Dr. Allan Lawrie BSc PhDAllan Lawrie

BHF Senior Basic Science Research Fellow
Head of Pulmonary Vascular Research Group

Department of Infection, Immunity & Cardiovascular Disease
University of Sheffield
Medical School
Beech Hill Road
Sheffield
S10 2RX
Tel: +44 (0)114 215 9536
Fax: +44 (0)114 271 1863
Email: a.lawrie@sheffield.ac.uk

Biography:

I completed my PhD “The effects of ultrasound on vascular gene delivery” (Supervisor”: Prof Chris Newman) in the Department of Cardiovascular Science at the University of Sheffield at the end of 2001. I followed this with a post-doctoral position with Prof 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 research group focused understanding the molecular mechanisms underlying pulmonary hypertension. I obtained a Medical Research Council Career Development Award in 2008 and now hold a British Heart Foundation Senior Basic Science Research Fellowship (since 2012). Within the newly formed Donald Heath programme I lead a talented group of scientists and maintain strong translational links through the Sheffield Pulmonary Vascular Disease Unit at the Royal Hallamshire Hospital working towards my core research interests of drug target identification, novel therapies and early disease diagnosis.

Research Interests:

My group has a strong interest in understanding the molecular mechanisms underlying pulmonary arterial hypertension (or PAH). We have a strong translational and collaborative focus working with the Sheffield Pulmonary Vascular Disease Unit, nationally with all UK PH Centres through the UK Idiopathic and Heritable Pulmonary Arterial Hypertension Cohort, and multiple international collaborations.

Drug target identification / development: Work in my lab identified the Osteoprotegerin (OPG) / Tumor necrosis factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) axis as both key regulators of disease pathogenesis and therapeutic targets (Lawrie et al Am J Pathol 2008, Hameed et al JEM 2012). Working though MRC:MICA Developmental Pathway Funding Scheme, in partnership with Kymab Ltd we have identified and patented a human therapeutic antibody targeting OPG.

I also have a strong interest in the role of inflammation, specifically IL-1 (Lawrie et al Am J Path 2011) in PAH, and on the regulation of BMPR2 signalling (Pickworth et al Pulm Circ 2017) in the lung and in miRNA and non-coding RNA biology. We have identified a number of key miRNA that offer diagnostic, prognostic and therapeutic potential. Once such example under further study is miR-140-5p which we have recently shown to be a regulator of BMP signalling, a potential explanation for reduced BMPR2 expression independent of mutation, and identified SMURF1 as a potential drug target (Rothman et al JCI 2016). Several other individual miRNA are currently under investigation including miR-34a.

Biomarkers and Precision Medicine for Pulmonary Arterial Hypertension: Through developing the Sheffield Pulmonary Hypertension Biobank (blood derived DNA/RNA/Plasma/Serum from patients with all major forms of PH) I have a strong interest in biomarkers (proteomic, miRNA and epigenetic). I have developed a number of national and international collaborations to maximise the utilisation of this valuable and rare resource (e.g. Nick Morrell (Cambridge) / Martin Wilkins (Imperial) / Roham Zamanian (Stanford)). The combination of clinical phenotype with biological data from multi-omic studies including whole genome sequencing (Gräf et al Nat. Comms 2018), RNA expression, miRNA (Rhodes et al AMRCCM 2013, Rothman et al JCI 2016), proteomics (Rhodes et al Lancet Resp Med 2017) and metabolomics (Rhodes et al Circulation 2017) offers great potential to identify novel drug targets, and develop tools for Precision Medicine.

Early detection: Working with our partner IQVIA and GSK we are currently exploring the potential for harnessing real-world healthcare resource utilisation data in the form of NHS Hospital Episode Statistics to develop an algorithm to aid early detection of IPAH – Sheffield Pulmonary Hypertension IndeX project (Bergemann et al Pulm Circ 2018.). We are currently in the process of validating such an algorithm.

Teaching Interests:

I currently provide lectures on the molecular and cellular mechanism of pulmonary hypertension, the use of pre-clinical models and pharmacogenomics on the following courses:

Professional Activities:

  • British Heart Foundation Project Grant Committee 2016-present
  • Scleroderma & Raynaud’s UK Research Committee, 2017-present
  • Editorial Board Member of Pulmonary Circulation, 2017-present
  • Grant Reviewer for MRC, Wellcome Trust, BBSRC, Heart Research UK
  • Manuscript Reviewer for the leading journals in the field including Nature, Journal of Clinical Investigation, Circulation, Circulations Research, ATVB, American Journal of Respiratory and Critical Care Medicine, European Respiratory Journal and Thorax.
  • Fellow of the Pulmonary Vascular Research Institute (PVRI).

Current Projects:

  • British Heart Foundation Senior Basic Science Research Fellow – Dec 2013 to Nov 2018. Defining cellular and molecular interactions in the OPG/TRAIL pathway in pulmonary arterial hypertension - £1,010,100. Allan Lawrie (PI).
  • British Heart Foundation Project Grant - Jul 2018 to Jun 2020. Investigating the sex-dependent role of macrophage subtypes in the pathogenesis of pulmonary arterial hypertension - £158,377. Allan Lawrie (PI), G. Millar, A.A.R. Thompson.
  • British Heart Foundation Project Grant - Dec 2017 to Nov 2019. The role of H3K27 methylation in vascular endothelial cell proliferation and function: Implications for pulmonary arterial hypertension - £193,282. S. John Wort (PI), Ian Adcock, Dongmin Shao, Allan Lawrie.
  • Wellcome Trust Clinical Research Career Development Fellowship to Dr Alexander Rothman - Nov 2017 to Feb 2020. Determining Novel SMURF1 Signalling Pathways and Precision Medicine Strategies in Patients with Pulmonary Arterial Hypertension - £460,409. (Research Supervisors: Sheila Francis, Allan Lawrie).
  • British Heart Foundation Intermediate Clinical Research Fellowship to Dr A. A. Roger Thompson – Sep 2018 to Aug 2022. The role of double-stranded RNA in pulmonary vascular remodelling - £722,505. (Research Supervisors: Ian Sabroe, Allan Lawrie).
  • British Heart Foundation Project Grant – Jun 2016 to May 2019. The disrupted hepcidin/ferroportin axis and proliferative responses in pulmonary arterial hypertension - £294,534. Gregory Quinlan (PI), S. John Wort, Allan Lawrie.

Publications:

For key publications see below. For a full list of publications click here.

Journal articles