Mario Gonzalez-Gronow | Scholars@Duke

Mario Gonzalez-Gronow
Associate Professor Emeritus of Pathology

I am primarily involved in studies of the regulation of the plasminogen (Pg) activation system in rheumatoid human synovial fibroblasts relative to endothelial cells, hepatocytes and monocytes. We have found that streptococcal antigens like streptokinase (SK) are able to mimic binding properties of human fibronectin (FN) and thereby have the potential to affect processes on the cell surface involving FN interaction with their normal receptors. Rheumatoid arthritis (RA) in humans is a disease characterized by a chronic autoimmune related inflammatory process focused in the joints leading to a vast destruction of synovial tissue and bone. We have found a correlation between the stage of the disease and the titer of anti-SK antibodies cross-reacting with FN. In addition, we also found that the Pg receptor in RA human synovial fibroblasts has a composition different from that found in normal synovial fibroblasts. We identified the protein components of both normal and RA synovial fibroblasts. These findings led us to postulate a new mechanism which explains the molecular basis for the upregulation of Pg activity on the surface of the rheumatoid inflammed synovium. I am also involved in the study of Pg receptors in prostate cancer cells. I found that the voltage-dependent anion channel (VDAC1) along with the chaperone protein glucose-regulated protein of 78 kDa serve as receptors for Pg. Furthermore, we identified the binding site for alpha-2-macroglobulin in GRP78. This site is the target of autoimmunity in prostate cancer patients who show elevated titers of anti-GRP78 autoantibodies which stimulate tumor cell proliferation. We are presently studying the mechanism by which these autoantibodies protect the tumor cells from apoptosis.

Current Appointments & Affiliations

Associate Professor Emeritus of Pathology, Pathology, Clinical Science Departments 2011

Contact Information

304 Davison Bldg, Durham, NC 27710
Duke Box 3712, Durham, NC 27710
gonza002@mc.duke.edu (919) 684-8879

Background
Education, Training, & Certifications
- D.Sc., University of Chile 1973
- B.S., University of Concepcion (Chile) 1969
Duke Appointment History
- Associate Professor of Pathology, Pathology, Clinical Science Departments 2006 - 2011
- Associate Research Professor of Pathology, Pathology, Clinical Science Departments 2005 - 2006
- Assistant Research Professor of Pathology, Pathology, Clinical Science Departments 1994 - 2005
Research
Selected Grants
- Modulation of Angiogenesis Via the Angiostatin Receptor awarded by National Institutes of Health 2001 - 2007
- Fibrinolysis In Vitro And In Vivo awarded by National Institutes of Health 1995
- Lipoprotein (A), Coagulation And Fibrinolysis awarded by National Institutes of Health 1993 - 1994
- Biosynthesis And Secretion Of Plasminogen awarded by National Institutes of Health 1985 - 1986
Publications & Artistic Works
Selected Publications
- Conference Papers
  - Al-Hashimi, A, Shayegan, B, Majeed, F, Lebeau, PF, Hoogenes, J, Polena, E, Gonzalez-Gronow, M, Pizzo, S, and Austin, RC. "Contribution of Anti-GRP78 autoantibodies to prostate cancer progression through tissue factor procoagulant activity." April 2015. Link to Item
  - Gonzalez-Gronow, M, Kaczowka, S, Payne, S, Wang, F, Gawdi, G, and Pizzo, S. "Plasminogen structural domains exhibit different functions when associated with cell surface GRP78 or VDAC." July 2007. Link to Item
- Journal Articles
  - Gonzalez-Gronow, M, Fiedler, JL, Farias Gomez, C, Wang, F, Ray, R, Ferrell, PD, and Pizzo, SV. "Myelin basic protein stimulates plasminogen activation via tissue plasminogen activator following binding to independent l-lysine-containing domains." Biochemical and biophysical research communications 490, no. 3 (August 2017): 855-860. Full Text
  - Al-Hashimi, AA, Caldwell, J, Gonzalez-Gronow, M, Pizzo, SV, Aboumrad, D, Pozza, L, Al-Bayati, H, Weitz, JI, Stafford, A, Chan, H, Kapoor, A, Jacobsen, DW, Dickhout, JG, and Austin, RC. "Binding of anti-GRP78 autoantibodies to cell surface GRP78 increases tissue factor procoagulant activity via the release of calcium from endoplasmic reticulum stores." The Journal of biological chemistry 290, no. 48 (November 2015): 28725-. Full Text
  - Gonzalez-Gronow, M, Cuchacovich, M, Francos, R, Cuchacovich, S, Blanco, A, Sandoval, R, Gomez, CF, Valenzuela, JA, Ray, R, and Pizzo, SV. "Catalytic autoantibodies against myelin basic protein (MBP) isolated from serum of autistic children impair in vitro models of synaptic plasticity in rat hippocampus." Journal of neuroimmunology 287 (October 2015): 1-8. Full Text
  - Gonzalez-Gronow, M, Gomez, CF, de Ridder, GG, Ray, R, and Pizzo, SV. "Binding of tissue-type plasminogen activator to the glucose-regulated protein 78 (GRP78) modulates plasminogen activation and promotes human neuroblastoma cell proliferation in vitro." The Journal of Biological Chemistry 289, no. 36 (September 2014): 25166-25176. Full Text
  - Gonzalez-Gronow, M, Ray, R, Wang, F, and Pizzo, SV. "The voltage-dependent anion channel (VDAC) binds tissue-type plasminogen activator and promotes activation of plasminogen on the cell surface." The Journal of Biological Chemistry 288, no. 1 (January 2013): 498-509. Full Text
  - Selim, MA, Burchette, JL, Bowers, EV, de Ridder, GG, Mo, L, Pizzo, SV, and Gonzalez-Gronow, M. "Changes in oligosaccharide chains of autoantibodies to GRP78 expressed during progression of malignant melanoma stimulate melanoma cell growth and survival." Melanoma Research 21, no. 4 (August 2011): 323-334. Full Text
  - de Ridder, GG, Gonzalez-Gronow, M, Ray, R, and Pizzo, SV. "Autoantibodies against cell surface GRP78 promote tumor growth in a murine model of melanoma." Melanoma Research 21, no. 1 (February 2011): 35-43. Full Text
  - Gonzalez-Gronow, M, Cuchacovich, M, Francos, R, Cuchacovich, S, Fernandez, MDP, Blanco, A, Bowers, EV, Kaczowka, S, and Pizzo, SV. "Antibodies against the voltage-dependent anion channel (VDAC) and its protective ligand hexokinase-I in children with autism." Journal of Neuroimmunology 227, no. 1-2 (October 2010): 153-161. Full Text
  - Al-Hashimi, AA, Caldwell, J, Gonzalez-Gronow, M, Pizzo, SV, Aboumrad, D, Pozza, L, Al-Bayati, H, Weitz, JI, Stafford, A, Chan, H, Kapoor, A, Jacobsen, DW, Dickhout, JG, and Austin, RC. "Binding of anti-GRP78 autoantibodies to cell surface GRP78 increases tissue factor procoagulant activity via the release of calcium from endoplasmic reticulum stores." The Journal of Biological Chemistry 285, no. 37 (September 2010): 28912-28923. Full Text
  - Papalas, JA, Vollmer, RT, Gonzalez-Gronow, M, Pizzo, SV, Burchette, J, Youens, KE, Johnson, KB, and Selim, MA. "Patterns of GRP78 and MTJ1 expression in primary cutaneous malignant melanoma." Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc 23, no. 1 (January 2010): 134-143. Full Text
  - Gonzalez-Gronow, M, Selim, MA, Papalas, J, and Pizzo, SV. "GRP78: a multifunctional receptor on the cell surface." Antioxidants & Redox Signaling 11, no. 9 (September 2009): 2299-2306. (Review) Full Text
  - Gonzalez-Gronow, M, Kaczowka, S, Gawdi, G, and Pizzo, SV. "Dipeptidyl peptidase IV (DPP IV/CD26) is a cell-surface plasminogen receptor. (Published online)" Front Biosci 13 (January 1, 2008): 1610-1618. (Review) Link to Item
  - Papalas, J, Turner, J, Burchette, J, Gonzalez-Gronow, M, and Selim, M. "GRP 78 protein expression in malignant melanoma." JOURNAL OF CUTANEOUS PATHOLOGY 35, no. 1 (January 2008): 135-135. Link to Item
  - Gonzalez-Gronow, M, Kaczowka, SJ, Payne, S, Wang, F, Gawdi, G, and Pizzo, SV. "Plasminogen structural domains exhibit different functions when associated with cell surface GRP78 or the voltage-dependent anion channel." The Journal of Biological Chemistry 282, no. 45 (November 2007): 32811-32820. Full Text
  - Gonzalez-Gronow, M, Cuchacovich, M, Llanos, C, Urzua, C, Gawdi, G, and Pizzo, SV. "Prostate cancer cell proliferation in vitro is modulated by antibodies against glucose-regulated protein 78 isolated from patient serum." Cancer Res 66, no. 23 (December 1, 2006): 11424-11431. Full Text Link to Item
  - Mavropoulos, JC, Cuchacovich, M, Llanos, C, Aguillón, JC, Gatica, H, Pizzo, SV, and Gonzalez-Gronow, M. "Anti-tumor necrosis factor-alpha therapy augments dipeptidyl peptidase IV activity and decreases autoantibodies to GRP78/BIP and phosphoglucose isomerase in patients with rheumatoid arthritis." The Journal of Rheumatology 32, no. 11 (November 2005): 2116-2124.
  - Wahl, ML, Kenan, DJ, Gonzalez-Gronow, M, and Pizzo, SV. "Angiostatin's molecular mechanism: aspects of specificity and regulation elucidated." J Cell Biochem 96, no. 2 (October 1, 2005): 242-261. (Review) Full Text Link to Item
  - Cuchacovich, M, Merino, G, Yamamoto, JH, Villarroel, F, Saavedra, T, Jofre, S, Gatica, H, Velasquez, V, Pizzo, SV, and Gonzalez-Gronow, M. "Behçet's disease patients present high levels of deglycosylated anti-lipoteichoic acid IgG and high IL-8 production after lipoteichoic acid stimulation." Clin Exp Rheumatol 23, no. 4 Suppl 38 (July 2005): S27-S34. Link to Item
  - Gonzalez-Gronow, M, Misra, UK, Gawdi, G, and Pizzo, SV. "Association of plasminogen with dipeptidyl peptidase IV and Na+/H+ exchanger isoform NHE3 regulates invasion of human 1-LN prostate tumor cells." The Journal of Biological Chemistry 280, no. 29 (July 2005): 27173-27178. Full Text
  - Gonzalez-Gronow, M, Grenett, HE, Gawdi, G, and Pizzo, SV. "Angiostatin directly inhibits human prostate tumor cell invasion by blocking plasminogen binding to its cellular receptor, CD26." Exp Cell Res 303, no. 1 (February 1, 2005): 22-31. Full Text Link to Item
  - Misra, UK, Gonzalez-Gronow, M, Gawdi, G, and Pizzo, SV. "The role of MTJ-1 in cell surface translocation of GRP78, a receptor for alpha 2-macroglobulin-dependent signaling." Journal of Immunology (Baltimore, Md. : 1950) 174, no. 4 (February 2005): 2092-2097. Full Text
  - Misra, UK, Gonzalez-Gronow, M, Gawdi, G, Wang, F, and Pizzo, SV. "A novel receptor function for the heat shock protein Grp78: silencing of Grp78 gene expression attenuates alpha2M*-induced signalling." Cell Signal 16, no. 8 (August 2004): 929-938. Full Text Link to Item
  - Gonzalez-Gronow, M, Hershfield, MS, Arredondo-Vega, FX, and Pizzo, SV. "Cell surface adenosine deaminase binds and stimulates plasminogen activation on 1-LN human prostate cancer cells." The Journal of Biological Chemistry 279, no. 20 (May 2004): 20993-20998. Full Text
  - Gonzalez-Gronow, M, Kalfa, T, Johnson, CE, Gawdi, G, and Pizzo, SV. "The voltage-dependent anion channel is a receptor for plasminogen kringle 5 on human endothelial cells." J Biol Chem 278, no. 29 (July 18, 2003): 27312-27318. Full Text Link to Item
  - Cuchacovich, M, Gatica, H, Vial, P, Yovanovich, J, Pizzo, SV, and Gonzalez-Gronow, M. "Streptokinase promotes development of dipeptidyl peptidase IV (CD26) autoantibodies after fibrinolytic therapy in myocardial infarction patients." Clinical and Diagnostic Laboratory Immunology 9, no. 6 (November 2002): 1253-1259. Full Text
  - Misra, UK, Gonzalez-Gronow, M, Gawdi, G, Hart, JP, Johnson, CE, and Pizzo, SV. "The role of Grp 78 in alpha 2-macroglobulin-induced signal transduction. Evidence from RNA interference that the low density lipoprotein receptor-related protein is associated with, but not necessary for, GRP 78-mediated signal transduction." The Journal of Biological Chemistry 277, no. 44 (November 2002): 42082-42087. Full Text
  - Gonzalez-Gronow, M, Gawdi, G, and Pizzo, SV. "Tissue factor is the receptor for plasminogen type 1 on 1-LN human prostate cancer cells." Blood 99, no. 12 (June 2002): 4562-4567. Full Text
  - Cuchacovich, M, Gatica, H, Pizzo, SV, and Gonzalez-Gronow, M. "Characterization of human serum dipeptidyl peptidase IV (CD26) and analysis of its autoantibodies in patients with rheumatoid arthritis and other autoimmune diseases." Clinical and Experimental Rheumatology 19, no. 6 (November 2001): 673-680.
  - Gonzalez-Gronow, M, Grenett, HE, Weber, MR, Gawdi, G, and Pizzo, SV. "Interaction of plasminogen with dipeptidyl peptidase IV initiates a signal transduction mechanism which regulates expression of matrix metalloproteinase-9 by prostate cancer cells." Biochem J 355, no. Pt 2 (April 15, 2001): 397-407. Link to Item
  - Asplin, IR, Misra, UK, Gawdi, G, Gonzalez-Gronow, M, and Pizzo, SV. "Selective upregulated expression of the alpha2-macroglobulin signaling receptor in highly metastatic 1-LN prostate carcinoma cells." Arch Biochem Biophys 383, no. 1 (November 1, 2000): 135-141. Full Text Link to Item
  - Misra, UK, Gawdi, G, Gonzalez-Gronow, M, and Pizzo, SV. "Coordinate regulation of the alpha(2)-macroglobulin signaling receptor and the low density lipoprotein receptor-related protein/alpha(2)-macroglobulin receptor by insulin." J Biol Chem 274, no. 36 (September 3, 1999): 25785-25791. Link to Item
  - Shearin, TV, Pizzo, SV, and Gonzalez-Gronow, M. "Molecular abnormalities of human plasminogen isolated from synovial fluid of rheumatoid arthritis patients." J Mol Med (Berl) 75, no. 5 (May 1997): 378-385. Link to Item
  - Misra, UK, Gonzalez-Gronow, M, Gawdi, G, and Pizzo, SV. "Up-regulation of the alpha2-macroglobulin signaling receptor on rheumatoid synovial fibroblasts." J Biol Chem 272, no. 1 (January 3, 1997): 497-502. Link to Item
  - Gonzalez-Gronow, M, Cuchacovich, M, Grigg, DM, and Pizzo, SV. "Analysis of autoantibodies to plasminogen in the serum of patients with rheumatoid arthritis." Journal of Molecular Medicine (Berlin, Germany) 74, no. 8 (August 1996): 463-469. Full Text
  - Cuchacovich, M, Gatica, H, Grigg, DM, Pizzo, SV, and Gonzalez-Gronow, M. "Potential pathogenicity of deglycosylated IgG cross reactive with streptokinase and fibronectin in the serum of patients with rheumatoid arthritis." J Rheumatol 23, no. 1 (January 1996): 44-51. Link to Item
  - Serrano, RL, Rodriguez, P, Pizzo, SV, and Gonzalez-Gronow, M. "ATP-regulated activity of the plasmin-streptokinase complex: a novel mechanism involving phosphorylation of streptokinase." Biochem J 313 ( Pt 1) (January 1, 1996): 171-177. Link to Item
  - Gonzalez-Gronow, M, Gawdi, G, and Pizzo, SV. "Characterization of the plasminogen receptors of normal and rheumatoid arthritis human synovial fibroblasts." J Biol Chem 269, no. 6 (February 11, 1994): 4360-4366. Link to Item
  - Gonzalez-Gronow, M, Gawdi, G, and Pizzo, SV. "Plasminogen activation stimulates an increase in intracellular calcium in human synovial fibroblasts." J Biol Chem 268, no. 28 (October 5, 1993): 20791-20795. Link to Item
  - Gonzalez-Gronow, M, Enghild, JJ, and Pizzo, SV. "Streptokinase and human fibronectin share a common epitope: implications for regulation of fibrinolysis and rheumatoid arthritis." Biochim Biophys Acta 1180, no. 3 (January 22, 1993): 283-288. Link to Item
  - Stack, MS, Pizzo, SV, and Gonzalez-Gronow, M. "Effect of desialylation on the biological properties of human plasminogen." Biochem J 284 ( Pt 1) (May 15, 1992): 81-86. Link to Item
  - Gonzalez-Gronow, M, Stack, S, and Pizzo, SV. "Plasmin binding to the plasminogen receptor enhances catalytic efficiency and activates the receptor for subsequent ligand binding." Arch Biochem Biophys 286, no. 2 (May 1, 1991): 625-628. Link to Item
  - Stack, S, Gonzalez-Gronow, M, and Pizzo, SV. "The effect of divalent cations on the conformation and function of human plasminogen." Arch Biochem Biophys 284, no. 1 (January 1991): 58-62. Link to Item
  - Gonzalez-Gronow, M, Grenett, HE, Fuller, GM, and Pizzo, SV. "The role of carbohydrate in the function of human plasminogen: comparison of the protein obtained from molecular cloning and expression in Escherichia coli and COS cells." Biochim Biophys Acta 1039, no. 3 (July 6, 1990): 269-276. Link to Item
  - Edelberg, JM, Enghild, JJ, Pizzo, SV, and Gonzalez-Gronow, M. "Neonatal plasminogen displays altered cell surface binding and activation kinetics. Correlation with increased glycosylation of the protein." J Clin Invest 86, no. 1 (July 1990): 107-112. Full Text Link to Item
  - Stack, S, Gonzalez-Gronow, M, and Pizzo, SV. "Regulation of plasminogen activation by components of the extracellular matrix." Biochemistry 29, no. 20 (May 22, 1990): 4966-4970. Link to Item
  - Edelberg, JM, Gonzalez-Gronow, M, and Pizzo, SV. "Lipoprotein(a) inhibition of plasminogen activation by tissue-type plasminogen activator." Thromb Res 57, no. 1 (January 1, 1990): 155-162. Link to Item
  - Edelberg, JM, Gonzalez-Gronow, M, and Pizzo, SV. "Lipoprotein a inhibits streptokinase-mediated activation of human plasminogen." Biochemistry 28, no. 6 (March 21, 1989): 2370-2374. Link to Item
  - Gonzalez-Gronow, M, Edelberg, JM, and Pizzo, SV. "Further characterization of the cellular plasminogen binding site: evidence that plasminogen 2 and lipoprotein a compete for the same site." Biochemistry 28, no. 6 (March 21, 1989): 2374-2377. Link to Item
  - Gonzalez-Gronow, M, and Robbins, KC. "In vitro biosynthesis of plasminogen in a cell-free system directed by mRNA fractions isolated from monkey liver." Biochemistry 23, no. 2 (January 17, 1984): 190-196. Link to Item
  - Gonzalez-Gronow, M, Siefring, GE, and Castellino, FJ. "Mechanism of activation of human plasminogen by the activator complex, streptokinase-plasmin." J Biol Chem 253, no. 4 (February 25, 1978): 1090-1094. Link to Item
  - Gonzalez-Gronow, M, Violand, BN, and Castellino, FJ. "Purification and some properties of the Glu- and Lys-human plasmin heavy chains." J Biol Chem 252, no. 7 (April 10, 1977): 2175-2177. Link to Item

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Education, Training, & Certifications

Duke Appointment History

Selected Grants

Selected Publications

Conference Papers

Journal Articles