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 as a critical mediator/regulator of TGF-ß signaling. Specifically we have demonstrated that regulating type III TGF-ß receptor expression levels is sufficient to regulate TGF-ß signaling, and that decreased type III receptor expression is a common phenomenon in human cancers, resulting in cancer progression. The role of the type III TGF-ß receptor and type III TGF-ß receptor-interacting proteins in TGF-ß signaling and cancer biology and the epithelial to mesenchymal transition that occurs in human breast, colon and pancreatic cancers are currently being investigated using a multidisciplinary approach.
TGF-ß and the TGF-ß superfamily signaling pathways also have an important role in vascular biology. Indeed, mutations in two endothelial specific TGF-ß superfamily receptors, endoglin and ALK-1 (a type I receptor in the TGF-ß family), are responsible for the human vascular disease, hereditary hemorrhagic telangiectasia (HHT), and mice which lack expression of these receptors are embryonic lethal due to defects in angiogenesis. In addition, endoglin expression is potently up regulated during tumor-induced angiogenesis. In endothelial cells, TGF-ß signals through the type I TGF-ß receptor (ALK-5) or through ALK-1, to mediate opposing effects on endothelial cell proliferation and migration. However, the role of endoglin in regulating the balance in signaling between these pathways is unknown. Our laboratory has identified the nuclear hormone receptor, LXR-ß, as a protein that binds to activated ALK-1, is phosphorylated by ALK-1 and modulates ALK-1 signaling,establishing a novel signaling pathway downstream of ALK-1. Investigations in our laboratory have also revealed important functions for the cytoplasmic domain of endoglin, which is highly homologous to the cytoplasmic domain of the type III TGF-ß receptor. Studies are currently underway to further elucidate the signal transduction pathway downstream from these receptors and to establish their role in regulating tumor-induced angiogenesis. The ultimate goal of these studies is the ability to target the TGF-ß pathway for the chemoprevention or treatment of human cancers.
As endoglin and the type III TGF-ß receptors are both "co-receptors," a class of poorly understood cell surface receptors that bind ligand but are not thought to signal directly, another focus for the laboratory is establishing the role of these co-receptors in orchestrating signaling in physiological and pathophysiological settings.

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., D. S. Stribling, D. Fabbro, S. Stabel, and Y. A. Hannun. “Protein kinase C beta II specifically binds to and is activated by F-actin (vol 271, pg 15823, 1996).” Journal of Biological Chemistry 271, no. 47 (November 22, 1996): 30297–30297.

Scholars@Duke

Jideama, N. M., T. A. Noland, R. L. Raynor, G. C. Blobe, D. Fabbro, M. G. Kazanietz, P. M. Blumberg, Y. A. Hannun, and J. F. Kuo. “Phosphorylation specificities of protein kinase C isozymes for bovine cardiac troponin I and troponin T and sites within these proteins and regulation of myofilament properties..” J Biol Chem 271, no. 38 (September 20, 1996): 23277–83. https://doi.org/10.1074/jbc.271.38.23277.

PMID
8798526
Full Text

Blobe, G. C., D. S. Stribling, D. Fabbro, S. Stabel, and Y. A. Hannun. “Protein kinase C beta II specifically binds to and is activated by F-actin..” J Biol Chem 271, no. 26 (June 28, 1996): 15823–30. https://doi.org/10.1074/jbc.271.26.15823.

PMID
8663149
Full Text

Blobe, G. C., D. S. Stribling, D. Fabbro, S. Stabel, and Y. A. Hannun. “Erratum: Protein kinase C βII specifically binds to and is activated by F-actin (Journal of Biological Chemistry (1996) 271 (15823-15830)).” Journal of Biological Chemistry 271, no. 47 (January 1, 1996).

Scholars@Duke

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.

PMID
7662506
Scholars@Duke

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.

PMID
7784448
Scholars@Duke

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.

PMID
7712599
Scholars@Duke

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

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..” J Biol Chem 269, no. 13 (April 1, 1994): 9729–35.

PMID
8144564
Scholars@Duke

Pages