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

Townsend, Todd A., Jamille Y. Robinson, Tam How, Daniel M. DeLaughter, Gerard C. Blobe, and Joey V. Barnett. “Endocardial cell epithelial-mesenchymal transformation requires Type III TGFβ receptor interaction with GIPC.” Cell Signal 24, no. 1 (January 2012): 247–56. https://doi.org/10.1016/j.cellsig.2011.09.006.

PMID
21945156
Full Text

Baranwal, Somesh, Yanfang Wang, Rajamani Rathinam, Jason Lee, Lianjin Jin, Robin McGoey, Yuliya Pylayeva, Filippo Giancotti, Gerard C. Blobe, and Suresh K. Alahari. “Molecular characterization of the tumor-suppressive function of nischarin in breast cancer.” J Natl Cancer Inst 103, no. 20 (October 19, 2011): 1513–28. https://doi.org/10.1093/jnci/djr350.

PMID
21917605
Full Text

Wong, Nan Soon, Nishan H. Fernando, Johanna C. Bendell, Michael A. Morse, Gerard C. Blobe, Wanda Honeycutt, Herbert Pang, and Herbert I. Hurwitz. “A phase II study of oxaliplatin, dose-intense capecitabine, and high-dose bevacizumab in the treatment of metastatic colorectal cancer.” Clin Colorectal Cancer 10, no. 3 (September 2011): 210–16. https://doi.org/10.1016/j.clcc.2011.03.018.

PMID
21855046
Full Text

Swaminathan, Vinay, Karthikeyan Mythreye, E Tim O’Brien, Andrew Berchuck, Gerard C. Blobe, and Richard Superfine. “Mechanical stiffness grades metastatic potential in patient tumor cells and in cancer cell lines.” Cancer Res 71, no. 15 (August 1, 2011): 5075–80. https://doi.org/10.1158/0008-5472.CAN-11-0247.

PMID
21642375
Full Text

Gatza, Catherine E., Alisha Holtzhausen, Kellye C. Kirkbride, Allyson Morton, Michael L. Gatza, Michael B. Datto, and Gerard C. Blobe. “Type III TGF-β receptor enhances colon cancer cell migration and anchorage-independent growth.” Neoplasia 13, no. 8 (August 2011): 758–70. https://doi.org/10.1593/neo.11528.

PMID
21847367
Full Text

Strickler, J. H., A. L. Cohn, C. Arrowood, S. Haley, M. Morse, H. Uronis, G. C. Blobe, S. D. Hsu, Y. Zafar, and H. Hurwitz. “Phase I study of dasatinib in combination with capecitabine, oxaliplatin, and bevacizumab followed by an expanded cohort in previously untreated metastatic colorectal cancer.” Journal of Clinical Oncology 29, no. 15_suppl (May 20, 2011): 3586–3586. https://doi.org/10.1200/jco.2011.29.15_suppl.3586.

Full Text

Strickler, J. H., A. L. Cohn, C. Arrowood, S. Haley, M. Morse, H. Uronis, G. C. Blobe, S. D. Hsu, Y. Zafar, and H. Hurwitz. “Phase I study of dasatinib in combination with capecitabine, oxaliplatin, and bevacizumab followed by an expanded cohort in previously untreated metastatic colorectal cancer.” J Clin Oncol 29, no. 15_suppl (May 20, 2011): 3586.

PMID
28020244
Scholars@Duke

Hanks, B. A., O. M. Campbell, J. D. Lee, M. Morse, T. M. Clay, H. K. Lyerly, and G. C. Blobe. “Role of the type III TGF-β receptor in modulating antitumor immunity during breast cancer progression.” J Clin Oncol 29, no. 15_suppl (May 20, 2011): 10540.

PMID
28021827
Scholars@Duke

Lambert, Kathleen E., Huang Huang, Karthikeyan Mythreye, and Gerard C. Blobe. “The type III transforming growth factor-β receptor inhibits proliferation, migration, and adhesion in human myeloma cells.” Mol Biol Cell 22, no. 9 (May 2011): 1463–72. https://doi.org/10.1091/mbc.E10-11-0877.

PMID
21411633
Full Text

Starodub, A., A. L. Cohn, C. Arrowood, S. Haley, M. Morse, H. E. Uronis, G. C. Blobe, S. D. Hsu, Y. Zafar, and H. Hurwitz. “Phase I study of dasatinib in combination with capecitabine, oxaliplatin, and bevacizumab followed by an expanded cohort in previously untreated metastatic colorectal cancer.” J Clin Oncol 29, no. 4_suppl (February 2011): 513.

PMID
27985744
Scholars@Duke

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