Scholars@Duke
Mario Gonzalez-Gronow

Mario Gonzalez-Gronow

Associate Professor Emeritus of Pathology
Pathology
gonza002@mc.duke.edu
Duke Box 3712, Durham, NC 27710
304 Davison Bldg, Durham, NC 27710

Overview

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 · 2011 - Present Pathology, Clinical Science Departments

Recent Publications

Physiological Roles of the Autoantibodies to the 78-Kilodalton Glucose-Regulated Protein (GRP78) in Cancer and Autoimmune Diseases.

Journal Article Biomedicines · May 24, 2022 The 78 kDa glucose-regulated protein (GRP78), a member of the 70 kDa heat-shock family of molecular chaperones (HSP70), is essential for the regulation of the unfolded protein response (UPR) resulting from cellular endoplasmic reticulum (ER) stress. During ... Full text Link to item Cite

Glucose-regulated protein (GRP78) is an important cell surface receptor for viral invasion, cancers, and neurological disorders.

Journal Article IUBMB life · June 2021 The 78 kDa glucose-regulated protein (GRP78) is an endoplasmic reticulum (ER)-resident molecular chaperone. GRP78 is a member of the 70 kDa heat shock family of proteins involved in correcting and clearing misfolded proteins in the ER. In response to cellu ... Full text Open Access Cite
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Recent Grants

Modulation of Angiogenesis Via the Angiostatin Receptor

ResearchCo Investigator · Awarded by National Institutes of Health · 2001 - 2007

Fibrinolysis In Vitro And In Vivo

ResearchCo-Principal Investigator · Awarded by National Institutes of Health · 1995 - 1995

Lipoprotein (A), Coagulation And Fibrinolysis

ResearchCo-Principal Investigator · Awarded by National Institutes of Health · 1993 - 1994

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Education, Training & Certifications

University of Chile (Chile) · 1973 D.Sc.
University of Concepcion (Chile) · 1969 B.S.