Dr. Gerard C. Blobe

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Duke University
Duke University Medical Center
Medical Oncology
Associate ProfessorAppointed: 2006
Duke University
Duke University Medical Center
Pharmacology and Cancer Biology
Associate ProfessorAppointed: 2008
Professional Headshot of Gerard C. Blobe

Mailing Address

B354 LSRC, Research Drive
Box 91004
Durham, North Carolina 27708
United States

Contact Information

Phone: (919) 668-1352
Fax: (919) 681-6906
blobe001@mc.duke.edu

Qualifications

M.D., Duke University, 1995.
Ph.D., Duke University, Cell Biology, 1995.
B.S., University of Notre Dame, Chemistry, 1988.

Expertise and Research Interests

Our laboratory focuses on the transforming growth factor-beta (TGF-beta) superfamly signal transduction pathway, and specifically, the role of this pathway in cancer and vascular biology. The TGF-beta superfamily is comprised of a large number of polypeptide growth factors that regulate growth, differentiation, and morphogenesis in a cell and context specific manner. TGF-beta and the TGF-beta 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-beta function remains a fundamental problem in the field both in terms of understanding the mechanism of action of the TGF-beta 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-beta is also a common feature of epithelial-derived human cancers (breast, colon, lung, pancreatic, prostate), however, mechanisms for TGF-beta resistance remain undefined in the majority of cases. TGF-beta 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 implicated the type III TGF-beta receptor as a critical mediator/regulator of TGF-beta signaling. Specifically we and others have demonstrated that the type III TGF-beta receptor can either increase or decrease TGF-beta signaling, and that the type III TGF-beta receptor is a tumor suppressor in a broad spectrum of human cancers. The role of the type III TGF-beta receptor and type III TGF-beta receptor -interacting proteins in TGF-beta signaling, cancer and vascular 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-beta and the TGF-beta signaling pathway also have an important role in vascular biology. Indeed, mutations in two endothelial specific TGF-beta receptors, endoglin and ALK-1 (a type I receptor in the TGF-beta 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. Although endoglin and ALK-1 both bind TGF-beta and form a complex together, neither has been shown to signal in response to TGF-beta, thus the signaling pathway downstream of endoglin and ALK-1 is unknown. Our laboratory has identified the nuclear hormone receptor, LXR-beta, as a protein that binds to activated ALK-1, is phosphorylated by ALK-1 and modulates ALK-1 signaling, providing the first insight into the 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-beta receptor. Studies are currently underway to identify the ligand for these receptors, 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-beta pathway for the chemopreventionor treatment of human cancers.

Other Expertise

Clinical/Translational Interests:
I am involved in the Gastrointestinal Cancer/Experimental Therapeutics group at Duke University Medical Center to focus on translational research and clinical treatment of patients with these tumors. Gastrointestinal tumors, particularly colon and pancretic cancer, provide a system amenable to study as mouse models and tissue specimens from various stages of tumorigenesis are available. In addition, genetic syndromes involving gastrointestinal tumors and a molecular framework of progression of colon cancers have been identified providing further leads for study. Finally, many gastrointestinal tumors, including gastric and colorectal cancer, are readily accessible making them ideal candidates for establishing and applying advances in research in terms of prevention, screening, diagnosis and treatment.

Keywords

COS Keywords:

Angiogenesis, Biomedical Research (Multidisciplinary), Breast Cancer, Cancer Biology, Cell Biology, Cell Differentiation, Chemoprevention, Clinical Medicine, Growth Factors, Health and Medicine, Internal Medicine, Lung Cancer, Medical Education, Morphogenesis, Oncology, Pharmacology, Prostate Cancer, Receptors, Signal Transduction, Vascular Biology, Vascular Diseases or Injury.

Additional Terms:

Angiogenesis, Bone Morphogenetic Protein, Cancer Biology, Co-receptors, Colon Cancer, Pancreatic Cancer, Signal Transduction, TGF-beta, Transforming Growth Factor Beta, Vascular Biology.

Languages

(Reading, Writing, Speaking)

English: (Fluent, Fluent, Fluent)
German: (Basic, Basic, Basic)

Memberships

Alliance for Cell Signalling
American Academy for the Advancement of Science
American Association for Cancer Research
American College of Physicians
American Medical Association
American Society for Biochemistry and Molecular Biology
American Society for Clinical Investigation
American Society for Clinical Oncology
Federation of American Societies for Experimental Biology
Massachusetts Medical Society

Honors and Awards

2008, American Society of Clinical Investigation Membership, ASCI, Duke University
2006, Joklik Cancer Research Award, Duke University Comprehensive Cancer Center, Duke University
2005, AACR Gertrude B. Elion Cancer Research Award, American Association for Cancer Research, Duke University
2004-2008, ACS Research Scholar, ACS, Duke University
2003, V Scholar, V Foundation for Cancer Research, Duke University
2001-2004, NCI Transition Career Development Award, NIH/NCI, Duke University
1998-2000, Postdoctoral Research Fellowship for Physicians, Howard Hughes Medical Institute, Whitehead Institute for Biomedical Research
1988-1995, Medical Scientist Training Program Fellowship, National Institutes of Health, Duke University
1984-1988, Notre Dame Scholar, University of Notre Dame

Previous Positions

2000-2000, Instructor, Harvard University, Medical School
2000-2000, Instructor, Massachusetts General Hospital, Harvard Medical School, Medicine
2000-2006, Assistant Professor, Duke University, School of Medicine, Medicine, Medical Oncology
1998-2000, Visiting Scientist, Whitehead Institute for Biomedical Research
1997-2000, Fellowship, Dana-Farber Cancer Institute, Harvard Medical School, Adult Oncology
1995-1997, Resident, Harvard University, Brigham and Women's Hospital, Internal Medicine

Funding Received

  • Howard Hughes Medical Institute: Postdoctoral Research Fellowship for Physicians, Sep 1, 1998 to Dec 31, 2000.
  • National Institutes of Health (NIH): RO1, Role of the Type III TGF-beta Receptor in Cancer Biology, May 1, 2004 to Apr 30, 2008.
  • American Cancer Society (ACS): Identification of Novel TGF-beta Receptors, Jun 2001 to Jun 2002.
  • American Cancer Society (ACS): TbetaRIII as a Mediator/Regulator of Signaling, Jul 1, 2004 to 2005.
  • American Heart Association (AHA): ALK-1 Signaling in Endothelial Cells, Jul 1, 2003 to Jun 30, 2005.
  • National Institutes of Health (NIH): K22-NCI Transition Career Development Award, Apr 2002 to Mar 2005.
  • National Institutes of Health (NIH): R01, ALK-1 and Endoglin Signaling in Endothelial Cells, Apr 1, 2004 to Mar 31, 2009.
  • National Institutes of Health (NIH): R01-ROLE OF TbetaRIII IN REGULATING MOTILITY AND INVASION, 2009 to 2014.
  • National Institutes of Health (NIH): R01-FUNCTION OF TetaRIII AS A BMP CO-RECEPTOR IN HUMAN CANCER, 2009 to 2014.
  • National Institutes of Health (NIH): R01, Type III Beta Receptor as a Mediator/Reg. of Signaling, 2005 to 2010.
  • Pardee Foundation: Role of TbetaRIII in EMT, 2003 to 2004.

Publications

  • You HJ, How T, Blobe GC (Aug 2009) The type III transforming growth factor-beta receptor negatively regulates nuclear factor kappa B signaling through its interaction with beta-arrestin2., Carcinogenesis, 30 (8), 1281-7 Abstract
  • Lee NY, Haney JC, Sogani J, Blobe GC (Jul 2009) Casein kinase 2{beta} as a novel enhancer of activin-like receptor-1 signaling., The FASEB journal : official publication of the Federation of American Societies for Experimental Biology Abstract
  • Mythreye K, Blobe GC (May 2009) The type III TGF-beta receptor regulates epithelial and cancer cell migration through beta-arrestin2-mediated activation of Cdc42., Proceedings of the National Academy of Sciences of the United States of America, 106 (20), 8221-6 Abstract
  • Mythreye K, Blobe GC (May 2009) Proteoglycan signaling co-receptors: Roles in cell adhesion, migration and invasion., Cellular signalling Abstract
  • Gordon KJ, Kirkbride KC, How T, Blobe GC (Feb 2009) Bone morphogenetic proteins induce pancreatic cancer cell invasiveness through a Smad1-dependent mechanism that involves matrix metalloproteinase-2., Carcinogenesis, 30 (2), 238-48 Abstract
  • Finger EC, Lee NY, You HJ, Blobe GC (Dec 2008) Endocytosis of the type III transforming growth factor-beta (TGF-beta) receptor through the clathrin-independent/lipid raft pathway regulates TGF-beta signaling and receptor down-regulation., The Journal of biological chemistry, 283 (50), 34808-18 Abstract
  • Lee NY, Ray B, How T, Blobe GC (Nov 2008) Endoglin promotes transforming growth factor beta-mediated Smad 1/5/8 signaling and inhibits endothelial cell migration through its association with GIPC., The Journal of biological chemistry, 283 (47), 32527-33 Abstract
  • Hempel N, How T, Cooper SJ, Green TR, Dong M, Copland JA, Wood CG, Blobe GC (May 2008) Expression of the type III TGF-beta receptor is negatively regulated by TGF-beta., Carcinogenesis, 29 (5), 905-12 Abstract
  • Gordon KJ, Blobe GC (Apr 2008) Role of transforming growth factor-beta superfamily signaling pathways in human disease., Biochimica et biophysica acta, 1782 (4), 197-228 Abstract
  • Finger EC, Turley RS, Dong M, How T, Fields TA, Blobe GC (Mar 2008) TbetaRIII suppresses non-small cell lung cancer invasiveness and tumorigenicity., Carcinogenesis, 29 (3), 528-35 Abstract
  • Kirkbride KC, Townsend TA, Bruinsma MW, Barnett JV, Blobe GC (Mar 2008) Bone morphogenetic proteins signal through the transforming growth factor-beta type III receptor., The Journal of biological chemistry, 283 (12), 7628-37 Abstract
  • Gordon KJ, Dong M, Chislock EM, Fields TA, Blobe GC (Feb 2008) 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 (2), 252-62 Abstract
  • You HJ, Bruinsma MW, How T, Ostrander JH, Blobe GC (Dec 2007) 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 (12), 2491-500 Abstract
  • Lee NY, Blobe GC (Jul 2007) The interaction of endoglin with beta-arrestin2 regulates transforming growth factor-beta-mediated ERK activation and migration in endothelial cells., The Journal of biological chemistry, 282 (29), 21507-17 Abstract
  • Czito BG, Bendell JC, Willett CG, Morse MA, Blobe GC, Tyler DS, Thomas J, Ludwig KA, Mantyh CR, Ashton J, Yu D, Hurwitz HI (Jun 2007) Bevacizumab, oxaliplatin, and capecitabine with radiation therapy in rectal cancer: Phase I trial results., International journal of radiation oncology, biology, physics, 68 (2), 472-8 Abstract
  • Hempel N, How T, Dong M, Murphy SK, Fields TA, Blobe GC (Jun 2007) Loss of betaglycan expression in ovarian cancer: role in motility and invasion., Cancer research, 67 (11), 5231-8 Abstract
  • Czito BG, Kelsey CR, Hurwitz HI, Willett CG, Morse MA, Blobe GC, Fernando NH, D'Amico TA, Harpole DH, Honeycutt W, Yu D, Bendell JC (Mar 2007) A Phase I study of capecitabine, carboplatin, and paclitaxel with external beam radiation therapy for esophageal carcinoma., International journal of radiation oncology, biology, physics, 67 (4), 1002-7 Abstract
  • Turley RS, Finger EC, Hempel N, How T, Fields TA, Blobe GC (Feb 2007) The type III transforming growth factor-beta receptor as a novel tumor suppressor gene in prostate cancer., Cancer research, 67 (3), 1090-8 Abstract
  • Dong M, How T, Kirkbride KC, Gordon KJ, Lee JD, Hempel N, Kelly P, Moeller BJ, Marks JR, Blobe GC (Jan 2007) The type III TGF-beta receptor suppresses breast cancer progression., The Journal of clinical investigation, 117 (1), 206-17 Abstract
  • Czito, B.G. Kelsey, C.R., Hurwitz, H.I., Willett C.G., Morse M.A., Blobe G.C., Fernando N.H., D'Amico T.A., Harpole D.H., Honeycutt W., Yu D., Bendell J.C. (2007) A Phase I study of capecitabine, carboplatin, and paclitaxel with external beam radiation therapy for esophageal carcinoma., Int J Radiat Oncol Biol Phys., 67, 1002-7
  • Dong M, Blobe GC (Jun 2006) Role of transforming growth factor-beta in hematologic malignancies., Blood, 107 (12), 4589-96 Abstract
  • White RR, Xie HB, Gottfried MR, Czito BG, Hurwitz HI, Morse MA, Blobe GC, Paulson EK, Baillie J, Branch MS, Jowell PS, Clary BM, Pappas TN, Tyler DS (Mar 2005) Significance of histological response to preoperative chemoradiotherapy for pancreatic cancer., Annals of Surgical Oncology : the Official Journal of the Society of Surgical Oncology., 12 (3), 214-21 Abstract
  • Elliott RL, Blobe GC (Mar 2005) Role of transforming growth factor Beta in human cancer., Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology., 23 (9), 2078-93 Abstract
  • Kirkbride, K.C., Ray, B., Blobe, G.C. (2005) Cell Surface Co-Receptors: Emerging Roles in Signaling and Human Disease, Trends in Biochemical Sciences, 30, 611-21
  • Chen W, Kirkbride KC, How T, Nelson CD, Mo J, Frederick JP, Wang XF, Lefkowitz RJ, Blobe GC, Beta-arrestin 2 mediates endocytosis of type III TGF-beta receptor and down-regulation of its signaling, Science, 301(5638), 1394-7, September 2003 Abstract
  • Kirkbride KC, Blobe GC, Inhibiting the TGF-beta signalling pathway as a means of cancer immunotherapy, Expert Opinion On Biological Therapy, 3(2), 251-61, April 2003
  • Mo J, Fang SJ, Chen W, Blobe GC, Regulation of ALK-1 signaling by the nuclear receptor LXRbeta, Journal of Biological Chemistry, 277(52), 50788-94, December 2002 Abstract
  • Mo J, Fang SJ, Chen W, Blobe GC (Dec 2002) Regulation of ALK-1 signaling by the nuclear receptor LXRbeta., The Journal of biological chemistry, 277 (52), 50788-94 Abstract
  • Schiemann WP, Blobe GC, Kalume DE, Pandey A, Lodish HF, Context-specific effects of fibulin-5 (DANCE/EVEC) on cell proliferation, motility, and invasion. Fibulin-5 is induced by transforming growth factor-beta and affects protein kinase cascade, Journal of Biological Chemistry, 277(30), 27367-77, July 2002 Abstract
  • Blobe GC, Liu X, Fang SJ, How T, and Lodish HF., A Novel Mechanism for Regulating Transforming Growth Factor beta Signaling: Functional Modulation of Type III TGF-beta receptor expression through interaction with the PDZ domain protein, GIPC, Journal of Biological Chemistry, 276, 39608-39617, October 2001
  • Blobe GC, Schiemann WP, Pepin MC, Beauchemin M, Moustakas A, Lodish HF, O'Connor-McCourt MD, Functional roles for the cytoplasmic domain of the type III transforming growth factor beta receptor in regulating transforming growth factor beta signaling, Journal of Biological Chemistry, 276(27), 24627-37, 2001 Abstract
  • Blobe GC, Mantel M, Janicek M, Demetri GD, Two patients with sarcoma. Case 2. Uterine sarcoma, Journal of Clinical Oncology, 18(11), 2343-4, June 2000 Abstract
  • Blobe GC, Schiemann WP, Lodish HF, Role of transforming growth factor beta in human disease, New England Journal of Medicine, 342(18), 1350-8, May 2000 Abstract
  • Jideama NM, Noland TA Jr, Raynor RL, Blobe GC, Fabbro D, Kazanietz MG, Blumberg PM, Hannun YA, Kuo JF, 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, Journal of Biological Chemistry, 271(38), 23277-83, September 1996 Abstract
  • Blobe GC, Stribling DS, Fabbro D, Stabel S, Hannun YA, Protein kinase C beta II specifically binds to and is activated by F-actin [published erratum appears in J Biol Chem 1996 Nov 22, Journal of Biological Chemistry, 271(26), 15823-30, June 1996 Abstract
  • Blobe GC, Stribling S, Obeid LM, Hannun YA, Protein kinase C isoenzymes: regulation and function, Cancer Surveys, 27, 213-48, 1996 Abstract
  • Khan WA, Blobe GC, Hannun YA, Arachidonic acid and free fatty acids as second messengers and the role of protein kinase C, Cellular Signalling, 7(3), 171-84, March 1995 Abstract
  • Blobe GC, Khan WA, Hannun YA, Protein kinase C: cellular target of the second messenger arachidonic acid?, Prostaglandins Leukotrienes and Essential Fatty Acids, 52(2-3), 129-35, 1995 Abstract
  • Blobe GC, Obeid LM, Hannun YA, Regulation of protein kinase C and role in cancer biology, Cancer and Metastasis Reviews, 13(3-4), 411-31, December 1994 Abstract
  • Venable ME, Blobe GC, Obeid LM, Identification of a defect in the phospholipase D/diacylglycerol pathway in cellular senescence, Journal of Biological Chemistry, 269(42), 26040-4, October 1994 Abstract
  • Gamard CJ, Blobe GC, Hannun YA, Obeid LM, Specific role for protein kinase C beta in cell differentiation, Cell Growth and Differentiation, 5(4), 405-9, April 1994 Abstract
  • Khan WA, Blobe GC, Richards AL, Hannun YA, Identification, partial purification, and characterization of a novel phospholipid-dependent and fatty acid-activated protein kinase from human platelets, Journal of Biological Chemistry, 269(13), 9729-35, April 1994 Abstract
  • Blobe GC, Khan WA, Halpern AE, Obeid LM, Hannun YA, Selective regulation of expression of protein kinase C beta isoenzymes occurs via alternative splicing, Journal of Biological Chemistry, 268(14), 10627-35, May 1993 Abstract
  • Blobe GC, Sachs CW, Khan WA, Fabbro D, Stabel S, Wetsel WC, Obeid LM, Fine RL, Hannun YA, Selective regulation of expression of protein kinase C (PKC) isoenzymes in multidrug-resistant MCF-7 cells. Functional significance of enhanced expression of PKC alpha, Journal of Biological Chemistry, 268(1), 658-64, January 1993 Abstract
  • Obeid LM, Blobe GC, Karolak LA, Hannun YA, Cloning and characterization of the major promoter of the human protein kinase C beta gene. Regulation by phorbol esters, Journal of Biological Chemistry, 267(29), 20804-10, October 1992 Abstract
  • Khan WA, Blobe GC, Hannun YA, Activation of protein kinase C by oleic acid. Determination and analysis of inhibition by detergent micelles and physiologic membranes: requirement for free oleate, Journal of Biological Chemistry, 267(6), 3605-12, February 1992 Abstract
  • Huber PW, Blobe GC, Hartmann KM, Conformational studies of the nucleic acid binding sites for Xenopus transcription factor IIIA, Journal of Biological Chemistry, 266(5), 3278-86, February 1991 Abstract

Profile Details

Last Verified: 8/14/2009

COS Expertise ID #866272
Reference this profile directly: http://myprofile.cos.com/gblobe