Gerard Blobe
Professor of Medicine
Overview
Our laboratory focuses on transforming growth factor-ß (TGF-ß) superfamily signal transduction pathways, and specifically, the role of these pathways in cancer biology. The TGF-ß superfamily is comprised of a number of polypeptide growth factors, including TGF-βs, bone morphogenetic proteins (BMPs) and activin) that regulate growth, differentiation and morphogenesis in a cell and context specific manner. TGF-ß and the TGF-ß signaling pathway have a dichotomous role in cancer biology, as both tumor-suppressor genes (presumably as regulators of cellular proliferation, differentiation and apoptosis) and as tumor promoters (presumably as regulators of cellular motility, adhesion, angiogenesis and the immune system). This dichotomy of TGF-ß function remains a fundamental problem in the field both in terms of understanding the mechanism of action of the TGF-ß pathway, and directly impacting our ability to target this pathway for the chemoprevention or treatment of human cancers. Resistance to the tumor suppressor effects of TGF-ß is also a common feature of epithelial-derived human cancers (breast, colon, lung, pancreatic, prostate), however, mechanisms for TGF-ß resistance remain undefined in the majority of cases. TGF-ß regulates cellular processes by binding to three high affinity cell surface receptors, the type I, type II, and type III receptors. Recent studies by our laboratory and others have established the type III TGF-ß receptor (TßRIII) as a critical mediator/regulator of TGF-ß signaling. Specifically we have demonstrated that regulating TßRIII expression levels is sufficient to regulate TGF-ß signaling, and that decreased TßRIII expression is a common phenomenon in human cancers, resulting in cancer progression. TßRIII is also shed from the surface to generate soluble TßRIII, which we have demonstrated has a role in creating an immunotolerant tumor microenvironment. The role of TßRIII and soluble TßRIII in the tumor immune microenvironment is currently being investigated using a multidisciplinary approach.
Activin receptor-like kinase 4 (ALK4) is a type I transforming growth factor-β (TGF-β) superfamily receptor that mediates signaling for several TGF-β superfamily ligands, including activin, Nodal and GDF5. We have demonstrated that mutation or copy number loss of ALK4 occurs in 35% of pancreatic cancer patients, with loss of ALK4 expression associated with a poorer prognosis. ALK4 has also been identified in an unbiased screen as a gene whose disruption enhances Ras mediated pancreatic tumorigenesis in vivo. We have demonstrated that loss of ALK4 expression increases canonical TGF-β signaling to increase cancer invasion and metastasis in vivo. We are currently investigating the mechanism by which loss of ALK4 regulates TGF-β signaling, how it may effect other signaling pathways, and how to use this knowledge to treat pancreatic cancer patients with loss of ALK4 function.
Positions
Professor of Medicine in the School of Medicine
2012 School of Medicine
Professor of Pharmacology and Cancer Biology in the School of Medicine
2012 School of Medicine
Professor of Cell Biology in the School of Medicine
2022 School of Medicine
Associate of the Duke Initiative for Science & Society in the Institutes and Provost's Academic Units
2017 Institutes and Provost's Academic Units
Member of the Duke Cancer Institute in the School of Medicine
2002 School of Medicine
Education
M.D. 1995
1995 Duke University
Ph.D. 1995
1995 Duke University
Medical Resident, Medicine
1997 Brigham and Women's Hospital
Adult Oncology Fellow, Medicine
2000 Dana-Farber Cancer Institute
Publications, Grants & Awards
- Grants (50)
- Awards (1)
- Academics Articles (129)
- Conference Pages (22)
- Book Sections (1)
National Institutes of Health
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University of North Carolina - Chapel Hill
National Institutes of Health
National Cancer Center
National Institutes of Health
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American Society for Pharmacology and Experimental Therapeutics
Susan G. Komen Breast Cancer Foundation
Susan G. Komen Breast Cancer Foundation
National Institutes of Health
National Institutes of Health
National Institutes of Health
Melanoma Research Alliance
National Institutes of Health
HHT Foundation International, Inc.
Triangle Community Foundation
National Institutes of Health
National Cancer Institute
Alex's Lemonade Stand
Alex's Lemonade Stand
National Institutes of Health
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National Institutes of Health
Department of Defense
National Institutes of Health
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National Institutes of Health
American Association for the Advancement of Science
Cancer Medicine
Molecular Biology of the Cell
Cancer Chemother Pharmacol
Cancer Immunol Res
Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology
Arterioscler Thromb Vasc Biol
Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology
Cancer Chemother Pharmacol
Biochem Soc Trans
Scientific Reports
Molecular Biology of the Cell
Drugs of the Future
Molecular Biology of the Cell
J Mol Med (Berl)
Molecular Biology of the Cell
Molecular Biology of the Cell
Molecular Biology of the Cell
Trends in Biochemical Sciences
Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology
Clinical Cancer Research
Molecular Cancer Therapeutics
J Clin Invest
J Clin Invest
The Biochemical Journal
Molecular Biology of the Cell
The Embo Journal
Molecular Biology of the Cell
Cancer Chemother Pharmacol
Cancer Research
J Natl Cancer Inst
Clinical Colorectal Cancer
Cancer Res
Neoplasia
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology
Journal of Clinical Oncology
Molecular Biology of the Cell
Journal of Clinical Oncology
Cancer Chemother Pharmacol
Anticancer Res
Cells Tissues Organs
Cancer Research
Anticancer Res
Carcinogenesis
Carcinogenesis
Anticancer Res
Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology
Cell Cycle
Molecular Biology of the Cell
Journal of Clinical Oncology
Journal of Clinical Oncology
Proc Natl Acad Sci U S A
The Journal of Biological Chemistry
The Journal of Biological Chemistry
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Biochimica Et Biophysica Acta
The Journal of Biological Chemistry
The Journal of Biological Chemistry
International Journal of Radiation Oncology, Biology, Physics
International Journal of Radiation Oncology, Biology, Physics
Cancer Research
The Journal of Clinical Investigation
Journal of Clinical Oncology
Trends in Biochemical Sciences
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Annals of Surgical Oncology
Genome Research
Expert Opinion on Biological Therapy
The Journal of Biological Chemistry
The Journal of Biological Chemistry
The Journal of Biological Chemistry
The Journal of Biological Chemistry
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
The New England Journal of Medicine
Current Opinion in Otolaryngology & Head and Neck Surgery
The Journal of Biological Chemistry
The Journal of Biological Chemistry
The Journal of Biological Chemistry
The Journal of Biological Chemistry
Cancer Surveys
Cellular Signalling
Prostaglandins, Leukotrienes, and Essential Fatty Acids
Cancer Metastasis Reviews
The Journal of Biological Chemistry
The Journal of Biological Chemistry
Clinical Research
Clinical Research
Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research
Journal of Cellular Biochemistry
The Journal of Biological Chemistry
Faseb Journal
Clinical Research
The Journal of Biological Chemistry
The Journal of Biological Chemistry
The Journal of Biological Chemistry
Clinical Research
The Journal of Biological Chemistry
The Journal of Biological Chemistry
Annals of Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
International Journal of Radiation Oncology, Biology, Physics
International Journal of Radiation Oncology, Biology, Physics
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Angiogenesis
Cancer Research
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
J Mol Med (Berl)
Cancer Research
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Cancer Research
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Molecular Biology of the Cell
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
The Journal of Urology
Molecular Biology of the Cell
TGF-B in Human Disease
DCI Centers, Cancer Types & Labs
Offices & Contact
Durham, NC
27708 Duke Box 91004
Durham, NC
27708-1004