Nationwide Children's Hospital
700 Children's Drive
Columbus, OH 43205-2664
614-355-2824

Research interests: Biology of connective tissue growth factor

Research center: Center for Clinical and Translational Research

Areas of interest: We are studying the role of connective tissue growth factor (CTGF) in fibrotic diseases, which is 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 focused 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 approaches, 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 targeting pathways of CTGF biosynthesis or action to treat a variety of fibrotic disorders.

Education:

1984 BS: Brunel University, West London, United Kingdom
1988 PhD: Cambridge University, Cambridge, United Kingdom
Specialty Training: Harvard University, Cambridge, MA

Nationwide Children's bio


Books, Articles and Published Papers

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 β cell proliferation during embryogenesis. Mol Endocrinol 23:324-36

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

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

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

Gao R and Brigstock DR (2009) Connective tissue growth factor hammerhead ribozyme attenuates human hepatic stellate cell function. World J Gastroenterology 15 3807-3813

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

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

Tong Z, Brigstock, D.R. (2006) Intrinsic biological activity of the thrombospondin structural homology repeat in connective tissue growth factor J. Endocrinol 188 R1-R8

Gao, R. and Brigstock, D.R. (2006) A novel integrin ?5?1–binding domain in module 4 of connective tissue growth factor promotes adhesion and migration of activated pancreatic stellate cells. Gut 55 856-862

Gao R and Brigstock DR (2005) Connective tissue growth factor (CCN2) in rat pancreatic stellate cell function: Integrin ?5?1 as a novel CCN2 receptor. Gastroenterology 129 2019-2030

Gao R, Ball DK, Perbal B, Brigstock DR (2004) Connective tissue growth factor (CCN2) induces c-fos gene activation and cell proliferation through p44/42 MAP kinase (ERK1/2) in primary rat hepatic stellate cells J. Hepatol 40 431-438

Gao R., Brigstock DR (2004) Connective tissue growth factor (CCN2) induces adhesion of rat activated hepatic stellate cells by binding of its carboxyl-terminal domain to integrin ?v?3 and heparan sulfate proteoglycans. J Biol Chem 279 8848-8855

Ball, D.K., Moussad, E.E-D.A., Rageh, M.A.E., Kemper, S.A, Brigstock, D.R. (2003) Establishment of a recombinant expression system for connective tissue growth factor (CTGF) that models CTGF processing in utero. Reproduction 125 271-284

Wang JF, Olson ME, Ball DK, Brigstock DR, Wright JB, Hart DA (2003). Recombinant connective tissue growth factor modulates porcine skin fibroblast gene expression.Wound Repair Regen 11 220-229

Gao R, Brigstock DR (2003) Low-density lipoprotein receptor-related protein is a heparin-dependent adhesion receptor for connective tissue growth factor (CTGF) in rat activated hepatic stellate cells. Hepatol Res 27 214-220

Ball DK, Wilson AW, Kemper SA, Brigstock DR (2003). The heparin-binding 10kDa fragment of connective tissue growth factor (CTGF) containing module 4 alone stimulates cell adhesion. J Endocrinol 176 R1-R7

di Mola FF, Friess H, Riesle E, Koliopanos A, Buchler P., Zhu Z, Brigstock DR, Korc M, Buchler MW (2002) Connective tissue growth factor (CTGF) is involved in pancreatic repair and tissue remodeling in human and rat acute necrotizing pancreatitis. Annals Surgery 235 60-67

Williams, E.J., Gaca, M.D.A., Brigstock, D.R., Arthur, M.J.P, and Benyon, R.C. (2000) Increased expression of connective tissue growth factor in fibrotic human liver and in activated hepatic stellate cells. J. Hepatology 32 754-761

Brigstock, D.R., Steffen, C.L. Kim, G.Y., Vegunta, R.K. Diehl, J.R. and Harding P.A. (1997) Purification and characterization of novel heparin-binding growth factors in uterine secretory fluids: Identification as heparin-regulated 10,000-Mr forms of connective tissue growth factor. J. Biol. Chem.272 20275-20282

Peer Reviewed Journal Articles

Gao R; Brigstock DR, "Connective tissue growth factor (CCN2) induces adhesion of rat activated hepatic stellate cells by binding of its C-terminal domain to integrin alpha(v)beta(3) and heparan sulfate proteoglycan.". The Journal Of Biological Chemistry. Vol. 279, no. 10: 8848. 2004

Rachfal AW; Luquette MH; Brigstock DR, "Expression of connective tissue growth factor (CCN2) in desmoplastic small round cell tumour.". Journal Of Clinical Pathology. Vol. 57, no. 4: 422. 2004

Rachfal AW; Brigstock DR, "Structural and functional properties of CCN proteins.". Vitamins And Hormones. Vol. 70, 69. 2005

Köninger J; di Mola FF; Di Sebastiano P; Gardini A; Brigstock DR; Innocenti P; Büchler MW; Friess H, "Transforming growth factor-beta pathway is activated in cholecystolithiasis.". Langenbeck's Archives Of Surgery / Deutsche Gesellschaft Für Chirurgie. Vol. 390, no. 1: 21. 2005

Cicha I; Yilmaz A; Klein M; Raithel D; Brigstock DR; Daniel WG; Goppelt-Struebe M; Garlichs CD, "Connective tissue growth factor is overexpressed in complicated atherosclerotic plaques and induces mononuclear cell chemotaxis in vitro.". Arteriosclerosis, Thrombosis, And Vascular Biology. Vol. 25, no. 5: 1008. 2005

Brigstock D; Lau L; Perbal B, "Report and abstracts of the 3rd International Workshop on the CCN Family of Genes. St Malo, France, 20-23 October 2004.". Journal Of Clinical Pathology. Vol. 58, no. 5: 463. 2005

Gao R; Brigstock DR, "Connective tissue growth factor (CCN2) in rat pancreatic stellate cell function: integrin alpha5beta1 as a novel CCN2 receptor.". Gastroenterology. Vol. 129, no. 3: 1019. 2005

Gao R; Brigstock DR, "Activation of nuclear factor kappa B (NF-kappaB) by connective tissue growth factor (CCN2) is involved in sustaining the survival of primary rat hepatic stellate cells.". Cell Communication And Signaling: CCS. Vol. 3, 14. 2005

Tong ZY; Brigstock DR, "Intrinsic biological activity of the thrombospondin structural homology repeat in connective tissue growth factor.". The Journal Of Endocrinology. Vol. 188, no. 3: R1. 2006

Csencsits K; Wood SC; Lu G; Faust SM; Brigstock D; Eichwald EJ; Orosz CG; Bishop DK, "Transforming growth factor beta-induced connective tissue growth factor and chronic allograft rejection.". American Journal of Transplantation: Official Journal of The American Society of Transplantation and The American Society of Transplant Surgeons. Vol. 6, no. 5 Pt 1: 959. 2006

Gao R; Brigstock DR, "A novel integrin alpha5beta1 binding domain in module 4 of connective tissue growth factor (CCN2/CTGF) promotes adhesion and migration of activated pancreatic stellate cells.". Gut. Vol. 55, no. 6: 856. 2006

Cooker LA; Peterson D; Rambow J; Riser ML; Riser RE; Najmabadi F; Brigstock D; Riser BL, "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.". American Journal Of Physiology. Renal Physiology. Vol. 293, no. 1: F157. 2007

Baran CP; Opalek JM; McMaken S; Newland CA; O'Brien JM Jr; Hunter MG; Bringardner BD; Monick MM; Brigstock DR; Stromberg PC; Hunninghake GW; Marsh CB, "Important roles for macrophage colony-stimulating factor, CC chemokine ligand 2, and mononuclear phagocytes in the pathogenesis of pulmonary fibrosis.". American Journal Of Respiratory and Critical Care Medicine. Vol. 176, no. 1: 78. 2007

Boag JM; Beesley AH; Firth MJ; Freitas JR; Ford J; Brigstock DR; de Klerk NH; Kees UR, "High expression of connective tissue growth factor in pre-B acute lymphoblastic leukaemia.". British Journal of Haematology. Vol. 138, no. 6: 740. 2007

Dean RA; Butler GS; Hamma-Kourbali Y; Delbé J; Brigstock DR; Courty J; Overall CM, "Identification of candidate angiogenic inhibitors processed by matrix metalloproteinase 2 (MMP-2) in cell-based proteomic screens: disruption of vascular endothelial growth factor (VEGF)/heparin affin regulatory peptide (pleiotrophin) and VEGF/Connective tissue growth factor angiogenic inhibitory complexes by MMP-2 proteolysis.". Molecular And Cellular Biology. Vol. 27, no. 24: 8454. 2007

Leask A, Chen S, Pala D, Brigstock DR., "Regulation of CCN2 mRNA expression and promoter activity in activated hepatic stellate cells.". J Cell Commun Signal. Vol. 2, no. 1-2: 49-56. 2008

Liu J; Xu W; Sun T; Wang F; Puscheck E; Brigstock D; Wang QT; Davis R; Rappolee DA, "Hyperosmolar stress induces global mRNA responses in placental trophoblast stem cells that emulate early post-implantation differentiation.". Placenta. Vol. 30, no. 1: 66. 2009

Crawford LA; Guney MA; Oh YA; Deyoung RA; Valenzuela DM; Murphy AJ; Yancopoulos GD; Lyons KM; Brigstock DR; Economides A; Gannon M, "Connective tissue growth factor (CTGF) inactivation leads to defects in islet cell lineage allocation and beta-cell proliferation during embryogenesis.". Molecular Endocrinology (Baltimore, Md.). Vol. 23, no. 3: 324. 2009

Brigstock DR, "Strategies for blocking the fibrogenic actions of connective tissue growth factor (CCN2): From pharmacological inhibition in vitro to targeted siRNA therapy in vivo.". Journal of Cell Communication and Signaling. Vol. 3, no. 1: 5. 2009

Lawrencia C; Charrier A; Huang G; Brigstock DR, "Ethanol-mediated expression of connective tissue growth factor (CCN2) in mouse pancreatic stellate cells.". Growth Factors (Chur, Switzerland). Vol. 27, no. 2: 91. 2009

Zhou Y; Brigstock D; Besner GE, "Heparin-binding EGF-like growth factor is a potent dilator of terminal mesenteric arterioles.". Microvascular Research. Vol. 78, no. 1: 78. 2009

Wang J; Leclercq I; Brymora JM; Xu N; Ramezani-Moghadam M; London RM; Brigstock D; George J, "Kupffer cells mediate leptin-induced liver fibrosis.". Gastroenterology. Vol. 137, no. 2: 713. 2009

Gao RP; Brigstock DR, "Connective tissue growth factor hammerhead ribozyme attenuates human hepatic stellate cell function.". World Journal of Gastroenterology: WJG. Vol. 15, no. 30: 3807. 2009

Tong Z; Chen R; Alt DS; Kemper S; Perbal B; Brigstock DR, "Susceptibility to liver fibrosis in mice expressing a connective tissue growth factor transgene in hepatocytes.". Hepatology (Baltimore, Md.). Vol. 50, no. 3: 939. 2009

Brigstock DR, "Connective tissue growth factor (CCN2, CTGF) and organ fibrosis: lessons from transgenic animals.". Journal Of Cell Communication And Signaling. Vol. 4, no. 1: 1. 2010

Charrier AL; Brigstock DR, "Connective tissue growth factor production by activated pancreatic stellate cells in mouse alcoholic chronic pancreatitis.". Laboratory Investigation; A Journal Of Technical Methods And Pathology. Vol. 90, no. 8: 1179. 2010