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BRIGSTOCK LABORATORY We are studying the role of connective tissue growth factor (CTGF) in fibrotic diseases, which are characterized by excessive production and deposition of insoluble collagen matrix, resulting in loss of tissue structure and organ dysfunction. Our main research efforts are currently focussed on liver and pancreatic fibrosis but we have collaborative efforts that focus on other organ systems such as the lung, intestine, heart and skin. Using molecular, cellular and biochemical approches, both in vitro and in vivo, our goals are to understand the mechanisms by which CTGF stimulates collagen production by fibrogenic cells types. In this manner, we will determine the therapeutic value of targetting pathways of CTGF biosynthesis or action to treat a variety of fibrotic disorders.
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| Education |
| 1991 |
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Post-Doc |
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Cell Biology |
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Harvard Medical School, Boston MA |
| 1988 |
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Ph.D. |
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Biochemistry |
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Cambridge University, Cambridge, England |
| Professional Experience |
| 1998- Pres |
Faculty Member - Hormones and Cancer Program, Arthur James Cancer Center, The Ohio State University |
| 1997- Pres |
Associate Professor of Medical Biochemistry, The Ohio State University College of Medicine |
| 1997- Pres |
Associate Professor of Surgery, Department of Surgery, Division of Pediatric Surgery, The Ohio State University College of Medicine |
| 1997- Pres |
Faculty Member - Ohio State University Biochemistry Program |
| 1993- Pres |
Faculty Member - Molecular, Cellular and Developmental Biology Program, The Ohio State University |
| 1991- Pres |
Director, Pediatric Surgery Research Laboratory, Ohio State University and Children's Hospital, Columbus, OH |
| 1994- 1998 |
Faculty Member - Pediatric Oncology Program, Arthur James Cancer Center, Ohio State University |
| 1992- 1997 |
Assistant Professor of Medical Biochemistry, The Ohio State University College of Medicine |
| 1991- 1997 |
Assistant Professor of Surgery, Department of Surgery, Division of Pediatric Surgery, The Ohio State University College of Medicine |
| 1988- 1991 |
Research Fellow, Department of Surgery, Harvard Medical School and Children's Hospital, Boston MA |
BRIGSTOCK LABORATORY STAFF
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Principal Investigator:
David R. Brigstock, Ph.D.
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| Selected Publications |
| Zhou Y, Brigstock D, Besner GE (2009).Heparin-binding EGF-like growth factor is a potent dilator of terminal mesenteric arterioles. Microvasc Res. 2009 78 78-85 |
| Charrier A and Brigstock D (2009) Connective tissue growth factor localizes to activated pancreatic stellate cells in a model of ethanol-induced pancreatic fibrosis. Annual Meeting of ASCB, San Diego CA Dec 7-11 |
| Li C, Leask A, Brigstock D (2009) Ethanol-mediated connective tissue growth factor (CTGF) mRNA expression and promoter activity in human LX-2 hepatic stellate cells. Annual Meeting of AASLD, Boston MA Oct 31 - Nov3 |
| Huang G and Brigstock DR (2009) Differential modulation of integrins gene expression by connective tissue growth factor in early and activated primary culture hepatic stellate cells. Digestive Disease Week, Chicago, May 30-June 4 |
| Huang G and Brigstock DR (2009) Integrin α5β1 is a CTGF receptor on early primary culture hepatic stellate cells and interacts with fibronectin and heparan sulfate proteglycans to regulate CTGF function. Digestive Disease Week, Chicago, May 30-June 4 |
| Charrier A and Brigstock DR (2009) A model of ethanol-induced pancreatic fibrosis in mice. Research Day, The Research Institute at Nationwide Children’s Hospital, Columbus May 15, 2009 |
| Lawrencia, C., Brigstock DR (2009) Resolution of experimental liver fibrosis in mice by targeted delivery of connective tissue growth factor siRNA. Experimental Biology 2009. New Orleans April 18-22. |
| Brigstock DR (2009) Connective tissue growth factor (CCN2, CTGF) and organ fibrosis: Lessons from transgenic animals. J. Cell Comm. Signal http://dx.doi.org/1007/s12079-009-0071-5 |
| Gao R and Brigstock DR (2009) Connective tissue growth factor hammerhead ribozyme attenuates human hepatic stellate cell function. World J Gastroenterology 15 3807-3813 |
| Tong Z, Chen R, Kemper S, Perbal B, and Brigstock DR (2009) Susceptibility to liver fibrosis in mice expressing a connective tissue growth factor transgene in hepatocytes Hepatology 50 939-947 |
| Lawrenica C, Charrier A, Huang G and Brigstock DR (2009) Ethanol-mediated expression of connective tissue growth factor (CCN2) in mouse pancreatic stellate cells Growth Factors 27 91-99 |
| Crawford LA, Guney MA, Oh YA, Deyoung RA, Valenzuela DM, Murphy AJ, Yancopoulos GD, Lyons KM, Brigstock DR, Economides A, Gannon M (2009) Connective tissue growth factor (CTGF) inactivation leads to defects in islet cell lineage allocation and ? cell proliferation during embryogenesis. Mol Endocrinol 23:324-36. |
| Liu, J, Xu W, Sun T, Wang F, Puscheck EE, Brigstock D, Wang Q, Davis R, Rappolee DR (2009) Hyperosmolar stress induces global mRNA responses in placental trophoblast stem cells that emulate early post-implantation differentiation. Placenta 30 66-73 |
| Wang J, Leclercq, Brymore JM, Ramezani-Mogadam M, London RM, Brigstock DR, George J (2009). Kupffer cells mediate leptin-induced liver fibrosis Gastroenterology 137 713-723 |
| Brigstock DR (2009) Strategies for blocking the fibrogenic actions of connective tissue growth factor (CCN2): From pharmacological inhibition in vitro to targeted siRNA therapy in vivo. J. Cell Comm Signal 3 5-18 |
| Leask A, Chen S, Pala D, and Brigstock DR (2008) Regulation of CCN2 expression and promoter activity in activated hepatic stellate cells. J. Cell Comm. 2 49-56 |
| Dean RA, Butler GS, Hamma-Kourbali Y, Delbe J, Brigstock DR, Courty J, Overall CM (2007) Identification of candidate angiogenic inhibitors processed by MMP-2 in cell based proteomic screens: Disruption of VEGF / HARP (Pleiotrophin) and VEGF / CTGF angiogenic inhibitory complexes by MMP-2 Proteolysis/ Mol Biol Cell 27 8454-8465 |
| Boag, JM, Beesley AH, Firth, MJ, Freitas, JR, Ford J, de Klerk NH, Brigstock DR, Kees UR (2007) High expression of Connective Tissue Growth Factor in pre-B Acute Lymphoblastic Leukaemia British Journal of Haematology 138: 740-748. |
| Baran CP, Opalek JM, McMaken S, Newland CA, O’Brien JM, Hunter MG, Bringardner BD, Monick MM, Brigstock DR, Stromberg PC, Hunninghake GW and Marsh CB (2007) Important roles for M-CSF, CCL2 and mononuclear phagocytes in the pathogenesis of pulmonary fibrosis. Am J Respir Crit Care Med 176 78-89 |
| Cooker L, Peterson D, Rambow J, Riser M, Riser R, Najmabadi F, Brigstock D, and Riser B. (2007) TNF-alpha, but not IFN-gamma, Regulates CCN2 (CTGF), Collagen Type I, and proliferation in mesangial cells: Possible roles in the progression of renal fibrosis. Am J Physiol Renal Physiol. 293 F157-65 |
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