Dr Jill Norman

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Name: Jill Norman Email: j.norman@ucl.ac.uk
Title: Dr Tel: 0044 20 7794 0500
Department: Internal Medicine Fax: 0044 20 7317 8591
Position: Reader in Nephrology Address: Centre for Nephrology, 2nd Floor, University College Medical School, Royal Free Campus, London, NW3 2PF
Research Domain: Experimental Medicine, Personalised Medicine Web Page: Personal Web Page

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Research Description

The aim of this work is to investigate the cellular and molecular mechanisms underlying the pathogenesis of progressive fibrosis of the kidney, which is the cardinal feature of chronic kidney disease (CKD). Although many progressive diseases are glomerular in origin, it is tubulointerstitial involvement that best predicts progression. In understanding how glomerular injury is transmitted to the tubulointerstitium, our group has suggested an important role for hypoxia; an idea formalised as the Chronic Hypoxia Hypothesis (Fine et al Kidney Int, 53 Suppl 65:S74-S78, 1998). In support of this hypothesis, in vivo, in a model of progressive renal disease, tissue hypoxia precedes renal scarring and in vitro studies have demonstrated that hypoxia (1% O2) can promote a fibrogenic phenotype in tubular epithelial cells and renal fibroblasts. Current studies are centred on understanding of the role of hypoxia in the pathogenesis of renal fibrosis. Specific areas of investigation include the mechanisms of hypoxic regulation of expression of fibrogenic genes; the control of fibroblast to myofibroblast differentiation; and the role of fibroblast-endothelial cell and fibroblast-epithelial cell interactions in the pathogenesis of fibrosis.

Research Activities

Cellular and molecular mechanisms of fibrosis

Mechanisms of tissue repair, scarring and fibrosis

Education Description

UCL Collaborators

Prof David Abraham; Prof Christopher Denton; Prof Jim Owen; Miss Janice Tsui; Dr Marilena Loizidou

External Collaborators

Karen Lyons; Benoit De Crombrugghe; James Bonner; Kristofer Rubin; Thomas Kreig; Oliver Distler; Andrew Leask

Publications

    2013

    • Donovan J, Shiwen X, Norman J, Abraham D (2013). Platelet-derived growth factor alpha and beta receptors have overlapping functional activities towards fibroblasts.. Fibrogenesis Tissue Repair, 6(1), 10 - . doi:10.1186/1755-1536-6-10
    • Sonnylal S, Shiwen X, Jones H, Tam A, Sreeram VR, Ponticos M, Norman JT, Agrawal P, Abraham DJ, de Crombrugge B (2013). Connective tissue growth factor causes EMT-like cell fate changes in vivo and in vitro. Journal of Cell Science, , - .
    • Tam A, Majumdar S, Leask A, de Crombrugghe B, Norman J, Abraham D (2013). CCN2-induced EMT in lung fibrosis.
    • Fish RS, Klootwijk E, Tam FW, Kleta R, Wheeler DC, Unwin RJ, Norman J (2013). ATP and arterial calcification. European Journal of Clinical Investigation, Epub ahead of print, - . doi:10.1111/eci.12055
    • Donovan J, Abraham D, Norman J (2013). Platelet-derived growth factor signaling in mesenchymal cells.. Front Biosci (Landmark Ed), 18, 106 - 119.

    2012

    • Donovan J, Denton CP, Norman J, Abraham DA (2012). ANALYSIS OF SPECIFIC PDGFR alpha AND PDGFR beta SIGNAL TRANSDUCTION PATHWAYS IN SSc FIBROBLASTS AND EXAMINATION OF CUTANEOUS WOUND HEALING AND FIBROSIS IN A PDGFR alpha KNOCKOUT MOUSE.
    • Wong YF, Wilson PD, Unwin RJ, Norman JT, Arno M, Hendry BM, Xu Q (2012). Retinoic acid receptor-dependent, cell-autonomous, endogenous retinoic acid signaling and its target genes in mouse collecting duct cells.. PLoS One, 7(9), e45725 - . doi:10.1371/journal.pone.0045725
    • Long DA, Norman JT, Fine LG (2012). Restoring the renal microvasculature to treat chronic kidney disease.. Nat Rev Nephrol, 8(4), 244 - 250. doi:10.1038/nrneph.2011.219
    • Tam A, Sonnylal S, Leask A, Denton CP, de Crombrugghe B, Norman J, Abraham DJ (2012). EPITHELIAL-TO-MESENCHYMAL TRANSITION AND LUNG FIBROSIS.

    2011

    • Norman J (2011). Fibrosis and progression of autosomal dominant polycystic kidney disease (ADPKD).. Biochim Biophys Acta, 1812(10), 1327 - 1336. doi:10.1016/j.bbadis.2011.06.012

    2010

    • Donovan J, Shi-wen X, Rajkumar V, Denton C, Norman J, Abraham D (2010). Selective targeting the platelet-derived growth factor ligand-receptor pathway: relevance to the pathogenesis of systemic sclerosis. CLINICAL AND EXPERIMENTAL RHEUMATOLOGY, 28(5), S63 - S63.
    • Xu SW, Tam A, Sonnylal S, Stratton R, Leask A, Denton CP, Norman J, de Crombrugghe B, Abraham DJ (2010). Epithelial to mesenchymal switching in the pathogenesis of systemic sclerosis. CLIN EXP RHEUMATOL, 28(5), S82 - S82.
    • Lindahl GE, Shi-Wen X, Aggrey-Fynn G, Norman JT, Denton CP, Abraham DJ, Wells AU, Renzoni EA (2010). Global gene expression profiling of scleroderma lung fibroblasts identifies a heterogeneous expression pattern of activated genes and consistent repression of interferon related pathways. CLIN EXP RHEUMATOL, 28(5), S69 - S69.
    • Caplin B, Nitsch D, Gill H, Hoefield R, Blackwell S, MacKenzie D, Cooper JA, Middleton RJ, Talmud PJ, Veitch P, Norman J, Wheeler DC, Leiper JM (2010). Circulating methylarginine levels and the decline in renal function in patients with chronic kidney disease are modulated by DDAH1 polymorphisms.. Kidney Int, 77(5), 459 - 467. doi:10.1038/ki.2009.463

    2008

    • Fine LG, Norman JT (2008). Chronic hypoxia as a mechanism of progression of chronic kidney diseases: from hypothesis to novel therapeutics. KIDNEY INT, 74(7), 867 - 872. doi:10.1038/ki.2008.350

    2007

    • Xu Q, Norman JT, Shrivastav S, Lucio-Canzana J, Kopp JB (2007). In vitro models of TGF-β-induced fibrosis suitable for high-throughput screening of antifibrotic agents. American Journal of Physiology - Renal Physiology, 62(2), F631 - F640.
    • Ruan X, Hunt J, Norman J, Powis S, Varghese Z, Moorhead J, Wheeler D (2007). Inflammation both exacerbates arterial injury and lowers blood lipid levels in an animal model of atherosclerosis.

    2006

    • Norman J (2006). Protecting the microvasculature: a Tie-ght connection to ameliorating chronic kidney disease. Journal of the American Society of Nephrology, 17, 2353 - 2355.

    2005

    • Kumar A, Kingdon E, Norman JT (2005). The isoprostane 8-iso-PGF2alpha inhibits monocyte adhesion to human microvascular endothelial cells via two independent mechanisms.. The FASEB Journal, 19(3), 443 - 445. doi:10.1096/fj.03-1364fje
    • Shakib K, Norman JT, Fine LG, Brown LR, Godovac-Zimmermann J (2005). Proteomics profiling of nuclear proteins for kidney fibroblasts suggests hypoxia, meiosis, and cancer may meet in the nucleus.. Proteomics, 5(11), 2819 - 2838. doi:10.1002/pmic.200401108
    • Kumar A, Kingdon E, Norman J (2005). The isoprostane 8-iso-PGF(2 alpha) suppresses monocyte adhesion to human microvascular endothelial cells via two independent mechanisms. FASEB J, 19(1), 443 - +. doi:10.1096/fj.04-1364fje

    2004

    • Lygoe KA, Norman JT, Marshall JF, Lewis MP (2004). AlphaV integrins play an important role in myofibroblast differentiation.. Wound Repair and Regeneration, 12(4), 461 - 470.
    • Xu Q, Lucio-Cazana J, Kitamura M, Ruan X, Fine LG, Norman JT (2004). Retinoids in nephrology: promises and pitfalls.. Kidney International, 66(6), 2119 - 2131.

    2003

    • Kumar A, Kingdon E, Norman J (2003). The isoprostane 8-iso-PGF2 alpha suppresses monocyte adhesion to microvascular endothelial cells: A role in limiting inflammation?.
    • Xu QH, Lucio-Cazana J, Kitamura M, Fine LG, Norman JT (2003). Retinoic acid induces low-density lipoprotein accumulation in smooth muscle cells and enhances expression of proInflammatory molecules in mesangial cells..
    • Norman JT, Stidwill R, Singer M, Fine LG (2003). Angiotensin II blockade augments renal cortical microvascular pO2 indicating a novel, potentially renoprotective action. Nephron Physiology, 94(2), 39 - 46.

    2002

    • Fine LG, Norman JT (2002). The breathing kidney. Journal of the American Society of Nephrology, 13(7), 1974 - 1976.

    2001

    • Chen J, Brodsky S, Li H, Hampel DJ, Miyata T, Weinstein T, Gafter U, Norman JT, Fine LG, Goligorsky MS (2001). Delayed branching of endothelial capillary-like cords in glycated collagen I is mediated by early induction of PAI-1. American Journal of Physiology - Renal Physiology, 281(1), F71 - F80.
    • Norman JT, Lindahl GE, Shakib K, En-Nia A, Yilmaz E, Mertens PR (2001). The Y-box binding protein YB-1 suppresses collagen alpha 1(I) gene transcription via an evolutionarily conserved regulatory element in the proximal promoter. Journal of Biological Chemistry, 276(32), 29880 - 29890. doi:10.1074/jbc.M103145200
    • Brodsky S, Chen J, Lee A, Akassoglou K, Norman J, Goligorsky MS (2001). Plasmin-dependent and -independent effects of plasminogen activators and inhibitor-1 on ex vivo angiogenesis. American Journal of Physiology - Heart and Circulatory Physiology, 281(4), 1784 - 1792.

    2000

    • Norman JT, Clark IM, Garcia PL (2000). Hypoxia promotes fibrogenesis in human renal fibroblasts. Kidney International, 58(6), 2351 - 2366.
    • Fine LG, Bandyopadhay D, Norman JT (2000). Is there a common mechanism for the progression of different types of renal diseases other than proteinuria? Towards the unifying theme of chronic hypoxia. Kidney International, 57 Sup, S22 - S26.

    1999

    • Norman J, Marshall J, Lewis M (1999). Co-ordination of renal fibrogenesis by collagen-binding integrins.
    • Norman JT, Fine LG (1999). Progressive renal disease: fibroblasts, extracellular matrix, and integrins. Experimental Nephrology, 7(2), 167 - 177.
    • Norman JT, Orphanides C, Garcia P, Fine LG (1999). Hypoxia-induced changes in extracellular matrix metabolism in renal cells. Experimental Nephrology, 7(5-6), 463 - 469.
    • Norman JT, Clark IM, Garcia PL (1999). Regulation of TIMP-1 expression by hypoxia in kidney fibroblasts. Annals of the New York Academy of Sciences, 878, 503 - 505.

    1998

    • Fine LG, Orphanides C, Norman JT (1998). Progressive renal disease: the chronic hypoxia hypothesis. KIDNEY INT SUPPL, 65, S74 - S78.
    • Lewis MP, Norman JT (1998). Differential response of activated versus non-activated renal fibroblasts to tubular epithelial cells: a model of initiation and progression of fibrosis?. Experimental Nephrology, 6(2), 132 - 143.

    1997

    • Orphanides C, Fine LG, Norman JT (1997). Hypoxia stimulates proximal tubular cell matrix production via a TGF-beta1-independent mechanism. KIDNEY INT, 52(3), 637 - 647.
    • Norman J (1997). Mechanisms of hypoxia-induced changes in collagen-I (COLL-I) and tissue inhibitor of metalloproteinase-1 (TIMP-1) gene expression in human renal fibroblasts (HRF).. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 8, A2430 - A2430.
    • Orphanides C, Norman JT (1997). Hypoxia alters integrin expression in human proximal tubular epithelial cells (PTE) and cortical interstitial fibroblasts (CF).. J AM SOC NEPHROL, 8, A2434 - A2434.
    • Norman JT, Goligorsky MS (1997). Ligation of integrin (I) receptors dictates the phenotype of rat kidney fibroblasts (NRK-49F).. J AM SOC NEPHROL, 8, A2431 - A2431.
    • Kuo NT, Norman JT, Wilson PD (1997). Acidic FGF regulation of hyperproliferation of fibroblasts in human autosomal dominant polycystic kidney disease. BIOCHEM MOL MED, 61(2), 178 - 191.

    1996

    • Norman J, Orphanides C (1996). Hypoxia alters extracellular matrix (ECM) synthesis and turnover in renal fibroblasts.. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 7(9), A2577 - A2577.
    • Orphanides C, Fine L, Norman J (1996). Hypoxic modulation of extracellular matrix (ECM) production and turnover by human proximal tubular cells (PTE) is independent of TGF-beta. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 7(9), A2580 - A2580.
    • Lewis MP, Fine LG, Norman JT (1996). Pexicrine effects of basement membrane components on paracrine signalling by renal tubular cells. Kidney International, 49(1), 48 - 58.
    • Norman JT, Lewis MP (1996). Matrix metalloproteinases (MMPs) in renal fibrosis. Kidney International, 49(Suppl. 54), S61 - S63.
    • Norman JT, Wheeler S (1996). High glucose alters renal fibroblast extracellular matrix (ECM) metabolism, growth and activation.. J AM SOC NEPHROL, 7(9), A3149 - A3149.

    1995

    • COHEN EP, NORMAN JT, FINE LG, FISH BL, MOULDER JE (1995). PREVENTION OF INTERSTITIAL FIBROBLAST ACTIVATION IN RADIATION NEPHRITIS. J AM SOC NEPHROL, 6(3), 1011 - 1011.
    • LEWIS MP, FINE LG, NORMAN JT (1995). RAT RENAL FIBROBLASTS AND TUBULAR EPITHELIAL-CELLS BOTH PRODUCE ENZYMES THAT REGULATE MATRIX TURNOVER. KIDNEY INT, 47(2), 673 - 673.
    • LEWIS MP, NORMAN JT (1995). PRO-FIBROGENIC RELEVANCE OF EXPRESSION OF SMOOTH-MUSCLE ACTIN (SMA) BY RENAL FIBROBLASTS - CORRELATION WITH TISSUE INBIBITOR OF METALLOPROTEINASE-1 (TIMP-1) EXPRESSION. J AM SOC NEPHROL, 6(3), 899 - 899.
    • Fine LG, Norman JT, Ong A (1995). Cell-cell cross-talk in the pathogenesis of renal interstitial fibrosis.. Kidney Int Suppl, 49, S48 - S50.
    • NORMAN JT, LEWIS MP, FINE LG, ORPHANIDES C (1995). THE ROLE OF EXTRACELLULAR-MATRIX (ECM) AND GROWTH-FACTORS IN THE ACTIVATION OF RENAL FIBROBLASTS. J AM SOC NEPHROL, 6(3), 905 - 905.
    • NORMAN JT, GATTI L, WILSON PD (1995). EXPRESSION OF MATRIX METALLOPROTEINASES AND TIMP IN NORMAL HUMAN RENAL DEVELOPMENT AND IN AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY-DISEASE (ARPKD). KIDNEY INT, 47(2), 659 - 659.
    • NORMAN J, KUO NT, GATTI L, ORPHANIDES C, WILSON PD (1995). CHANGES IN FIBROBLAST GROWTH AND EXTRACELLULAR-MATRIX METABOLISM IN ADPKD.
    • ORPHANIDES C, NORMAN J (1995). HYPOXIA MODULATES EXPRESSION OF MATRIX METALLOPROTEINASES (MMPS) AND TISSUE INHIBITORS OF METALLO-PROTEINASES (TIMP-1) - A ROLE IN FIBROSIS. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 6(3), 906 - 906.

    1994

    • NORMAN JT, AVNER E, ORPHANIDES C, WILSON PD (1994). CHANGES IN THE EXPRESSION OF MATRIX METALLOPROTEINASES (MMPS) IN A MOUSE MODEL OF POLYCYSTIC KIDNEY-DISEASE (PKD). J AM SOC NEPHROL, 5(3), 817 - 817.
    • FALKENSTEIN D, BURROW CR, NORMAN JT, HARTZ P, WILSON PD (1994). ABNORMALITIES IN MEMBRANE-PROTEIN POLARITY, ENZYME AND ION SECRETION IN HUMAN AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY-DISEASE (ARPKD) EPITHELIA IN-VIVO AND IN-VITRO. J AM SOC NEPHROL, 5(3), 621 - 621.
    • NORMAN JT, HARDY D (1994). POSTTRANSCRIPTIONAL REGULATION OF GENE-EXPRESSION IN COMPENSATORY RENAL HYPERTROPHY. EXP NEPHROL, 2(1), 30 - 39.

    1993

    • Fine LG, Ong AC, Norman JT (1993). Mechanisms of tubulo-interstitial injury in progressive renal diseases.. Eur J Clin Invest, 23(5), 259 - 265.

    • Norman JT, Fine LG (). Intrarenal oxygenation in chronic renal failure. Clin Exp Pharmacol Physiol, , - .
    • Norman JT, Fine LG (). Chronic hypoxia as a mechanism for progressive renal fibrosis. Drug Discovery Today: Disease Mechanisms, 4(1), 29 - 36. doi:10.1016/j.ddmec.2007.06.004