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

Dugan, Elizabeth, Roxanne Truax, Kellen L. Meadows, Andrew B. Nixon, William P. Petros, Justin Favaro, Nishan H. Fernando, Michael A. Morse, Gerard C. Blobe, and Herbert I. Hurwitz. “A phase I dose-escalation study of imatinib mesylate (Gleevec/STI571) plus capecitabine (Xeloda) in advanced solid tumors..” Anticancer Res 30, no. 4 (April 2010): 1251–56.

PMID
20530436
Scholars@Duke

Ray, Bridgette N., Nam Y. Lee, Tam How, and Gerard C. Blobe. “ALK5 phosphorylation of the endoglin cytoplasmic domain regulates Smad1/5/8 signaling and endothelial cell migration..” Carcinogenesis 31, no. 3 (March 2010): 435–41. https://doi.org/10.1093/carcin/bgp327.

PMID
20042635
Full Text

Lee, Jason D., Nadine Hempel, Nam Y. Lee, and Gerard C. Blobe. “The type III TGF-beta receptor suppresses breast cancer progression through GIPC-mediated inhibition of TGF-beta signaling..” Carcinogenesis 31, no. 2 (February 2010): 175–83. https://doi.org/10.1093/carcin/bgp271.

PMID
19955393
Full Text

Dugan, Elizabeth, Roxanne Truax, Kellen L. Meadows, Gerald C. Blobe, Michael A. Morse, Nishan H. Fernando, Jon P. Gockerman, William P. Petros, and Herbert I. Hurwitz. “Phase I dose escalation study of gemcitabine plus irinotecan in advanced solid tumors..” Anticancer Research 29, no. 12 (December 2009): 5149–53.

PMID
20044630
Scholars@Duke

Lee, Nam Y., John C. Haney, Julie Sogani, and Gerard C. Blobe. “Casein kinase 2beta as a novel enhancer of activin-like receptor-1 signaling..” Faseb J 23, no. 11 (November 2009): 3712–21. https://doi.org/10.1096/fj.09-131607.

PMID
19592636
Full Text

Lee, Nam Y., Kellye C. Kirkbride, Richard D. Sheu, and Gerard C. Blobe. “The transforming growth factor-beta type III receptor mediates distinct subcellular trafficking and downstream signaling of activin-like kinase (ALK)3 and ALK6 receptors..” Molecular Biology of the Cell 20, no. 20 (October 2009): 4362–70. https://doi.org/10.1091/mbc.E09-07-0539.

PMID
19726563
Full Text

Mythreye, Karthikeyan, and Gerard C. Blobe. “The type III TGFbeta receptor regulates directional migration: new tricks for an old dog..” Cell Cycle 8, no. 19 (October 1, 2009): 3069–70. https://doi.org/10.4161/cc.8.19.9419.

PMID
19755845
Full Text

You, Hye Jin, Tam How, and Gerard C. Blobe. “The type III transforming growth factor-beta receptor negatively regulates nuclear factor kappa B signaling through its interaction with beta-arrestin2..” Carcinogenesis 30, no. 8 (August 2009): 1281–87. https://doi.org/10.1093/carcin/bgp071.

PMID
19325136
Full Text

Bullock, K. E., H. I. Hurwitz, H. E. Uronis, M. A. Morse, G. C. Blobe, S. D. Hsu, S. Y. Zafar, A. B. Nixon, L. A. Howard, and J. C. Bendell. “Bevacizumab (B) plus everolimus (E) in refractory metastatic colorectal cancer (mCRC)..” J Clin Oncol 27, no. 15_suppl (May 20, 2009).

PMID
27961646
Scholars@Duke

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