Overview
RESEARCH ABSTRACT
Studies from this laboratory identified cell surface expression of the molecular chaperone GRP78 as a major factor in prostate cancer and other malignancies. Cell surface GRP78 functions as a signaling receptor promoting tumor proliferation and suppressing apoptosis. Patients with a number of malignancies mount an autoimmune response to GRP78 and these antibodies, which bind to the NH2 terminal domains of GRP78, are receptor agonists whose appearance is a marker of poor prognosis. More recently, we have shown that antibodies directed against the COOH-terminal domain of GRP78 are receptor antagonists which may have therapeutic potential for treating patients whose tumors express GRP78 on the cell surface.
Studies from this laboratory identified cell surface expression of the molecular chaperone GRP78 as a major factor in prostate cancer and other malignancies. Cell surface GRP78 functions as a signaling receptor promoting tumor proliferation and suppressing apoptosis. Patients with a number of malignancies mount an autoimmune response to GRP78 and these antibodies, which bind to the NH2 terminal domains of GRP78, are receptor agonists whose appearance is a marker of poor prognosis. More recently, we have shown that antibodies directed against the COOH-terminal domain of GRP78 are receptor antagonists which may have therapeutic potential for treating patients whose tumors express GRP78 on the cell surface.
Current Appointments & Affiliations
Professor of Pathology
·
1985 - Present
Pathology,
Clinical Science Departments
Recent Publications
An antibody that targets cell-surface glucose-regulated protein-78 inhibits expression of inflammatory cytokines and plasminogen activator inhibitors by macrophages.
Journal Article J Cell Biochem · May 2023 Glucose-regulated protein-78 (Grp78) is an endoplasmic reticulum chaperone, which is secreted by cells and associates with cell surfaces, where it functions as a receptor for activated α2 -macroglobulin (α2 M) and tissue-type plasminogen activator (tPA). I ... Full text Link to item CiteSerum Pro-N-Cadherin Is a Marker of Subclinical Heart Failure in the General Population.
Journal Article J Am Heart Assoc · March 21, 2023 Background We recently reported aberrant processing and localization of the precursor PNC (pro-N-cadherin) protein in failing heart tissues and detected elevated PNC products in the plasma of patients with heart failure. We hypothesize that PNC mislocaliza ... Full text Link to item CitePhysiological 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 CiteRecent Grants
Development of an Optimized Human Antibody to a Novel Target for the Treatment of Fibrotic Diseases
ResearchPrincipal Investigator · Awarded by North Carolina Biotechnology Center · 2019 - 2020Tension-Stat3-miR-mediated Metastasis
ResearchInvestigator · Awarded by City of Hope · 2015 - 2017Clinical Oncology Research Career Development Program
ResearchMentor · Awarded by National Institutes of Health · 2009 - 2015View All Grants
Education, Training & Certifications
Duke University ·
1973
M.D.
Duke University ·
1972
Ph.D.