Dr. Allan Lawrie BSc PhD
BHF Senior Basic Science Research Fellow
Head of Pulmonary Vascular Research Group
Department of Infection, Immunity & Cardiovascular Disease
University of Sheffield
Beech Hill Road
Tel: +44 (0)114 215 9536
Fax: +44 (0)114 271 1863
I completed my PhD “The effects of ultrasound on vascular gene delivery” in the Department of Cardiovascular Science at the University of Sheffield at the end of 2001. I then started my post-doctoral studies under the mentorship of Professor Marlene Rabinovitch at Stanford University, California where I developed my interested in Pulmonary Hypertension. I gained my first independent Fellowship to return to Sheffield at the end of 2004 (Russell Fellowship) and started to build a basic science group focused on pulmonary hypertension research. I obtained a Medical Research Council Career Development Award Fellowship in 2008 to build upon this programme of research and now hold a British Heart Foundation Senior Basic Science Research Fellowship. I lead a talented group of research scientists and students and maintain strong translational links through the Sheffield Pulmonary Vascular Disease Unit at the Royal Hallamshire Hospital.
My main research interest lies in better understanding the molecular mechanism of pulmonary arterial hypertension (PAH). In particular I am currently studying the role of osteoprotegerin (OPG), Tumor necrosis factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) and other related members of the TNF superfamily in the pathogenesis of PAH. I have an additional interest in the role inflammation, particularly IL-1, plays in modulating disease.
I also have a strong interest in biomarkers (proteomic, miRNA and epigenetic) and through collaboration with clinical colleagues in the SPVDU have developed a growing biobank of blood products (DNA/RNA/Plasma/Serum) from patients with pulmonary hypertension, with sample collected at diagnosis and subsequent visits post treatment. I have developed a number of national and international collaborations to maximise the utilisation of this valuable and rare resource.
I currently teach on the MSc in Molecular Medicine course. I cover topics such as RNA interference, micro RNA and gene delivery. On the Cardiovascular Pathway I cover the areas of vascular cell biology and pre-clinical models relating to pulmonary hypertension.
- Member of the American Thoracic Society’s Pulmonary Circulation Program Committee for 2010-present.
- Grant Reviewer for MRC, Wellcome Trust, BHF, BBSRC, Arthritis Research UK, The Scleroderma Society.
- Manuscript Reviewer for the leading journals in the field including Nature, Journal of Clinical Investigation, Circulation, Circulations Research, American Journal of Respiratory and Critical Care Medicine, European Respiratory Journal and Thorax.
- Pulmonary Vascular Research Institute (PVRI) Task Force on Animal Models and Phenotying.
- May 2014 - April 2016 Medical Research Council DPFS MICA. Developing novel human antibodies targeting the OPG/TRAIL axis for the treatment of pulmonary arterial hypertension (PAH). (£516,153).
- December 2013 - November 2018 BHF Senior Basic Science Research Fellowship. Defining cellular and molecular interactions in the OPG pathway in pulmonary arterial hypertension. (£1,010,100).
- May 2013 - April 2018 Medical Research Council/British Heart Foundation (Experimental Medicine Grand Challenge Grant). National cohort study of heritable and idiopathic pulmonary arterial hypertension. (Co-Applicant. PI Prof Nicholas Morrell, Cambridge - £3.4m).
- November 2012 - October 2015 MRC Clinical Research Training Fellowship (Dr Alex Rothman) Investigation into MiR-140-5p in human and experimental models of pulmonary arterial hypertension. (Sponsor/Supervisor - £292,383).
For key publications see below. For a full list of publications click here.
- Gräf S, Haimel M, Bleda M, Hadinnapola C, Southgate L, Li W, Hodgson J, Liu B, Salmon RM, Southwood M, Machado RD, Martin JM, Treacy CM, Yates K, Daugherty LC, Shamardina O, Whitehorn D, Holden S, Aldred M, Bogaard HJ, Church C, Coghlan G, Condliffe R, Corris PA, Danesino C, Eyries M, Gall H, Ghio S, Ghofrani HA, Gibbs JSR, Girerd B, Houweling AC, Howard L, Humbert M, Kiely DG, Kovacs G, MacKenzie Ross RV, Moledina S, Montani D, Newnham M, Olschewski A, Olschewski H, Peacock AJ, Pepke-Zaba J, Prokopenko I, Rhodes CJ, Scelsi L, Seeger W, Soubrier F, Stein DF, Suntharalingam J, Swietlik EM, Toshner MR, Van Heel DA, Vonk Noordegraaf A, Waisfisz Q, Wharton J, Wort SJ, Ouwehand WH, Soranzo N, Lawrie A, Upton PD, Wilkins MR, Trembath RC & Morrell NW (2018) Identification of rare sequence variation underlying heritable pulmonary arterial hypertension. Nature Communications, 9(1). View this article in WRRO
- Chen K-H, Dasgupta A, Lin J, Potus F, Bonnet S, Iremonger J, Fu J, Mewburn J, Wu D, Dunham-Snary K, Theilmann AL, Jing Z-C, Hindmarch C, Ormiston ML, Lawrie A & Archer SL (2018) Epigenetic Dysregulation of the Drp1 Binding Partners MiD49 and MiD51 Increases Mitotic Mitochondrial Fission and Promotes Pulmonary Arterial Hypertension: Mechanistic and Therapeutic Implications.. Circulation. View this article in WRRO
- Hadinnapola C, Bleda M, Haimel M, Screaton N, Swift AJ, Dorfmüller P, Preston SD, Southwood M, Hernandez-Sanchez J, Martin J, Treacy C, Yates K, Bogaard H, Church C, Coghlan G, Condliffe R, Corris PA, Gibbs SR, Girerd B, Holden S, Humbert M, Kiely DG, Lawrie A, Machado RD, MacKenzie Ross R, Moledina S, Montani D, Newnham M, Peacock AJ, Pepke-Zaba J, Rayner-Matthews PJ, Shamardina O, Soubrier F, Southgate L, Suntharalingam J, Toshner MR, Trembath RC, Vonk Noordegraaf A, Wilkins MR, Wort SJ, Wharton J, Gräf S, Morrell NW & NIHR BioResource - Rare Diseases Consortium & UK National Cohort Study of Idiopathic and Heritable PAH (2017) Phenotypic Characterisation of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically with Pulmonary Arterial Hypertension.. Circulation, 136(21), 2022-2033. View this article in WRRO
- Rhodes CJ, Wharton J, Ghataorhe P, Watson G, Girerd B, Howard LS, Gibbs JSR, Condliffe R, Elliot CA, Kiely DG, Simonneau G, Montani D, Sitbon O, Gall H, Schermuly RT, Ghofrani HA, Lawrie A, Humbert M & Wilkins MR (2017) Plasma proteome analysis in patients with pulmonary arterial hypertension: an observational cohort study. The Lancet Respiratory Medicine, 5(9), 717-726. View this article in WRRO
- Rothman AM, Arnold N, Pickworth J, Iremonger J, Ciuclan L, Allan R, Guth-Gundel S, Southwood M, Morrell N, Thomas M, Francis S, Rowlands D & Lawrie A (2016) MicroRNA-140-5p and SMURF1 regulate pulmonary arterial hypertension. Journal of Clinical Investigation, 126(7), 2495-2508. View this article in WRRO
- Rhodes CJ, Wharton J, Boon RA, Roexe T, Tsang H, Wojciak-Stothard B, Chakrabarti A, Howard LS, Gibbs JSR, Lawrie A, Condliffe R, Elliot CA, Kiely DG, Huson L, Ghofrani HA, Tiede H, Schermuly R, Zeiher AM, Dimmeler S & Wilkins MR (2013) Reduced microRNA-150 is associated with poor survival in pulmonary arterial hypertension.. Am J Respir Crit Care Med, 187(3), 294-302.
- Hameed A, Bennett E, Ciani B, Hoebers LPC, Milner R, Lawrie A, Francis SE & Grierson AJ (2013) No evidence for cardiac dysfunction in Kif6 mutant mice.. PLoS One, 8(1), e54636. View this article in WRRO
- Hameed AG, Arnold ND, Chamberlain J, Pickworth JA, Paiva C, Dawson S, Cross S, Long L, Zhao L, Morrell NW, Crossman DC, Newman CMH, Kiely DG, Francis SE & Lawrie A (2012) Inhibition of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) reverses experimental pulmonary hypertension.. J Exp Med, 209(11), 1919-1935. View this article in WRRO
- Condliffe R, Pickworth JA, Hopkinson K, Walker SJ, Hameed AG, Suntharaligam J, Soon E, Treacy C, Pepke-Zaba J, Francis SE, Crossman DC, Newman CMH, Elliot CA, Morton AC, Morrell NW, Kiely DG & Lawrie A (2012) Serum osteoprotegerin is increased and predicts survival in idiopathic pulmonary arterial hypertension.. Pulm Circ, 2(1), 21-27. View this article in WRRO
- McGrath EE, Marriott HM, Lawrie A, Francis SE, Sabroe I, Renshaw SA, Dockrell DH & Whyte MKB (2011) TNF-related apoptosis-inducing ligand (TRAIL) regulates inflammatory neutrophil apoptosis and enhances resolution of inflammation.. J Leukoc Biol, 90(5), 855-865. View this article in WRRO
- Lawrie A, Hameed AG, Chamberlain J, Arnold N, Kennerley A, Hopkinson K, Pickworth J, Kiely DG, Crossman DC & Francis SE (2011) Paigen diet-fed apolipoprotein e knockout mice develop severe pulmonary hypertension in an interleukin-1-Dependent Manner. American Journal of Pathology, 179(4), 1693-1705. View this article in WRRO
- Spiekerkoetter E, Guignabert C, Perez VD, Alastalo TP, Powers JM, Wang LL, Lawrie A, Ambartsumian N, Schmidt AM, Berryman M, Ashley RH & Rabinovitch M (2009) S100A4 and Bone Morphogenetic Protein-2 Codependently Induce Vascular Smooth Muscle Cell Migration via Phospho-Extracellular Signal-Regulated Kinase and Chloride Intracellular Channel 4. CIRC RES, 105(7), 639-U37.
- Lawrie A, Waterman E, Southwood M, Evans D, Suntharalingam J, Francis S, Crossman D, Croucher P, Morrell N & Newman C (2008) Evidence of a role for osteoprotegerin in the pathogenesis of pulmonary arterial hypertension.. Am J Pathol, 172(1), 256-264.
- Akowuah EF, Gray C, Lawrie A, Sheridan PJ, Su C-H, Bettinger T, Brisken AF, Gunn J, Crossman DC, Francis SE, Baker AH & Newman CM (2005) Ultrasound-mediated delivery of TIMP-3 plasmid DNA into saphenous vein leads to increased lumen size in a porcine interposition graft model.. Gene Ther, 12(14), 1154-1157.
- Lawrie A, Spiekerkoetter E, Martinez EC, Ambartsumian N, Sheward WJ, MacLean MR, Harmar AJ, Schmidt AM, Lukanidin E & Rabinovitch M (2005) Interdependent serotonin transporter and receptor pathways regulate S100A4/Mts1, a gene associated with pulmonary vascular disease. Circulation Research, 97(3), 227-235.
- Leung WCY, Lawrie A, Demaries S, Massaeli H, Burry A, Yablonsky S, Sarjeant JM, Fera E, Rassart E, Pickering JG & Rabinovitch M (2004) Apolipoprotein D and platelet-derived growth factor-BB synergism mediates vascular smooth muscle cell migration. CIRC RES, 95(2), 179-186.
- Sarjeant JM, Lawrie A, Kinnear C, Yablonsky S, Leung W, Massaeli H, Prichett W, Veinot JP, Rassart E & Rabinovitch M (2003) Apolipoprotein D inhibits platelet-derived growth factor-BB-induced vascular smooth muscle cell proliferated by preventing translocation of phosphorylated extracellular signal regulated kinase 1/2 to the nucleus. ARTERIOSCL THROM VAS, 23(12), 2172-2177.
- Lawrie A, Brisken AF, Francis SE, Wyllie D, Kiss-Toth E, Qwarnstrom EE, Dower SK, Crossman DC & Newman CM (2003) Ultrasound-enhanced transgene expression in vascular cells is not dependent upon cavitation-induced free radicals.. Ultrasound Med Biol, 29(10), 1453-1461.
- Lawrie A, Brisken AF, Francis SE, Cumberland DC, Crossman DC & Newman CM (2000) Microbubble-enhanced ultrasound for vascular gene delivery.. Gene Ther, 7(23), 2023-2027.
- Lawrie A, Brisken AF, Francis SE, Tayler DI, Chamberlain J, Crossman DC, Cumberland DC & Newman CM (1999) Ultrasound enhances reporter gene expression after transfection of vascular cells in vitro.. Circulation, 99(20), 2617-2620.