Charles S. Greenberg, MD

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Services

• Hematology

Department / Division:
Medicine / Hematology

Address:
DUMC 2603
Durham, NC 27710

Appointment Telephone:
919-684-6464

Office Telephone:
919-684-6703

Fax Telephone:
919-684-6824

• MD, Drexel University School of Medicine, Pennsylvania, 1976

• Medicine, University of Minnesota

• Hematology-Oncology, University of California at San Francisco

Clinical Interests:
General Hematology, Sickle cell disease, Clinical disorders of Hemostasis and thrombosis, Platelet disorders

Research Interests:
My research laboratory is studying the structure and function of the enzymes called transglutaminases that are responsible for stabilizing tissues. Our laboratory is expressing Factor XlIIa and analyzing the effects of site- directed mutagenesis and deletion analysis on Factor XIIIa function. Information derived from these studies will have an impact on treating thrombotic and hemostatic diseases.

In addition, this laboratory is investigating the enzyme expressed in endothelial and smooth muscle cells called tissue transglutarninase. The enzymatic activity of the tissue transglutaminase is stimulated by calcium ions and inhibited by GTP and ATP. The localization of the GTP/ATP binding sites, substrate binding sites and identification of the intra- extracellular substrates is being analyzed using recombinant DNA methods. These results should define the role of this enzyme in normal vascular function and atherosclerotic disorders.

2/2198 10:2') AM
(fibrinolysis , vascular biology, protein engineering, molecular biology)

Representative Publications:
Sane DC, Kontos JL, Greenberg CS. Roles of transglutaminases in cardiac and vascular diseases. Front Biosci. 2007;12:2530-45. (2007) Abstract

Sane DC, Kontos JL, Greenberg CS. Roles of transglutaminases in cardiac and vascular diseases. Front Biosci. 2007;12:2530-45. (2007) Abstract

Parsons AC, Yosipovitch G, Sheehan DJ, Sangüeza OP, Greenberg CS, Sane DC. Transglutaminases: the missing link in nephrogenic systemic fibrosis. Am J Dermatopathol. 2007 Oct;29(5):433-6. (2007) Abstract

Parsons AC, Yosipovitch G, Sheehan DJ, Sangüeza OP, Greenberg CS, Sane DC. Transglutaminases: the missing link in nephrogenic systemic fibrosis. Am J Dermatopathol. 2007 Oct;29(5):433-6. (2007) Abstract

Lai TS, Liu Y, Li W, Greenberg CS. Identification of two GTP-independent alternatively spliced forms of tissue transglutaminase in human leukocytes, vascular smooth muscle, and endothelial cells. FASEB J. 2007 Jul 3. (2007) Abstract

Lai TS, Liu Y, Li W, Greenberg CS. Identification of two GTP-independent alternatively spliced forms of tissue transglutaminase in human leukocytes, vascular smooth muscle, and endothelial cells. FASEB J. 2007 Jul 3. (2007) Abstract

Gupta M, Greenberg CS, Eckman DM, Sane DC. Arterial vimentin is a transglutaminase substrate: a link between vasomotor activity and remodeling?  J Vasc Res.  2007;44(5):339-44. (2007) Abstract

Gupta M, Greenberg CS, Eckman DM, Sane DC. Arterial vimentin is a transglutaminase substrate: a link between vasomotor activity and remodeling? J Vasc Res. 2007;44(5):339-44. (2007) Abstract

Mazooz G, Mehlman T, Lai TS, Greenberg CS, Dewhirst MW, Neeman M. Development of magnetic resonance imaging contrast material for in vivo mapping of tissue transglutaminase activity. Cancer Res. 2005 Feb 15;65(4):1369-75. (2005) Abstract

Mazooz G, Mehlman T, Lai TS, Greenberg CS, Dewhirst MW, Neeman M. Development of magnetic resonance imaging contrast material for in vivo mapping of tissue transglutaminase activity. Cancer Res. 2005 Feb 15;65(4):1369-75. (2005) Abstract

Bennett-Guerrero E, Slaughter TF, White WD, Welsby IJ, Greenberg CS, El-Moalem H, Ortel TL. Preoperative anti-PF4/heparin antibody level predicts adverse outcome after cardiac surgery. J Thorac Cardiovasc Surg. 2005 Dec;130(6):1567-72. (2005) Abstract

Bennett-Guerrero E, Slaughter TF, White WD, Welsby IJ, Greenberg CS, El-Moalem H, Ortel TL. Preoperative anti-PF4/heparin antibody level predicts adverse outcome after cardiac surgery. J Thorac Cardiovasc Surg. 2005 Dec;130(6):1567-72. (2005) Abstract

Lai TS, Tucker T, Burke JR, Strittmatter WJ, Greenberg CS. Effect of tissue transglutaminase on the solubility of proteins containing expanded polyglutamine repeats. J Neurochem. 2004 Mar;88(5):1253-60. (2004) Abstract

Lai TS, Tucker T, Burke JR, Strittmatter WJ, Greenberg CS. Effect of tissue transglutaminase on the solubility of proteins containing expanded polyglutamine repeats. J Neurochem. 2004 Mar;88(5):1253-60. (2004) Abstract

Summey BT Jr, Graff RD, Lai TS, Greenberg CS, Lee GM. Tissue transglutaminase localization and activity regulation in the extracellular matrix of articular cartilage. J Orthop Res. 2002 Jan;20(1):76-82. (2002) Abstract

Haroon ZA, Amin K, Saito W, Wilson W, Greenberg CS, Dewhirst MW. SU5416 delays wound healing through inhibition of TGF-beta 1 activation. Cancer Biol Ther. 2002 Mar-Apr;1(2):121-6. (2002) Abstract

Ariëns RA, Lai TS, Weisel JW, Greenberg CS, Grant PJ. Role of factor XIII in fibrin clot formation and effects of genetic polymorphisms. Blood. 2002 Aug 1;100(3):743-54. (2002) Abstract

Ariëns RA, Lai TS, Weisel JW, Greenberg CS, Grant PJ. Role of factor XIII in fibrin clot formation and effects of genetic polymorphisms. Blood. 2002 Aug 1;100(3):743-54. (2002) Abstract

Slaughter TF, Sreeram G, Sharma AD, El-Moalem H, East CJ, Greenberg CS. Reversible shear-mediated platelet dysfunction during cardiac surgery as assessed by the PFA-100 platelet function analyzer. Blood Coagul Fibrinolysis. 2001 Mar;12(2):85-93. (2001) Abstract

Slaughter TF, Mark JB, El-Moalem H, Hayward KA, Hilton AK, Hodgins LP, Greenberg CS. Hemostatic effects of antithrombin III supplementation during cardiac surgery: results of a prospective randomized investigation. Blood Coagul Fibrinolysis. 2001 Jan;12(1):25-31. (2001) Abstract

Lai TS, Hausladen A, Slaughter TF, Eu JP, Stamler JS, Greenberg CS. Calcium regulates S-nitrosylation, denitrosylation, and activity of tissue transglutaminase. Biochemistry. 2001 Apr 24;40(16):4904-10. (2001) Abstract

Haroon ZA, Wannenburg T, Gupta M, Greenberg CS, Wallin R, Sane DC. Localization of tissue transglutaminase in human carotid and coronary artery atherosclerosis: implications for plaque stability and progression. Lab Invest. 2001 Jan;81(1):83-93. (2001) Abstract

Ortel TL, James AH, Thames EH, Moore KD, Greenberg CS. Assessment of primary hemostasis by PFA-100 analysis in a tertiary care center. Thromb Haemost. 2000 Jul;84(1):93-7. (2000) Abstract

Lubarsky DA, Fisher SD, Slaughter TF, Green CL, Lineberger CK, Astles JR, Greenberg CS, Inge WW 3rd, Krucoff MW. Myocardial ischemia correlates with reduced fibrinolytic activity following peripheral vascular surgery. J Clin Anesth. 2000 Mar;12(2):136-41. (2000) Abstract

Haroon ZA, Raleigh JA, Greenberg CS, Dewhirst MW. Early wound healing exhibits cytokine surge without evidence of hypoxia. Ann Surg. 2000 Jan;231(1):137-47. (2000) Abstract

Franck LS, Greenberg CS, Stevens B. Pain assessment in infants and children. Pediatr Clin North Am. 2000 Jun;47(3):487-512. (2000) Abstract

Blackwell KL, Haroon ZA, Shan S, Saito W, Broadwater G, Greenberg CS, Dewhirst MW. Tamoxifen inhibits angiogenesis in estrogen receptor-negative animal models. Clin Cancer Res. 2000 Nov;6(11):4359-64. (2000) Abstract

Haroon ZA, Lai TS, Hettasch JM, Lindberg RA, Dewhirst MW, Greenberg CS. Tissue transglutaminase is expressed as a host response to tumor invasion and inhibits tumor growth. Lab Invest. 1999 Dec;79(12):1679-86. (1999) Abstract

Haroon ZA, Hettasch JM, Lai TS, Dewhirst MW, Greenberg CS. Tissue transglutaminase is expressed, active, and directly involved in rat dermal wound healing and angiogenesis. FASEB J. 1999 Oct;13(13):1787-95. (1999) Abstract

T-S Lai, T. F. Slaughter, K. A. Peoples, J. M. Hettasch, and C. S. Greenberg . "Regulation of Human Tissue Transglutaminase Function By Magnesium-Nucleotide Complexes: Identification of Distinct Binding Sites for Mg-GTP and Mg-ATP," J. Biological Chemistry. 273 : 1776-1781, 1998. (1998)

M. L. Hursting, T. F. Slaughter, A. G. Stead, K. M. Szewczyk, D. J. Witt, and C. S. Greenberg. "Standardization of Prothrombin Fragment 1.2 Measurement," Arch. Pathol. Lab. Med. V122, 1998. (1998)

J. P. Zidar, K. R. Kruse, S. D. Berkowitz, C. S. Greenberg, J. B. Muhlestein, J. Eff, M. W. Krucoff, L. H. Gardner, and R. M. Califf. "Enoxaparin and TIClopidine after Elective Stenting: The ENTICES Trial," Submitted to Circulation. (1998)

T.F. Slaughter, F. Faghih, C.S. Greenberg, J.B. Leslie, and R.N. Sladen. "The Effects ofe-Aminocaproic Acid on Fibrinolysis and Thrombin Generation During Cardiac Surgery," Cardiovascular Anesthesia, 85:1221-6, 1997. (1997)

T.F. Slaughter and C.S. Greenberg. "Heparin-associated Thrombocytopenia and Thrombosis," Anesthesiology, 87: 667-675, September, 1997. (1997)

T.F. Slaughter and C.S. Greenberg. "Antifibrinolytic Drugs and Perioperative Hemostasis," American J. of Hematology, 56:32-36, 1997 (1997)

A. L. Wong, Z. A. Haroon, S. Werner, M. W. Dewhirst, C. S. Greenberg, and K. G. Peters. "Tie2 Expression and Phosphorylation in Angiogenic and Quiescent Adult Tissues," Circulation Research. V81, No 4, Oct. 1997. T-S Lai, T. F. Slaughter, K. A. Peoples, J. M. Hettasch, and C. S. Greenberg . "Regulation of Human Tissue Transglutaminase Function By Magnesium-Nucleotide Complexes: Identification of Distinct Binding Sites for Mg-GTP and Mg-ATP," J. Biological Chemistry. 273 : 1776-1781, 1998. (1997)

T-S Lai, T. F. Slaughter, C. M. Koropchak, Z. A. Haroon, and C. S. Greenberg. "C-terminal Deletion of Human Tissue Transglutaminase Enhances Magnesium-dependent GTP/ATPase Activity," J. Biological Chemistry. 271 : 31191 - 195, 1996. T.F. Slaughter, C.S. Greenberg, "Practice Guidelines and Treatment of Patients with von willebrand's Disease," Anesthesiology, V 85, No2, Aug. 1996. (1996)

T-S Lai, T. F. Slaughter, C. M. Koropchak, Z. A. Haroon, and C. S. Greenberg. "C-terminal Deletion of Human Tissue Transglutaminase Enhances Magnesium-dependent GTP/ATPase Activity," J. Biological Chemistry. 271 : 31191 - 195, 1996. T-S Lai, Alicja Bielawska, K.A. Peoples, Y. A. Hannun and C. S. Greenberg. "Sphingosylphosphocholine Reduces the Calcium Ion Requirement for Activating Tissue Transglutaminase," J. Biological Chemistry. 1997. (1996)

J.M. Hettasch, N. Bandarenko, T-S Lai, J. Marks, Z. Haroon, K. Peters, M. Dewhirst, D. Iglehart, C.S. Greenberg. "Tissue Transglutaminase Expression in Human Breast Cancer," Laboratory Investigation 75: 1-9, 1996. (1996)

J.M. Hettasch, N. Bandarenko, T-S Lai, J. Marks, Z. Haroon, K. Peters, M. Dewhirst, D. Iglehart, C.S. Greenberg. "Tissue Transglutaminase Expression in Human Breast Cancer," Laboratory Investigation 75: 1-9, 1996. (1996)