Professor Allan Lawrie

BSc, PhD

Department of Infection, Immunity and Cardiovascular Disease

Professor of Translational Cardiopulmonary Science

British Heart Foundation Senior Basic Science Research Fellow

Director, Donald Heath Research Programme in Pulmonary Hypertension

a.lawrie@sheffield.ac.uk
+44 114 215 9536

Full contact details

Professor Allan Lawrie
Department of Infection, Immunity and Cardiovascular Disease
The Medical School
Beech Hill Road
Sheffield
S10 2RX
Profile

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 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, biomarkers, novel therapies, and the use of ‘Real-World’ data including NHS HES and personal activity data to improve early disease diagnosis and monitoring of treatment response.

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 (Arnold et al Nat Comms 2019).

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 (Chen et al Circ 2018).


Biomarkers and Precision Medicine for Pulmonary Arterial Hypertension

I am Chief Investigator for The Sheffield Teaching Hospitals Observational Study of Patients with Pulmonary Hypertension, Cardiovascular and other Respiratory Diseases (STH-ObS). Through STH-Obs we have developed a biobank of samples from patients with Pulmonary Hypertension and other cardiovascular and respiratory disease (DNA/RNA/Plasma/Serum/Urine). I have a strong interest in the development of multi-omic signatures of disease as biomarkers (proteomic, miRNA and epigenetic), an integrating these biological signals with clinical phenotype to discover novel disease mechanisms.

To this end I have established national and international collaborations resulting in a number of high profile studies including whole genome sequencing (Gräf et al Nat. Comms 2018), RNA expression (Rhodes et al AJRCCM 2020), miRNA (Rhodes et al AJRCCM 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 and treatment response

Working with our partner IQVIA Ltd we are exploring the potential to harnessing real-world healthcare resource utilisation data in the form of NHS Hospital Episode Statistics to develop an algorithm to aid early detection of PAH (Bergemann et al Pulm Circ 2018 & 2019).

Most recently working with Euan Ashley (Stanford) I am exploring the use of personal activity data and the use of the MyHeart Counts App in STH-Obs to assess treatment response in PAH, and monitor signs of early cardio/respiratory disease.


Current projects

  • British Heart Foundation Senior Basic Science Research Fellow (renewal) – Dec 2018 to Nov 2023. Defining the molecular mechanisms of the OPG-FAS-TRAIL axis in pulmonary arterial hypertension - £842,732. Allan Lawrie (PI).
  • British Heart Foundation Special Project Grant (renewal) – Jan 2019 to Dec 2023. National cohort study of idiopathic and heritable pulmonary arterial hypertension £1,502,821. Co-I, PI – Nick Morrell, Cambridge.
  • British Heart Foundation Project Grant - Jul 2018 to Dec 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.
  • 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).
Publications

Show: Featured publications All publications

Journal articles

All publications

Journal articles

Chapters

  • Hickey PM, Condliffe R, Lawrie A & Kiely DG (2018) Pulmonary Hypertension, Foundations of Respiratory Medicine (pp. 315-330). Springer International Publishing RIS download Bibtex download

Conference proceedings papers

Patents

  • Wharton SP & Higenbottam TW (2001) Pulmonary hypertension. Appl. 01 Jan 2001. RIS download Bibtex download

Other

Research group

PhD Students

  • Nur Nabila Abu Bakar
  • Adam Briathwaite (Donald Heath Studentship)
  • Peter Hickey (Donald Heath Clinical Training Fellow)
  • Jianhui Lin (UoS/Tongji Studentship)

Group Members

  • Nadine Arnold, Senior Scientific Officer
  • Dr Josephine Pickworth, Post-doctoral Research Associate
  • Dr Laura West, Post-doctoral Research Associate
  • Dr Amira Zawia, Post-doctoral Research Associate
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 2016-2020.
  • 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).
  • Organising committee for the scientific programme at the PVRI 2021 Annual World Congress.