0022-2143(70)90142-3, ISSN: 0022-2143.

Horn RG, Hawiger J, Collins RD. Electron microscopy of fibrin-like precipitate formed during the paracoagulation reaction between soluble fibrin monomer complexes and protamine sulphate. Br. J. Haematol. 1969 Nov; 17(5): 463-6. PMID: 5346822, ISSN: 0007-1048.

Hawiger J, Horn RG, Koenig MG, Collins RD. Activation and release of lysosomal enzymes from isolated leukocytic granules by liposomes. A proposed model for degranulation in polymorphonuclear leukocytes. Yale J Biol Med. 1969 Oct; 42(2): 57-70. PMID: 4317515, PMCID: PMC2591583, ISSN: 0044-0086.

Bóbr J, Hawiger J, Janus S, Sznapka L, Kalita S. [Intradepartmental infection in a children's clinic]. Pol Tyg Lek. 1969 Sep 9/23/1969; 24(38): 1452-5. PMID: 5349487, ISSN: 0032-3756.

Hawiger J, Collins RD, Horn RG. Precipitation of soluble fibrin monomer complexes by lysosomal protein fraction of polymorphonuclear leukocytes. Proc. Soc. Exp. Biol. Med. 1969 Jun; 131(2): 349-53. PMID: 5787109, ISSN: 0037-9727.

Hawiger J, Collins RD, Horn RG, Koenig MG. Interaction of artificial phospholipid membranes with isolated polymorphonuclear leucocytic granules. Nature. 1969 Apr 4/19/1969; 222(5190): 276-8. PMID: 5778395, ISSN: 0028-0836.

Zak C, Hawiger J, Jeljaszewicz J. [Susceptibility of Staphylococcus aureus to the effect of 30 antibiotics in vitro]. Przegl Epidemiol. 1969; 23(2): 279-92. PMID: 5803036, ISSN: 0033-2100.

Zak C, Hawiger J, Jeljaszewicz J. Sensitivity of Staphylococcus aureus to 30 antibiotics. Chemotherapy. 1969; 14(1): 7-21. PMID: 5772663, ISSN: 0009-3157.

Hawiger J. Frequency of staphylococcal lysozyme production tested by plate method. J. Clin. Pathol. 1968 May; 21(3): 390-3. PMID: 4880766, PMCID: PMC473803, ISSN: 0021-9746.

Hawiger J. [Synthesis and lysis of the cell wall of staphylococci]. Postepy Hig Med Dosw. 1968 Mar; 22(2): 223-61. PMID: 4874216, ISSN: 0032-5449.

Hawiger J. Purification and properties of lysozyme produced by Staphylococcus aureus. J. Bacteriol. 1968 Feb; 95(2): 376-84. PMID: 4966544, PMCID: PMC252029, ISSN: 0021-9193.

Hawiger J. [Staphylococcal lysozyme. 3. Factors influencing the course of reaction of staphylococcal lysozyme]. Med Dosw Mikrobiol. 1968; 20(2): 109-18. PMID: 4970247, ISSN: 0025-8601.

Hawiger J. [Staphylococcal lysozyme. 4. Lysozyme activity towards various substrates]. Med Dosw Mikrobiol. 1968; 20(2): 119-24. PMID: 4876193, ISSN: 0025-8601.

Hawiger J. [Staphylococcal lysozyme. II. Purification of lysozyme produced by Staphylococcus aureus 524]. Med Dosw Mikrobiol. 1968; 20(1): 1-7. PMID: 4874194, ISSN: 0025-8601.

Lipinski B, Hawiger J, Jeljaszewicz J. Staphylococcal clumping with soluble fibrin mmonomer complexes. J. Exp. Med. 1967 Nov 11/1/1967; 126(5): 979-88. PMID: 4228857, PMCID: PMC2138412, ISSN: 0022-1007.