Dr. Allan Lawrie BSc PhD

BHF Senior Basic Science Research FellowDr Allan Lawrie

Head of Pulmonary Vascular Research Group

Address
Department of Cardiovascular Science
University of Sheffield
Medical School
Beech Hill Road
Sheffield S10 2RX
Tel: +44 (0)114 271 3176
Fax: +44 (0)114 271 1863
Email: a.lawrie@sheffield.ac.uk
Secretary: Miss Vicky Rowberry
Telephone Number: 0114 271 2052
Secretary Email: v.rowberry@sheffield.ac.uk

Biography:

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.

Research Interests:

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.

Teaching Interests:

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.

Professional Activities:

  • 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 Circulation, Circulations Research, Arteriosclerosis, Thrombosis and Vascular Biology, European Respiratory Journal and Thorax.
  • Pulmonary Vascular Research Institute (PVRI) Task Force on Animal Models and Phenotying.

Current Projects:

  • 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).
  • March 2013 - June 2014 The Medical Research Council Confidence in Concepts. Radiofrequency ablation of pulmonary hypertension. (Co-PI - £48,461).
  • April 2012 - March 2015 (BHF Project grant) Investigation into OPG and related biomarkers in incident cases of pulmonary hypertension. (PI - £278,564).

Key Publications:

  1. Hameed A, Bennett E, Ciani B, Hoebers L, Milner R, Lawrie A, Francis S, Grierson A. No evidence for cardiac dysfunction in Kif6 mutant mice. PLoS One 2013;8(1):e54636.

  2. Rhodes C, Wharton J, Boon R, Roexe T, Tsang H, Wojciak-Stothard B, Chakrabarti A, Howard L, Gibbs J, Lawrie A, Condliffe R, Elliot C, Kiely D, Huson L, Ghofrani H, Tiede H, Schermuly R, Zeiher A, Dimmeler S, Wilkins M. Reduced miR-150 is associated with poor survival in pulmonary arterial hypertension. American Journal of Respiratory and Critical Care Medicine. 2013;187(3):294-302.

  3. 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. Targeting tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) prevents and reverses experimental models of pulmonary arterial hypertension. Journal of Experimental Medicine. 2012; 209:1919–1935. Access the recommendation on F1000 Prime.

  4. Condliffe R, Pickworth JA, Hopkinson K, Walker SJ, Hameed AG, Suntharaligam J, Soon E, Treacy C, Pepke-Zaba J, Francis SE, Crossman DC, Newman CM, Elliot CA, Morton AC, Morrell NW, Kiely DG, Lawrie A. Serum osteoprotegerin is increased and predicts survival in idiopathic pulmonary arterial hypertension. Pulm Circ. 2012; 2:21–27.

  5. Lawrie A, Hameed AG, Chamberlain J, Arnold N, Kennerley A, Hopkinson K, Pickworth J, Kiely DG, Crossman DC, Francis SE. Paigen Diet–Fed Apolipoprotein E Knockout Mice Develop Severe Pulmonary Hypertension in an Interleukin-1–Dependent Manner. Am J Pathol. 2011; 179:1693–1705.

  6. McGrath EE, Lawrie A, Marriott HM, Mercer P, Cross SS, Arnold ND, Singleton V, Thompson AAR, Walmsley SR, Renshaw SA, Sabroe I, Chambers RC, Dockrell DH, Whyte MKB. Deficiency of tumour necrosis factor-related apoptosis-inducing ligand exacerbates lung injury and fibrosis. Thorax. 2012.

  7. McGrath EE, Marriott HM, Lawrie A, Francis SE, Sabroe I, Renshaw SA, Dockrell DH, Whyte MKB. TNF-related apoptosis-inducing ligand (TRAIL) regulates inflammatory neutrophil apoptosis and enhances resolution of inflammation. J Leukoc Biol. 2011; 90:855–865.

  8. Spiekerkoetter E, Guignabert C, de Jesus Perez V, Alastalo T, Powers JM, Wang L, Lawrie A, Ambartsumian N, Schmidt AM, Berryman M, Ashley RH and Rabinovitch M. S100A4 and BMP-2 Co-Dependently Induce Vascular Smooth Muscle Cell Migration via pERK and Chloride Intracellular Channel 4 (CLIC4). Circulation Research 2009 (105):639-647.

  9. Lawrie A, Waterman EA, Evans DJ, Southwood M, Suntharalingam J, Francis SE, Crossman DC, Croucher PI, Morrell NW and Newman CM. Evidence of a role for osteoprotegerin in the pathogenesis of pulmonary arterial hypertension. The American Journal of Pathology 2008 172(1):256-264.

  10. Lawrie A, Spiekerkoetter E, Martinez EC, Ambartsumian N, Sheward WJ, MacLean MR, Harmar AJ, Schmidt AM, Lukanidin E and Rabinovitch M. Interdependent serotonin transporter and receptor pathways regulate S100A4/Mts1, a gene associated with pulmonary vascular disease. Circulation Research 2005. 97(3):227-35.

  11. Akowuah EF, Gray C, Lawrie A, Sheridan PJ, Su CH, Bettinger T, Brisken AF, Gunn J, Crossman DC, Francis SE, Baker AH and Newman CM. Ultrasound-mediated delivery of TIMP-3 plasmid DNA into saphenous vein leads to increased lumen size in a porcine interposition graft model. Gene Therapy 2005. 12(14):1154-7.

  12. Leung WC, Lawrie A, Demaries S, Massaeli H, Burry A, Yablonsky S, Sarjeant JM, Fera E, Rassart E, Pickering JG and Rabinovitch M. Apolipoprotein D and platelet-derived growth factor-BB synergism mediates vascular smooth muscle cell migration. Circulation Research 2004. 95(2):179-86.

  13. Sarjeant JM, Lawrie A, Kinnear C, Yablonsky S, Leung W, Massaeli H, Prichett W, Veinot JP, Rassart E and Rabinovitch M. 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. Arteriosclerosis Thrombosis and Vascular Biology 2003. 23(12):2172-7.

  14. Lawrie A, Brisken AF, Francis SE, Wyllie D, Kiss-Toth E, Qwarnstrom EE, Dower SK, Crossman DC and Newman CM. Ultrasound-enhanced transgene expression in vascular cells is not dependent upon cavitation-induced free radicals. Ultrasound in Medicine and Biology 2003. 29(10):1453-61.

  15. Lawrie A, Brisken AF, Francis SE, Cumberland DC, Crossman DC and Newman CM. Microbubble-enhanced ultrasound for vascular gene delivery. Gene Therapy 2000. 7(23):2023-7.

  16. Lawrie A, Brisken AF, Francis SE, Tayler DI, Chamberlain J, Crossman DC, Cumberland DC and Newman CM. Ultrasound enhances reporter gene expression after transfection of vascular cells in vitro. Circulation 1999. 99(20):2617-20.

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