Gerard Conrad Blobe, MD, PhD

Professor of Medicine
Professor of Pharmacology and Cancer Biology
Associate of the Duke Initiative for Science & Society
Member of the Duke Cancer Institute
Campus mail B354 Levine Science Research Center, 450 Research Drive, Durham, NC 27708
Phone (919) 668-6688

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.

Education and Training

  • Adult Oncology Fellow, Medicine, Dana Farber Cancer Institute, 1997 - 2000
  • Medical Resident, Medicine, Brigham and Women's Hospital, 1995 - 1997
  • Ph.D., Duke University, 1995
  • M.D., Duke University, 1995

Publications

Blobe, G. C., S. Stribling, L. M. Obeid, and Y. A. Hannun. “Protein kinase C isoenzymes: regulation and function..” Cancer Surv 27 (1996): 213–48.

PMID
8909803
Scholars@Duke

Khan, W. A., G. C. Blobe, and Y. A. Hannun. “Arachidonic acid and free fatty acids as second messengers and the role of protein kinase C..” Cell Signal 7, no. 3 (March 1995): 171–84. https://doi.org/10.1016/0898-6568(94)00089-t.

PMID
7662506
Full Text

Blobe, G. C., W. A. Khan, and Y. A. Hannun. “Protein kinase C: cellular target of the second messenger arachidonic acid?.” Prostaglandins Leukot Essent Fatty Acids 52, no. 2–3 (February 1995): 129–35. https://doi.org/10.1016/0952-3278(95)90011-x.

PMID
7784448
Full Text

Blobe, G. C., L. M. Obeid, and Y. A. Hannun. “Regulation of protein kinase C and role in cancer biology..” Cancer Metastasis Rev 13, no. 3–4 (December 1994): 411–31. https://doi.org/10.1007/bf00666107.

PMID
7712599
Full Text

Venable, M. E., G. C. Blobe, and L. M. Obeid. “Identification of a defect in the phospholipase D/diacylglycerol pathway in cellular senescence..” J Biol Chem 269, no. 42 (October 21, 1994): 26040–44.

PMID
7929315
Scholars@Duke

BLOBE, G. C., and Y. A. HANNUN. “DETERMINATION OF A NEW FUNCTIONAL DOMAIN FOR PROTEIN-KINASE-C WHICH DIRECTS ISOENZYME SPECIFIC PROTEIN-PROTEIN INTERACTIONS.” Clinical Research 42, no. 2 (April 1, 1994): A114–A114.

Scholars@Duke

RICHARDS, A. L., W. A. KHAN, G. C. BLOBE, and Y. A. HANNUN. “A NOVEL CALCIUM-INDEPENDENT AND PHOSPHATIDIC ACID-ACTIVATED PROTEIN-KINASE DISCOVERED IN HUMAN PLATELETS.” Clinical Research 42, no. 2 (April 1, 1994): A114–A114.

Scholars@Duke

Gamard, C. J., G. C. Blobe, Y. A. Hannun, and L. M. Obeid. “Specific role for protein kinase C beta in cell differentiation..” Cell Growth & Differentiation : The Molecular Biology Journal of the American Association for Cancer Research 5, no. 4 (April 1994): 405–9.

PMID
8043514
Scholars@Duke

Khan, W. A., G. C. Blobe, A. L. Richards, and Y. A. Hannun. “Identification, partial purification, and characterization of a novel phospholipid-dependent and fatty acid-activated protein kinase from human platelets..” The Journal of Biological Chemistry 269, no. 13 (April 1994): 9729–35.

PMID
8144564
Scholars@Duke

BLOBE, G. C., D. FABBRO, S. STABEL, and Y. A. HANNUN. “IDENTIFICATION OF SEQUENCE-SPECIFIC INTERACTIONS OF PROTEIN-KINASE-C ISOENZYMES WITH THE ACTIN CYTOSKELETON.” Journal of Cellular Biochemistry, January 1, 1994, 81–81.

Scholars@Duke

Pages