Staff Profile

Prof Rachel Chambers

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Personal Profile

Name: Rachel Chambers Email: r.chambers@ucl.ac.uk
Title: Prof Tel: 020 76796978
Department: Internal Medicine Fax: 020 76796973
Position: Professor of Respiratory Cell and Molecular Biology Address: Centre for Respiratory Research, Rayne Institute, 5 University Street, London, WC1E 6JJ
Research Domain: Basic Life Sciences, Experimental Medicine, Infection Immunology & Inflammation Web Page: Personal Web Page

Profile

Research Description

Our research interests are centred on the elucidation of the cell and molecular mechanisms involved in driving lung injury, inflammation and fibrosis, with a particular emphasis on the role of the coagulation proteinases and their main signalling receptors, the proteinase-activated receptors (PARs). This research is based within the clinical settings of acute lung injury, pulmonary fibrosis and airway remodelling in asthma and COPD.

Current studies in my group are focussed on delineating the signalling pathways and transcriptional programmes by which the major high-affinity thrombin receptor, PAR-1 contributes to lung pathophysiology using genetic and pharmacological approaches in vitro and in vivo. These studies are centred on elucidating the mechanism and signalling pathways by which PAR-1 mediates fibroblast to myofibroblast differentiation during the development of fibrosis and orchestrates the chemokine and cytokine response following acute and chronic lung injury. We are also conducting studies aimed at defining the relevant PAR-1 activation proteinases in these settings using both patient biopsy material and by performing functional studies in in vivo models. PAR-1 antagonists are currently being developed as potent anti-thrombotic agents and pre-clinical studies to evaluate their potential usefulness in the setting of acute lung injury and fibroproliferative lung disease are currently ongoing in our centre.

This work is being carried out by an active and dynamic group of senior scientists (Chris Scotton; Paul Mercer) and clinician scientists at various stages of their academic careers, ranging from PhD student to advanced clinician scientist and is supported by grants obtained from The Wellcome Trust, The Medical Research Council, The British Lung Foundation and The Rosetrees Trust. My groups is alo part of a European Union Framework 7-funded network (eurIPFnet) of respiratory scientists and clinicians engaged in deciphering the natural course and patomechanisms leading to lung fibrosis (http://www.pulmonary-fibrosis.net/).

Research Activities

Molecular pathogenesis of fibroproliferative lung disease

Procoagulant signalling in response to lung injury

Education Description

I lead an active research group of basic scientists and clinicical fellows working towards the degree of PhD. Our research is based within the clinical setting of lung injury, inflammation and fibrosis. Our main focus is to determine the contribution of procoagulant signalling pathways in driving excessive inflammation and remodelling following acute and chronic lung injury.

I am also Postgraduate Tutor for the Division of Medicine. Our Division currently comprises around 150 postgraduate students (basic science students and clinical fellows)registered for the degree of PhD or MD (Res) across a broad range of biomedical disciplines.

UCL Collaborators

Prof David Abraham; Dr Robin Mcanulty; Dr Chris Scotton

External Collaborators

Darryl Knight; Gisli Jenkins

Publications

    2011

    2010

    • Scotton CJ, Chambers RC (2010). Bleomycin revisited: towards a more representative model of IPF?. Am J Physiol Lung Cell Mol Physiol, 299(4), L439 - L441. doi:10.1152/ajplung.00258.2010
    • Maher TM, Evans IC, Bottoms SE, Mercer PF, Thorley AJ, Nicholson AG, Laurent GJ, Tetley TD, Chambers RC, McAnulty RJ (2010). Diminished prostaglandin E2 contributes to the apoptosis paradox in idiopathic pulmonary fibrosis.. American Journal of Respiratory and Critical Care Medicine, 182, 73 - 82. doi:10.1164/rccm.200905-0674OC

    2009

    • Atzori L, Lucatelli M, Scotton CJ, Laurent GJ, Bartalesi B, De Cunto G, Lunghi B, Chambers RC, Lungarella G (2009). Absence of Proteinase Activated Receptor-1 Signaling in Mice Confers Protection from fMLP-induced Goblet Cell Metaplasia.. American Journal of Respiratory Cell and Molecular Biology, , - .
    • Scotton CJ, Krupiczojc MA, Koenigshoff M, Mercer PF, Lee YCG, Kaminski N, Morser J, Post JM, Maher TM, Nicholson AG, Moffatt JD, Laurent GJ, Derian CK, Eickelberg O, Chambers RC (2009). Increased local expression of coagulation factor X contributes to the fibrotic response in human and murine lung injury. Journal of Clinical Investigation, 119(9), 2550 - 2563.
    • Mercer PF, Johns RJ, Scotton CJ, Krupiczojc MA, Howell DCJ, Koenigshoff M, McAnulty RJ, Das A, Thorley AJ, Tetley TD, Eickelberg O, Chambers RC (2009). Pulmonary epithelium is a prominent source of proteinase-activated receptor-1-inducible CCL2 in pulmonary fibrosis. American Journal of Respiratory and Critical Care Medicine, 179(5), 414 - 425.

    2008

    • Maher TM, Evans IC, Bottoms SE, Mercer PF, Thorley AJ, Wells AU, Laurent GJ, Nicholson AG, Tetley TD, Chambers RC, McAnulty RJ (2008). THE ROLE OF COX-2 DERIVED PGE(2) IN MODULATING THE BALANCE OF APOPTOSIS IN THE EPITHELIAL-MESENCHYMAL TROPHIC UNIT: AN IMPORTANT MECHANISM IN THE PATHOGENESIS OF IDIOPATHIC PULMONARY FIBROSIS.
    • Chen D, Carpenter A, Abrahams J, Chambers RC, Lechler RI, McVey JH, Dorling A (2008). Protease-activated receptor 1 activation is necessary for monocyte chemoattractant protein 1-dependent leukocyte recruitment in vivo.. Journal of Experimental Medicine, 205(8), 1739 - 1746. doi:10.1084/jem.20071427
    • Laurent GJ, McAnulty RJ, Hill MR, Chambers RC (2008). Escape from the matrix: multiple mechanisms for fibroblast activation in pulmonary fibrosis. Proc Am Thorac Soc, 5(3), 311 - 315.
    • Krupiczojc MA, Scotton CJ, Chambers RC (2008). Coagulation signalling following tissue injury: Focus on the role of factor Xa. Int J Biochem Cell Biol., 40(6-7), 1228 - 1237. doi:10.1016/j.biocel.2008.02.026
    • Chambers RC (2008). Abnormal wound healing responses in pulmonary fibrosis: focus on coagulation signalling.. Eur Respir Rev, 109, 1 - 9.
    • Chambers RC (2008). Procoagulant signalling mechanisms in lung inflammation and fibrosis: novel opportunities for pharmacological intervention?. Br J Pharmacol, 153(Suppl 1), S367 - S378. doi:10.1038/sj.bjp.0707603
    • Deng X, Mercer PF, Scotton CJ, Gilchrist A, Chambers RC (2008). Thrombin induces fibroblast CCL2/JE production and release via coupling of PAR1 to Gαq and cooperation between ERK1/2 and Rho kinase signaling pathways.. Molecular Biology of the Cell, 19(6), 2520 - 2533.

    2007

    • Maher TM, Bottoms SE, Mercer PF, Scotton CJ, Thorley A, Wells AU, Nicholson AG, Laurent GJ, Tetley TD, Chambers RC, Mcanulty RJ (2007). Differential modulation of lung fibroblast and alveolar epithelial cell apoptosis by cyclo-oxygenase (COX)-2 and prostaglandin E-2 is an important mechanism in the pathogenesis of idiopathic pulmonary fibrosis.
    • Laurent GJ, Chambers RC, Hill MR, McAnulty R (2007). Regulation of matrix turnover: fibroblasts, forces, factors and fibrosis. Biochemical Society Transactions, 35(4), 647 - 651.
    • Scotton CJ, Chambers RC (2007). Molecular targets in pulmonary fibrosis: the myofibroblast in focus.. Chest, 132, 1311 - 1321. doi:10.1378/chest.06-2568
    • Mercer PF, Moffatt JD, Scotton CJ, Derian CK, Chambers RC (2007). Par1 signalling in lipopolysaccharide-induced acute lung injury.
    • Mercer PF, Deng XC, R C (2007). Signaling pathways involved in proteinase-activated receptor1-induced proinflammatory and profibrotic mediator release following lung injury.. Ann NY Acad Sci, 1096, 86 - 88. doi:10.1196/annals.1397.073
    • Kallis YN, Scotton CJ, Goldin RD, Russo FP, Chambers RC, Thomas HC, Forbes SJ (2007). PAR-1 knockout bone marrow stem cells can confer an anti-fibrotic phenotype to the injured liver.

    2006

    • Howell DCJ, Falzon M, Bilbe N, Bottoms SE, Laurent GJ, Chambers RC, Bellingan GJ (2006). Pulmonary fibrosis is an early feature of acute lung injury/acute respiratory distress syndrome.
    • Ku CH, Johnson PH, Batten P, Sarathchandra P, Chambers RC, Taylor PM, Yacoub MH, Chester AH (2006). Collagen synthesis by mesenchymal stem cells and aortic valve interstitial cells in response to mechanical stretch.. Cardiovascular Research, 71(3), 548 - 556. doi:10.1016/j.cardiores.2006.03.022
    • Chambers RC (2006). Thrombin. In Shapiro SD, Laurent GJ (Ed.), Encyclopaedia of Respiratory Medicine (pp. - ). : Elsevier.
    • Scotton CJ, Krupiczojc M, Johns RH, Lee YCG, Koenigshoff M, Eickelberg O, Kaminski N, Laurent GJ, Chambers RC (2006). The coagulation cascade in fibrotic lung disease progression: local expression of factor X is increased in the injured and fibrotic lung.
    • Wilson NA, Worku ML, Moffatt JD, Sasikumar P, Davies RJO, Laurent GJ, Chambers RC, Lee YCG (2006). Activation of proteinase activated receptor-1 on mesothelial cells induces activation of transforming growth factor-beta via upregulation of thrombospondin-1.
    • Moffatt JD, Wilson NA, Worku ML, Sasikumar P, Laurent GJ, Chambers RC, Lee YCG (2006). Talc induces release of transforming growth factor-beta from mesothelial cells in vitro and serosal adhesion formation in vivo.
    • Jenkins RG, Su X, Su G, Scotton CJ, Camerer E, Laurent GJ, Davis GE, Chambers RC, Matthay MA, Sheppard D (2006). Ligation of protease-activated receptor 1 enhances alpha(v)beta(6) integrin-dependent TGF-beta activation and promotes acute lung injury. Journal of Clinical Investigation, 116(6), 1606 - 1614.
    • Chambers RC (2006). Proteinase-activated receptors. In Shapiro SD, Laurent GJ (Ed.), Encyclopaedia of Respiratory Medicine (pp. - ). : Elsevier.

    2005

    • Deng XL, Mercer PF, Laurent GJ, Chambers RC (2005). Identification of PAR1-G protein signaling pathways involved in thrombin induced CCL2 release.
    • Johns RH, Scotton CJ, Laurent GJ, Chambers RC (2005). PAR1 signaling in lung epithelial cells induces the expression of CCL2/MCP-1 and CTGF.
    • Krupiczojc MA, Scotton CJ, Laurent GJ, Chambers RC (2005). Activation of PAR1 by FXa induces fibroblast to myofibroblast differentiation.
    • Gunnell A, Moffatt JD, Wilson NA, Johns RH, Sasikumar P, Yu WC, Laurent GJ, Chambers RC, Lee YCG (2005). Thrombin induced release of active transforming growth factor-beta from mesothelial cell: A potential mechanism of adhesion formation in pleural infection.
    • Lee YC, Knight DA, Lane KB, Cheng DS, Koay MA, Teixeira LR, Nesbitt JC, Chambers RC, Thompson PJ, Light RW (2005). Activation of proteinase-activated receptor-2 in mesothelial cells induces pleural inflammation.. American Journal of Physiology - Lung Cellular and Molecular Physiology, 288(4), 734 - 740. doi:10.1152/ajplung.00173.2004
    • Blanc-Brude O, Archer F, Leoni P, Derian C, Bolsover SR, Laurent GJ, Chambers RC (2005). Factor Xa stimulates fibroblast procollagen production, proliferation and calcium signaling via PAR1 activation. Experimental Cell Research, 304(1), 16 - 27.
    • Howell DC, Johns RH, Lasky JA, Shan B, Scotton CJ, Laurent GJ, Chambers RC (2005). Absence of proteinase-activated receptor-1 signaling affords protection from bleomycin-induced lung inflammation and fibrosis.. American Journal Of Pathology, 166(5), 1353 - 1365..

    2004

    • Johns RH, Howell DCJ, Laurent GJ, Chambers RC (2004). Absence of proteinase activated receptor-1 signalling affords protection from experimentally induced lung inflammation and fibrosis.
    • Marshall RP, Gohlke P, Chambers RC, Howell DC, Bottoms SE, Unger T, McAnulty RJ, Laurent GJ (2004). Angiotensin II and the fibroproliferative response to acute lung injury. American Journal of Physiology - Lung Cellular and Molecular Physiology, 286(1), L156 - L164.

    2003

    • Chambers RC (2003). Role of coagulation cascade proteases in lung repair and fibrosis. European Respiratory Journal - Supplement, 44, 33s - 35s.
    • Chambers RC (2003). Proteinase-activated receptors and the pathophysiology of pulmonary fibrosis.. Drug Development Research, 60, 29 - 35.
    • Chambers RC, Leoni P, Kaminski N, Laurent GJ, Heller RA (2003). Global expression profiling of fibroblast responses to transforming growth factor-beta1 reveals the induction of inhibitor of differentiation-1 and provides evidence of smooth muscle cell phenotypic switching. American Journal of Pathology, 162(2), 533 - 546.

    2002

    • Chambers RC (2002). Gene expression profiling: good housekeeping and a clean message.. Thorax, 57, 754 - 756.
    • Simler NR, Howell DC, Marshall RP, Goldsack NR, Hasleton PS, Laurent GJ, Chambers RC, Egan JJ (2002). The rapamycin analogue SDZ RAD attenuates bleomycin-induced pulmonary fibrosis in rats. European Respiratory Journal, 19(6), 1124 - 1127.
    • Lindahl GE, Chambers RC, Papakrivopoulou J, Dawson SJ, Jacobsen MC, Bishop JE, Laurent GJ (2002). Activation of fibroblast procollagen alpha 1 (I) transcription by mechanical strain is transforming growth factor-beta-dependent and involves increased binding of CCAAT-binding factor (CBF/NF-Y) at the proximal promoter. Journal of Biological Chemistry, 277(8), 6153 - 6161. doi:10.1074/jbc.M108966200
    • Dunsmore SD, Chambers RC, Laurent GJ (2002). Matrix Proteins.. In Gibson J, Geddes D, Costabel U, Sterk P, Corrin B (Ed.), Respiratory Medicine 3rd Edition (pp. 82 - 92). : Harcourt Health Sciences.
    • Howell DC, Laurent GJ, Chambers RC (2002). Role of thrombin and its major signalling receptor, protease activated receptor-1 in pulmonary fibrosis.. Biochem Soc Trans, 30(2), 211 - 216.
    • Howell DC, Laurent GJ, Chambers RC (2002). Role of thrombin and its major cellular receptor, protease-activated receptor-1, in pulmonary fibrosis. Biochemical Society Transactions, 30(2), 211 - 216.
    • Chambers RC, Laurent GJ (2002). Coagulation cascade proteases and tissue fibrosis. Biochemical Society Transactions, 30(2), 194 - 200.

    2001

    • Dabbagh K, Laurent GJ, Shock A, Leoni P, Papakrivopoulou J, Chambers RC (2001). Alpha-1-antitrypsin stimulates fibroblast proliferation and procollagen production and activates classical MAP kinase signalling pathways. Journal of Cellular Physiology, 186(1), 73 - 81.
    • Howell DCJ, Dunscombe AO, Laurent GJ, Chambers RC (2001). Primary rat lung fibroblasts express functional protease activated receptor-1 (PAR-1) and respond to the profibrotic effects of thrombin. THORAX, 56, 5 - 5.
    • Howell DC, Goldsack NR, Marshall RP, McAnulty RJ, Starke R, Purdy G, Laurent GJ, Chambers RC (2001). Direct thrombin inhibition reduces lung collagen, accumulation, and connective tissue growth factor mRNA levels in bleomycin-induced pulmonary fibrosis. American Journal Of Pathology, 159(4), 1383 - 1395.
    • Blanc-Brude OP, Chambers RC, Leoni P, Dik WA, Laurent GJ (2001). Factor Xa is a fibroblast mitogen via binding to effector-cell protease receptor-1 and autocrine release of PDGF. American Journal of Physiology - Cell Physiology, 281(2), C681 - C689.

    2000

    • Howell DCJ, Laurent GJ, Considine MG, Chambers RC (2000). Abrogation of bleomycin-induced lung collagen accumulation by direct thrombin inhibition, is preceded by a reduction in alpha(2)(I) procollagen and CTGF mRNA levels. THORAX, 55, A14 - A14.
    • Chambers RC, Leoni P, Blanc-Brude OP, Wembridge DE, Laurent GJ (2000). Thrombin is a potent inducer of connective tissue growth factor production via proteolytic activation of protease-activated receptor-1. Journal of Biological Chemistry, 275(45), 35584 - 35591.
    • Chambers RC (2000). Role of Thrombin in Acute Lung Injury.. In Bellingan GJ, Laurent GJ (Ed.), Mechanisms of Acute Lung Injury (pp. 115 - 128). : IOS Press.

    1999

    • Laurent GJ, McAnulty RJ, Chambers RC, Keerthisingam CB (1999). Regulation of procollagen genes. From forces to factors.. Journal of Chemical Sciences, 111(1), 291 - 299. doi:10.1007/BF02869918
    • Chambers RC, Allard J, Lock C, Van Wart H, Laurent GJ, Wembridge DE, Heller RA (1999). Profiling changes in fibroblast gene expression induced by TGF beta(1) using oligonucleotide gene-chips. AM J RESP CRIT CARE, 159(3), A928 - A928.
    • Howell DCJ, Goldsack NR, Marshall RP, Gray AJ, McAnulty RJ, Laurent GJ, Chambers RC (1999). Direct thrombin inhibition attenuates bleomycin-induced pulmonary fibrosis.
    • Simler NR, Howell DCJ, Marshall RP, Laurent GJ, Chambers RC, Egan JJ (1999). The rapamycin analogue SDZ RAD attenuates bleomycin-induced pulmonary fibrosis in rats. THORAX, 54, A15 - A15.
    • Jenkins RG, Hart SL, Chambers RC, Herrick SE, Kinnon C, Laurent GJ, McAnulty RJ (1999). Enhanced gene delivery to the lung using a novel integrin mediated vector.

    1998

    • Dabbagh K, Laurent GJ, McAnulty RJ, Chambers RC (1998). Thrombin stimulates smooth muscle cell procollagen synthesis and mRNA levels via a PAR-1 mediated mechanism. Thrombosis and Haemostasis, 79(2), 405 - 409.
    • Goldsack NR, Chambers RC, Dabbagh K L, G J (1998). Molecules in Focus: Thrombin. Int J Biochem Cell Biol., 30.(6), 641 - 646. doi:10.1016/S1357-2725(98)00011-9
    • Goldsack NR, Chambers RC, Dabbagh K, Laurent GJ (1998). Thrombin. INT J BIOCHEM CELL BIOL, 30(6), 641 - 646.
    • Chambers RC, Laurent GJ, Westergren T (1998). Cadmium inhibits proteoglycan and procollagen production by cultured human lung fibroblasts. AM J RESPIR CELL MOL BIOL, 19(3), 498 - 506.
    • Chambers RC, Dabbagh K, McAnulty RJ, Gray AJ, Blanc-Brude OP, Laurent GJ (1998). Thrombin stimulates fibroblast procollagen production via proteolytic activation of protease-activated receptor 1. Biochemical Journal, 333(Pt 1), 121 - 127.
    • Dabbagh K, Chambers RC, Laurent GJ (1998). From clot to collagen: coagulation peptides in interstitial lung disease.. Eur Respir J, 11(5), 1002 - 1005.
    • Mutsaers SE, Foster ML, Chambers RC, Laurent GJ, McAnulty RJ (1998). Increased endothelin-1 and its localization during the development of bleomycin-induced pulmonary fibrosis in rats. American Journal of Respiratory Cell and Molecular Biology, 18(5), 611 - 619.

    1997

    • Chambers RC, Laurent GJ (1997). The Lung.. In Comper WD (Ed.), Structure and Function of the Extracellular Matrix (pp. 378 - 409). : Harwood Academic Publishers.
    • Chambers RC, Laurent GJ (1997). Collagens.. In Crystal RG, West JB, Weibel ER, Barnes PJ (Ed.), The Lung: Scientific Foundations (pp. 709 - 727). : Lippincott-Raven.
    • Chambers RC, Laurent GJ (1997). Putative Role for Cadmium in the Pathogenesis of Emphysema.. In Mohr U (Ed.), Correlations between in vitro and in vivo Investigations in Inhalation Toxicology (pp. 365 - 379). : ILSI Press.

    1995

    • McAnulty RJ, Chambers RC, Laurent GJ (1995). Regulation of fibroblast procollagen production: Transforming growth factor-β1 induces prostaglandin E2 but not procollagen synthesis via a pertussis toxin sensitive G-protein.. Biochemical Journal, 307, 63 - 68.
    • Hernandez Rodriguez NA, Cambrey AD, Harrison NK, Chambers RC, Gray AJ, Southcott AM, duBois AM, Black CM, Scully MF, McAnulty RJ, Laurent GJ (1995). Role of thrombin in pulmonary fibrosis.. The Lancet, 346, 1071 - 1073.
    • CHAMBERS RC, DABBAGH K, HERNANDEZRODRIGUEZ N, LAURENT GJ (1995). THROMBIN STIMULATES PROCOLLAGEN PRODUCTION AND GENE-EXPRESSION BY CULTURED HUMAN FIBROBLASTS. MOL BIOL CELL, 6, 258 - 258.
    • Winlove CP, Bishop JE, Chambers RC, Laurent GJ (1995). The structure and function of extracellular matrix in the pulmonary vasculature.. In Bishop JE, Reevs JT, Laurent GJ (Ed.), The Pulmonary Vasculature (pp. 21 - 46). : Portland Press.

    1994

    • Chambers RC, McAnulty RJ, Shock A, Campa JS, NewmanTaylor AJ, Laurent GJ (1994). Cadmium selectively inhibits fibroblast procollagen production and proliferation.. American Journal of Physiology - Lung Cellular and Molecular Physiology, 267, 300 - 308.

    1991

    • Shock A, Rabe KF, Dent G, Chambers RC, Gray AJ, Chung KF, Barnes PJ, Laurent GJ (1991). Eosinophils adhere to and stimulate replication of lung fibroblasts in vitro.. Clinical and Experimental Neurology, 86, 185 - 190.

    • Naldini A, Johns RH, Adinghi C, Carro F, Chambers RC (). PAR-1 influences multiple cytokine networks following bleomycin-induced lung injury.. American Journal of Physiology - Lung Cellular and Molecular Physiology, , - .
    • Kallis YN, Scotton CJ, Goldin RD, Thomas HC, Alison MR, Wright NA, Iredale JP, Chambers RC, Forbes SJ (). The bone marrow can modulate liver fibrosis via proteinase-activated receptor-1 signalling on macrophages.. Gut, , - .