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., W. A. Khan, A. E. Halpern, L. M. Obeid, and Y. A. Hannun. “Selective regulation of expression of protein kinase C beta isoenzymes occurs via alternative splicing..” The Journal of Biological Chemistry 268, no. 14 (May 1993): 10627–35.

PMID
7683684
Scholars@Duke

BLOBE, G. C., D. FABBRO, and Y. A. HANNUN. “DETERMINATION OF THE FUNCTIONAL DIFFERENCES BETWEEN PROTEIN-KINASE-C BETA(1) AND BETA(II) ISOENZYMES.” Faseb Journal 7, no. 7 (April 20, 1993): A1119–A1119.

Scholars@Duke

BLOBE, G. C., D. FABBRO, L. M. OBEID, and Y. A. HANNUN. “SELECTIVE TRANSLOCATION OF PROTEIN-KINASE-C BETA-I AND BETA-II ISOENZYMES TO THE CYTOSKELETON.” Clinical Research 41, no. 2 (April 1, 1993): A242–A242.

Scholars@Duke

Khan, W. A., G. Blobe, A. Halpern, W. Taylor, W. C. Wetsel, D. Burns, C. Loomis, and Y. A. Hannun. “Selective regulation of protein kinase C isoenzymes by oleic acid in human platelets..” J Biol Chem 268, no. 7 (March 5, 1993): 5063–68.

PMID
8444883
Scholars@Duke

Blobe, G. C., C. W. Sachs, W. A. Khan, D. Fabbro, S. Stabel, W. C. Wetsel, L. M. Obeid, R. L. Fine, and Y. A. Hannun. “Selective regulation of expression of protein kinase C (PKC) isoenzymes in multidrug-resistant MCF-7 cells. Functional significance of enhanced expression of PKC alpha..” J Biol Chem 268, no. 1 (January 5, 1993): 658–64.

PMID
8093247
Scholars@Duke

Obeid, L. M., G. C. Blobe, L. A. Karolak, and Y. A. Hannun. “Cloning and characterization of the major promoter of the human protein kinase C beta gene. Regulation by phorbol esters..” J Biol Chem 267, no. 29 (October 15, 1992): 20804–10.

PMID
1400396
Scholars@Duke

BLOBE, G. C., A. E. HALPERN, Y. A. HANNUN, and L. M. OBEID. “SELECTIVE REGULATION OF ALTERNATIVELY SPLICED PROTEIN-KINASE-C ISOENZYMES.” Clinical Research 40, no. 2 (April 1, 1992): A243–A243.

Scholars@Duke

BLOBE, G. C., W. A. KHAN, W. C. WETSEL, L. M. OBEID, R. L. FINE, and Y. A. HANNUN. “A ROLE FOR SPECIFIC PROTEIN-KINASE-C ISOENZYMES IN MODULATING THE MULTIDRUG RESISTANT PHENOTYPE.” Clinical Research 40, no. 2 (April 1, 1992): A375–A375.

Scholars@Duke

Khan, W. A., G. C. Blobe, and Y. A. Hannun. “Activation of protein kinase C by oleic acid. Determination and analysis of inhibition by detergent micelles and physiologic membranes: requirement for free oleate..” J Biol Chem 267, no. 6 (February 25, 1992): 3605–12.

PMID
1740412
Scholars@Duke

Huber, P. W., G. C. Blobe, and K. M. Hartmann. “Conformational studies of the nucleic acid binding sites for Xenopus transcription factor IIIA..” J Biol Chem 266, no. 5 (February 15, 1991): 3278–86.

PMID
1993700
Scholars@Duke

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