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

Finger, Elizabeth C., Ryan S. Turley, Mei Dong, Tam How, Timothy A. Fields, and Gerard C. Blobe. “TbetaRIII suppresses non-small cell lung cancer invasiveness and tumorigenicity..” Carcinogenesis 29, no. 3 (March 2008): 528–35. https://doi.org/10.1093/carcin/bgm289.

PMID
18174241
Full Text

Gordon, Kelly J., Mei Dong, Elizabeth M. Chislock, Timothy A. Fields, and Gerard C. Blobe. “Loss of type III transforming growth factor beta receptor expression increases motility and invasiveness associated with epithelial to mesenchymal transition during pancreatic cancer progression..” Carcinogenesis 29, no. 2 (February 2008): 252–62. https://doi.org/10.1093/carcin/bgm249.

PMID
17999987
Full Text

You, Hye Jin, Monique W. Bruinsma, Tam How, Julie H. Ostrander, and Gerard C. Blobe. “The type III TGF-beta receptor signals through both Smad3 and the p38 MAP kinase pathways to contribute to inhibition of cell proliferation..” Carcinogenesis 28, no. 12 (December 2007): 2491–2500. https://doi.org/10.1093/carcin/bgm195.

PMID
17768179
Full Text

Lee, Nam Y., and Gerard C. Blobe. “The interaction of endoglin with beta-arrestin2 regulates transforming growth factor-beta-mediated ERK activation and migration in endothelial cells..” J Biol Chem 282, no. 29 (July 20, 2007): 21507–17. https://doi.org/10.1074/jbc.M700176200.

PMID
17540773
Full Text

Hempel, Nadine, Tam How, Mei Dong, Susan K. Murphy, Timothy A. Fields, and Gerard C. Blobe. “Loss of betaglycan expression in ovarian cancer: role in motility and invasion..” Cancer Res 67, no. 11 (June 1, 2007): 5231–38. https://doi.org/10.1158/0008-5472.CAN-07-0035.

PMID
17522389
Full Text

Czito, Brian G., Johanna C. Bendell, Christopher G. Willett, Michael A. Morse, Gerard C. Blobe, Douglas S. Tyler, John Thomas, et al. “Bevacizumab, oxaliplatin, and capecitabine with radiation therapy in rectal cancer: Phase I trial results..” Int J Radiat Oncol Biol Phys 68, no. 2 (June 1, 2007): 472–78. https://doi.org/10.1016/j.ijrobp.2007.02.001.

PMID
17498568
Full Text

Turley, Ryan S., Elizabeth C. Finger, Timothy A. Fields, and Gerard C. Blobe. “281: The Role of the Type III TGF-BETA Receptor in Prostate Cancer.” In Journal of Urology, 177:94–94. Ovid Technologies (Wolters Kluwer Health), 2007. https://doi.org/10.1016/s0022-5347(18)30546-9.

Full Text

Czito, Brian G., Chris R. Kelsey, Herbert I. Hurwitz, Chris G. Willett, Michael A. Morse, Gerard C. Blobe, Nishan H. Fernando, et al. “A Phase I study of capecitabine, carboplatin, and paclitaxel with external beam radiation therapy for esophageal carcinoma..” Int J Radiat Oncol Biol Phys 67, no. 4 (March 15, 2007): 1002–7. https://doi.org/10.1016/j.ijrobp.2006.10.027.

PMID
17197129
Full Text

Turley, Ryan S., Elizabeth C. Finger, Nadine Hempel, Tam How, Timothy A. Fields, and Gerard C. Blobe. “The type III transforming growth factor-beta receptor as a novel tumor suppressor gene in prostate cancer..” Cancer Res 67, no. 3 (February 1, 2007): 1090–98. https://doi.org/10.1158/0008-5472.CAN-06-3117.

PMID
17283142
Full Text

Dong, Mei, Tam How, Kellye C. Kirkbride, Kelly J. Gordon, Jason D. Lee, Nadine Hempel, Patrick Kelly, Benjamin J. Moeller, Jeffrey R. Marks, and Gerard C. Blobe. “The type III TGF-beta receptor suppresses breast cancer progression..” J Clin Invest 117, no. 1 (January 2007): 206–17. https://doi.org/10.1172/JCI29293.

PMID
17160136
Full Text

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