Contact

• workRoom D209 Biodiscovery Institute
  University Park
  Nottingham
  NG7 2RD
  UK
• work0115 823 1063
• fax0115 823 1059
• simon.johnson@nottingham.ac.uk

Biography

• Respiratory Theme Lead Nottingham NIHR Biomedical Research Centre
• Director National Centre for Lymphangioleiomyomatosis
• Co-director Rare Cystic Lung Disease Collaborative Network
• Member of the LAM Foundation scientific board
• Member of the Tuberous Sclerosis Association specialist advisory panel

Expertise Summary

Clinical Interests

Respiratory medicine; Interstitial lung disease; Lymphangioleiomyomatosis; Rare lung disease.

Airway remodelling in asthma is categorised by airway smooth muscle hypertrophy and hyperplasia, change in the type and amount of the extra cellular matrix and epithelial shedding and mucous gland hyperplasia. Our interest is how airway proteases and myofibroblast / extra cellular matrix interactions effect myofibroblast growth and behaviour. These studies employ primary airway cell culture, co-cultures, protein expression, functional activity assay real time PCR and proteomics.

Lymphangioleiomyomatosis (LAM) is a rare lung and lymphatic disease categorised by infiltration of smooth muscle type cells in the lungs and lymphatics leading to progressive respiratory impairment. The disease only effects women and is caused by a defect in one of the two proteins associated with tuberous sclerosis, tuberin and hamartin. Our group has a clinical interest in LAM, runs the UK LAM database and is involved in a number of clinical studies and trials.

Laboratory research projects on LAM include the mechanisms of lung destruction in LAM, prognostic biomarkers and the generation of model systems to study LAM.

Matrix metalloproteinases are proteolytic enzymes secreted by a range of cells and regulated by pro-inflammatory cytokines, growth factors, and extra cellular matrix. We have been studying these in airway myofibroblasts and also specific diseases including chronic obstructive pulmonary disease and LAM.

Research Summary

Metalloproteinases in lung remodelling, Molecular pathology and translational studies in lymphangioleiomyomatosis, COPD, asthma and interstitial lung disease.

Research Group

Dr Debbie Clements Research Fellow: Pathogenesis of LAM

Dr Suzanne Miller Senior Research Fellow: Biomarkers in LAM

Dr Roya Babaei-Jadidi Research Fellow: Pathogenesis of LAM

Andrew Kirkman-Thomas Research Officer NIHR BRC

Selected Publications

• NAVEED SU, CLEMENTS D, JACKSON DJ, PHILP C, BILLINGTON CK, SOOMRO I, REYNOLDS C, HARRISON TW, JOHNSTON SL, SHAW DE and JOHNSON SR, 2016. Matrix Metalloproteinase-1 Activation Contributes to Airway Smooth Muscle Growth and Asthma Severity. American journal of respiratory and critical care medicine. 195(8), 1000-1009
• A DONGRE, D CLEMENTS, A FISHER and SR JOHNSON, 2017. Cathepsin K in Lymphangioleiomyomatosis: LAM Cell-Fibroblast Interactions Enhance Protease Activity by Extracellular Acidification American Journal of Pathology. 30371-1, S0002-9440
• PHILP, CJ, SIEBEKE, I, CLEMENTS, D, HABGOOD, A, JOHN, A, NAVARATNAM, V, HUBBARD, RB, JENKINS, G and JOHNSON, SR, 2017. Extra-cellular matrix cross-linking enhances fibroblast growth and protects against matrix proteolysis in lung fibrosis. American Journal of Respiratory Cell and Molecular Biology.
• DAVIES DM, JOHNSON SR, TATTERSFIELD A, KINGSWOOD JC, COX JA, MCCARTNEY DL, DOYLE T, ELMSLIE F, SAGGAR A, DE VRIES P, SAMPSON JR., 2008. Sirolimus therapy for renal angiomyolipoma in patients with tuberous sclerosis or sporadic lymphangioleiomyomatosis. New England Journal of Medicine. 358, 200-3

• View all publications

• A DONGRE, D CLEMENTS, A FISHER and SR JOHNSON, 2017. Cathepsin K in Lymphangioleiomyomatosis: LAM Cell-Fibroblast Interactions Enhance Protease Activity by Extracellular Acidification American Journal of Pathology. 30371-1, S0002-9440
• PHILP, CJ, SIEBEKE, I, CLEMENTS, D, HABGOOD, A, JOHN, A, NAVARATNAM, V, HUBBARD, RB, JENKINS, G and JOHNSON, SR, 2017. Extra-cellular matrix cross-linking enhances fibroblast growth and protects against matrix proteolysis in lung fibrosis. American Journal of Respiratory Cell and Molecular Biology.
• BEE, J, FULLER, S, MILLER, S and JOHNSON, SR, 2017. Lung function response and side effects to rapamycin for lymphangioleiomyomatosis: a prospective national cohort study Thorax.
• GUPTA, N, FINLAY, GR, KOTLOFF, RM, STRANGE, C, WILSON, KC, YOUNG, LR, TAVEIRA-DASILVA, AM, JOHNSON, SR, SAHN, SA, RYU, JH, SEYAMA, K, DOWNEY, GP, HAN, MK, INOUE, Y, COLBY, TV, WIKENHEISER-BROKAMP, KA, MEYER, C, COTTIN, V, SMITH, K, MOSS, J and MCCORMACK, FX, 2017. Lymphangioleiomyomatosis Diagnosis and Management: An Official American Thoracic Society and Japanese Respiratory Society Clinical Practice Guidelines (2) High-resolution chest CT, Transbronchial Biopsy, and Pleural Disease Management
• HABGOOD AN, TATLER AL, WAHL S, LAURENT GJ, JOHN AE and JOHNSON SR, 2016. Loss of secretory leukocyte protease inhibitor exacerbates the development of pulmonary fibrosis through effects on MMP-9. Lab Invest.
• MCCORMACK FX, GUPTA N, FINLAY GR, YOUNG LR, TAVEIRA-DASILVA AM, GLASGOW CG, STEAGALL WK, JOHNSON SR, SAHN SA, RYU JH, STRANGE C, SEYAMA K, SULLIVAN EJ, KOTLOFF RM, DOWNEY GP, CHAPMAN JT, HAN MK, D'ARMIENTO JM, INOUE Y, HENSKE EP, BISSLER JJ, COLBY TV, KINDER BW, WIKENHEISER-BROKAMP KA, BROWN KK, CORDIER JF, MEYER C, COTTIN V, BROZEK JL, SMITH K, WILSON KC, MOSS J and , 2016. Official American Thoracic Society/Japanese Respiratory Society Clinical Practice Guidelines: Lymphangioleiomyomatosis Diagnosis and Management. American journal of respiratory and critical care medicine. 194(6), 748-61
• KINGSWOOD JC, CRAWFORD P, JOHNSON SR, SAMPSON JR, SHEPHERD C, DEMUTH D, ERHARD C, NASUTI P, PATEL K, MYLAND M, PINNEGAR A, MAGESTRO M and GRAY E, 2016. The economic burden of tuberous sclerosis complex in the UK: A retrospective cohort study in the Clinical Practice Research Datalink. Journal of medical economics. 19(11), 1087-1098
• JOHNSON SR, TAVEIRA-DASILVA AM and MOSS J, 2016. Lymphangioleiomyomatosis. Clinics in chest medicine. 37(3), 389-403
• NUÑEZ O, ROMÁN A, JOHNSON SR, INOUE Y, HIROSE M, CASANOVA Á, DE GARIBAY GR, HERRANZ C, BUENO-MORENO G, BONI J, MATEO F, PETIT A, CLIMENT F, SOLER T, VIDAL A, SÁNCHEZ-MUT JV, ESTELLER M, LÓPEZ JI, GARCÍA N, GUMÀ A, ORTEGA R, PLÀ MJ, CAMPOS M, ANSÓTEGUI E, MOLINA-MOLINA M, VALENZUELA C, USSETTI P, LAPORTA R, ANCOCHEA J, XAUBET A, POLLÁN M and PUJANA MA, 2016. Study of breast cancer incidence in patients of lymphangioleiomyomatosis. Breast cancer research and treatment. 156(1), 195-201
• JOHNSON SR, 2016. Untangling the protease web in COPD: metalloproteinases in the silent zone. Thorax. 71(2), 105-6
• NAVEED SU, CLEMENTS D, JACKSON DJ, PHILP C, BILLINGTON CK, SOOMRO I, REYNOLDS C, HARRISON TW, JOHNSTON SL, SHAW DE and JOHNSON SR, 2016. Matrix Metalloproteinase-1 Activation Contributes to Airway Smooth Muscle Growth and Asthma Severity. American journal of respiratory and critical care medicine. 195(8), 1000-1009
• KRISTENSEN JH, LARSEN L, DASGUPTA B, BRODMERKEL C, CURRAN M, KARSDAL MA, SAND JMB, WILLUMSEN N, KNOX AJ, BOLTON CE, JOHNSON SR, HÄGGLUND P, SVENSSON B and LEEMING DJ, 2015. Levels of circulating MMP-7 degraded elastin are elevated in pulmonary disorders. Clinical biochemistry.
• BEE J, BHATT R, MCCAFFERTY I and JOHNSON SR, 2015. A 4-year prospective evaluation of protocols to improve clinical outcomes for patients with lymphangioleiomyomatosis in a national clinical centre. Thorax.
• SAND JMB, KNOX AJ, LANGE P, SUN S, KRISTENSEN JH, LEEMING DJ, KARSDAL MA, BOLTON CE and JOHNSON SR, 2015. Accelerated extracellular matrix turnover during exacerbations of COPD. Respiratory research. 16(1), 69
• CLEMENTS D, DONGRE A, KRYMSKAYA VP and JOHNSON SR, 2015. Wild type mesenchymal cells contribute to the lung pathology of lymphangioleiomyomatosis. PloS one. 10(5), e0126025
• CANE JL, MALLIA-MILLANES B, FORRESTER DL, KNOX AJ, BOLTON CE and JOHNSON SR, 2015. Matrix metalloproteinases -8 and -9 in the Airways, Blood and Urine During Exacerbations of COPD. Copd. 13(1), 26-34
• KINGSWOOD C, BOLTON P, CRAWFORD P, HARLAND C, JOHNSON SR, SAMPSON JR, SHEPHERD C, SPINK J, DEMUTH D, LUCCHESE L, NASUTI P, GRAY E, PINNEGAR A and MAGESTRO M, 2015. The clinical profile of tuberous sclerosis complex (TSC) in the United Kingdom: A retrospective cohort study in the Clinical Practice Research Datalink (CPRD). European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society. 20(2), 296-308
• CHANG WYC, CANE JL, KUMARAN M, LEWIS S, TATTERSFIELD AE, JOHNSON SR., 2014. A two year randomised placebo controlled trial of doxycycline for lymphangioleiomyomatosis. European Respiratory Journal.
• ROGERS NK, CLEMENTS D, DONGRE A, HARRISON TW, SHAW D and JOHNSON SR, 2014. Expression of Tenascin-C in Airway Remodelling in Asthma induces Metalloproteinase-1 activity and increases Airway Smooth Muscle Contraction. Plos One. 9(2), e90565
• CHERNYAVSKY IL, CROISIER H, CHAPMAN LAC, KIMPTON LS, HIORNS JE, PHILLIPS J, BROOK BS, JENSEN OE, BILLINGTON CK, HALL IP and JOHNSON SR, 2014. New strategies to control inflammation-driven airway smooth muscle remodeling in asthma: insight from a theoretical model. Plos One. 10,
• YEOH ZW, NAVARATNAM V, NAVARATNAM V, BHATT R, HUBBARD RB and JOHNSON SR, 2014. Natural history of angiomyolipoma in lymphangioleiomyomatosis: implications for screening and surveillance. Orphanet Journal of Rare Diseases. 9,
• NAVARATNAM, V., FOGARTY, A.W., MCKEEVER, T., THOMPSON, N., JENKINS, G., JOHNSON, S.R., DOLAN, G., KUMARAN, M., POINTON, K. and HUBBARD, R.B., 2013. Presence of a prothrombotic state in people with idiopathic pulmonary fibrosis: a population-based case-control study Thorax. 69(3), 207-15
• LUISETTI M, BALFOUR-LYNN I, JOHNSON S, MIRAVITLLES M, STRANGE C, TRAPNELL B, VOGELMEIER C and BRONSWIJK H., 2012. Perspectives for improving the evaluation and access of therapies for rare lung diseases in Europe. Respiratory Medicine.
• CHANG WYC, CANE J, KUMARAN M, POINTON KS, BLAKEY J and JOHNSON SR., 2012. Application of diagnostic guidelines and putative biomarkers in lymphangioleiomyomatosis. Respiratory Research.
• MARKWICK LJ, CLEMENTS D, ROBERTS ME, CERESA CC, KNOX AJ and JOHNSON SR, 2012. CCR3 induced-p42/44 MAPK activation protects against staurosporine induced-DNA fragmentation but not apoptosis in airway smooth muscle cells. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 42(7), 1040-50
• GAZI, U., ROSAS, M., SINGH, SONALI, HEINSBROEK, S., HAQ, I., JOHNSON, S., BROWN, G.D., WILLIAMS, D.L., TAYLOR, P.R. and MARTINEZ-POMARES, L., 2011. Fungal recognition enhances mannose receptor shedding through dectin-1 engagement Journal of Biological Chemistry. 286(10), 7822-7829
• HARKNETT EC, CHANG WYC, BYRNES S, JOHNSON J, LAZOR R, COHEN MM, GRAY B, GEILING S, TELFORD H, TATTERSFIELD AE, HUBBARD RB, JOHNSON SR., 2011. Regional and National Variability Suggests Underestimation of Prevalence of Lymphangioleiomyomatosis Quarterly Journal of Medicine. (In Press.)
• ROBERTS, M.E., MAGOWAN, L., HALL, I.P. and JOHNSON, S.R., 2011. Discoidin domain receptor 1 regulates bronchial epithelial repair and matrix metalloproteinase production European Respiratory Journal. 37(6), 1482-1493
• DAVIES, D.M., DE VRIES, P.J., JOHNSON, S.R., MCCARTNEY, D.L., COX, J.A., SERRA, A.L., WATSON, P.C., HOWE, C.J., DOYLE, T., POINTON, K., CROSS, J.J., TATTERSFIELD, A.E., KINGSWOOD, J.C. and SAMPSON, J.R., 2011. Sirolimus therapy for angiomyolipoma in tuberous sclerosis and sporadic lymphangioleiomyomatosis: a phase 2 trial Clinical Cancer Research: an official journal of the American Association for Cancer Research. 17(June), 4071-4081
• HAQ, I., LOWREY, G.E., KALSHEKER, N. and JOHNSON, S.R., 2011. Matrix metalloproteinase-12 (MMP-12) SNP affects MMP activity, lung macrophage infiltration and protects against emphysema in COPD Thorax. 66(11), 970-976
• HAQ, IMRAN, CHAPPELL, SALLY, JOHNSON, SIMON R, LOTYA, JUZER, DALY, LESLIE, MORGAN, KEVIN, GUETTA-BARANES, TAMAR, ROCA, JOSEP, RABINOVICH, ROBERTO, MILLAR, ANN, DONNELLY, SEAMAS C, KEATINGS, VERA, MACNEE, WILLIAM, STOLK, JAN, HIEMSTRA, PIETER, MINIATI, MASSIMO, MONTI, SIMONETTA, O'CONNOR, CLARE and KALSHEKER, NOOR, 2010. Association of MMP - 12 polymorphisms with severe and very severe COPD: A case control study of MMPs - 1, 9 and 12 in a European population. BMC Medical Genetics. 11(1), 7
• CHANG WYC, CLEMENTS D and JOHNSON SR, 2010. Effect of doxycycline on proliferation, MMP production, and adhesion in LAM-related cells. American journal of physiology. Lung cellular and molecular physiology. 299(3), L393-400
• JOHNSON, S R, CORDIER, J F, LAZOR, R, COTTIN, V, COSTABEL, U, HARARI, S, REYNAUD-GAUBERT, M, BOEHLER, A, BRAUNER, M, POPPER, H, BONETTI, F, KINGSWOOD, C and ,, 2010. European Respiratory Society guidelines for the diagnosis and management of lymphangioleiomyomatosis. The European respiratory journal. 35(1), 14-26
• JOHNSON, SIMON R, 2010. The ERS guidelines for LAM: Trying a rationale approach to a rare disease. Respiratory medicine.
• CLEMENTS, D., MARKWICK, L.J., PURI, N. and JOHNSON, S.R., 2010. Role of the CXCR4/CXCL12 axis in lymphangioleiomyomatosis and angiomyolipoma Journal of Immunology. 185(3), 1812–1821
• NUROK, MICHAEL, ESLICK, IAN, CARVALHO, CARLOS R R, COSTABEL, ULRICH, D'ARMIENTO, JEANINE, GLANVILLE, ALLAN R, HARARI, SERGIO, HENSKE, ELIZABETH P, INOUE, YOSHIKAZU, JOHNSON, SIMON R and LACRONIQUE, JACQU, 2010. The International LAM Registry: a component of an innovative web-based clinician, researcher, and patient-driven rare disease research platform. Lymphatic research and biology. 8(1), 81-7
• CLEMENTS, D., ASPREY, S.L., MCCULLOCH, T.A., MORRIS, T.A., WATSON, S.A. and JOHNSON, S.R., 2009. Analysis of the oestrogen response in an angiomyolipoma derived xenograft model Endocrine-Related Cancer. 16(1), 59-72
• BURGESS JK, CERESA C, JOHNSON S, KANABAR V, MOIR LM, NGUYEN TTB, OLIVER BGG, SCHULIGA M, STEWART A, WARD J., 2009. Tissue and matrix influences on airway smooth muscle function. Pulmonary Pharmacology and Therapeutics.. 22, 379-387
• LOWREY GE, HENDERSON N, BLAKEY JD, CORNE JM AND JOHNSON SR., 2008. MMP-9 protein level does not reflect overall MMP activity in the airways of patients with COPD. Respiratory Medicine. 102, 845-51
• DAVIES DM, JOHNSON SR, TATTERSFIELD A, KINGSWOOD JC, COX JA, MCCARTNEY DL, DOYLE T, ELMSLIE F, SAGGAR A, DE VRIES P, SAMPSON JR., 2008. Sirolimus therapy for renal angiomyolipoma in patients with tuberous sclerosis or sporadic lymphangioleiomyomatosis. New England Journal of Medicine. 358, 200-3
• HENDERSON, N., MARKWICK, L.J., ELSHAW, S.R., FREYER, A.M., KNOX, A.J. and JOHNSON, S.R., 2007. Collagen I and thrombin activate MMP-2 by MMP-14 dependent and -independent pathways: implications for airway smooth muscle migration. American Journal of Physiology: Lung Cellular and Molecular Physiology. 292(4), L1030-L1038
• CLEMENTS, D., MAYER, R.J. and JOHNSON, S.R., 2007. Sub-cellular distribution of the TSC2 gene product tuberin in human airway smooth muscle cells is driven by multiple localisation sequences and is cell cycle dependent. American Journal of Physiology - Lung Cellular and Molecular Physiology. 292, L258-L266
• POLLOCK-BARZIV,S.M., COHEN,M.M., DOWNEY,G.P., JOHNSON,S.R., SULLIVAN,E. and MCCORMACK,F.X., 2007. Air travel in women with lymphangioleiomyomatosis Thorax. 62, 176-180
• JOHNSON, S R, 2006. Lymphangioleiomyomatosis. European Respiratory Journal. 27(5), 1056-65
• COHEN, M.M., POLLOCK-BARZIV, S. and JOHNSON, S.R., 2005. Emerging clinical picture of lymphangioleiomyomatosis Thorax. 60(10), 875-879
• ELSHAW, SHONA R, HENDERSON, NEIL, KNOX, ALAN J, WATSON, SUSAN A, BUTTLE, DAVID J and JOHNSON, SIMON R, 2004. Matrix metalloproteinase expression and activity in human airway smooth muscle cells. British Journal of Pharmacology. 142(8), 1318-24
• JOHNSON, S.R., WHALE, C.I., HUBBARD, R.B., LEWIS, S.A. and TATTERSFIELD, A.E., 2004. Survival and disease progression in UK patients with lymphangioleiomyomatosis Thorax. 59(9), 800-803
• BURROWS, N J and JOHNSON, S R, 2004. Pulmonary artery aneurysm and tuberous sclerosis. Thorax. 59(1), 86
• WHALE, C I, JOHNSON, S R, PHILLIPS, K G, NEWTON, S A, LEWIS, S A and TATTERSFIELD, A E, 2003. Lymphangioleiomyomatosis: a case-control study of perinatal and early life events. Thorax. 58(11), 979-82
• JOHNSON, S R, CLELLAND, C A, RONAN, J, TATTERSFIELD, A E and KNOX, A J, 2002. The TSC-2 product tuberin is expressed in lymphangioleiomyomatosis and angiomyolipoma. Histopathology. 40(5), 458-63
• JOHNSON, S. R. and TATTERSFIELD, A. E., 2002. Lymphangioleiomyomatosis Seminars in Respiratory and Critical Care Medicine. VOL 23(PART 2), 85-92
• JOHNSON, S. R., 2002. An assay to evaluate the long term effects of inflammatory mediators on airway smooth muscle: evidence that TNF~a~l~p~h~a upregulates 5-HT~2~A mediated contraction British Journal of Pharmacology. VOL 137(PART 7), 943-944
• FREYER, A.M., JOHNSON, S.R. and HALL, I.P., 2001. Effects of growth factors and extracellular matrix on survival of human airway smooth muscle cells. American Journal of Respiratory Cell and Molecular Biology. 25(5), 569-576
• HAMAD, A. M., JOHNSON, S. R. and KNOX, A. J., 1999. Antiproliferative effects of NO and ANP in cultured human airway smooth muscle American Journal of Physiology. VOL 277(ISSUE 5), L910-L918
• JOHNSON, S and KNOX, A, 1999. Autocrine production of matrix metalloproteinase-2 is required for human airway smooth muscle proliferation. American Journal of Physiology. 277(6 Pt 1), L1109-17
• JOHNSON, S. R. and TATTERSFIELD, A. E., 1999. Decline in Lung Function in Lymphangioleiomyomatosis: Relation to Menopause and Progesterone Treatment American Journal of Respiratory and Critical Care Medicine. VOL 160(NUMBER 2), 628-633
• JOHNSON, S R and KNOX, A J, 1997. Synthetic functions of airway smooth muscle in asthma. Trends in Pharmacological Sciences. 18(8), 288-92