Dr Margaret Rose Cunningham

Strathclyde Chancellor's Fellow

Strathclyde Institute of Pharmacy and Biomedical Sciences

Personal statement

Chancellor’s Fellow and Lecturer in Cardiovascular Pharmacology

My field of expertise is G protein-coupled receptor (GPCR)-dependent regulation of cardiovascular function with particular interest in proteinase-activated receptors (PARs) and purinergic receptor families.  My research involves investigating the molecular mechanisms of GPCR involvement in the processes that underpin platelet and vascular cell function and anti-cancer therapy-induced cardiotoxicity. In SIPBS, I co-lead the Cardiovascular and Metabolic Diseases research group with Dr Susan Currie.    

I am the Editor-in-Chief of Pharmacology Matters magazine and serve as a Reviewing Editor for Pharmacology Research & Perspectives (PR&P) journal.  I am an elected member of the RSE Young Academy of Scotland (YAS), a member of the Ingenious & Enterprising Women Network and a Winston Churchill Memorial Trust Fellow.  I am an Academy of Medical Sciences (AMS) springboard awardee and recently featured in their #MedSciLife Campaign. 

Improving attainment, participation and engagement in science is very important to me therefore I mentor postdoctoral researchers across the University, undergraduate students through the Strathclyde Cares Widening Access scheme and Secondary School students through the MCR pathways in West Dunbartonshire.  

I serve as Director of Outreach (in Biomolecular Sciences) with Dr Zahra Rattray (in Pharmacy) and I lead on the Career Progression working group on the SIPBS Athena SWAN Self-Assessment Team and additionally support the Organisation, Culture and Communication working group.          

Publications

P2Y1 and P2Y12 receptor heterodimerisation : from recombinant systems to native detection
Safar MA, Wood R, Cunningham MR, Kennedy C
British Journal of Pharmacology Vol 176, pp. 3049 (2019)
https://doi.org/10.1111/bph.14681
Assessment of adult rat cardiac fibroblast viability following chronic sunitinib treatment
McMullen Calum J, Wood Rachel A, Cunningham Margaret R, Currie Susan
Heart Vol 105, pp. A6-A7 (2019)
https://doi.org/10.1136/heartjnl-2019-SCF.13
P2Y1and P2Y12 receptor heterodimerisation : from recombinant systems to native detection
Safar Mohammed Adnan A, Wood Rachel Aimee, Tate Rothwelle, Cunningham Margaret Rose, Kennedy Charles
BPS-MPGPCR 2018 (2018)
P2Y1 and P2Y12 receptor heterodimerisation : from recombinant systems to native detection
Safar Mohammed Adnan A, Wood Rachel Aimee, Tate Rothwelle, Cunningham Margaret Rose, Kennedy Charles
BPS-MPGPCR 2018 (2018)
Heterodimerisation of purinergic GPCRs
Safar Mohammed Adnan A, Wood Rachel A, Cunningham Margaret R, Kennedy Charles
Molecular Neuropharmacology in Health and Wellbeing (2018)
CaMKIIδ interacts directly with IKKβ and modulates NF-kB signalling in adult cardiac fibroblasts
Martin Tamara P, McCluskey Claire, Cunningham Margaret R, Beattie James, Paul Andrew, Currie Susan
Cellular Signalling (2018)
https://doi.org/10.1016/j.cellsig.2018.07.008

more publications

Teaching

I am a Fellow of the Higher Education Academy (HEA) with a Postgraduate Diploma in Academic Practice.

I am class coordinator for BM434 Clinical Pharmacology and I lecture on the following undergraduate and postgraduate courses:

  • BM324 Fundamental Pharmacology
  • BM327 BABS 3 Pharmacology Labs
  • BM432 Research in Biomedical Sciences
  • BM933 Advanced studies in Haematology
  • BM906 Biomedical Sciences Project

 

I coordinate and deliver the Organisational and Staff Development Unit (OSDU) Research Bidding and Design - Getting Started course with Dr Katherine Duncan to help support early career researchers with grantmanship.   

Research interests

My research is highly collaborative and multidisciplinary with ongoing projects invested in understanding protein interacting pathways that regulate GPCR activity in cardiovascular system with the aim of identifying novel ways to target receptors for development of new therapies.  Investigations include the use of artificial intelligence in the design of small molecules that target GPCRs and the development of novel PAR modulators. Approaches used in our research include SILAC quantitative proteomics, cellular imaging of therapeutic agents using Mass Spectrometry Imaging (MSI) techniques, FRET, FRET-FLIM and meso-imaging.    

Current University of Strathclyde collaborators include:

  • Dr Susan Currie, SIPBS
  • Dr Blair Johnston, CMAC
  • Professor Gail McConnell, Physics
  • Professor Robin Plevin, SIPBS
  • Dr David Li, SIPBS
  • Dr Charles Kennedy, SIPBS

 

External collaborations include:

  • Professor Robert Liskamp, University of Glasgow, UK
  • Dr Matthew Harper, University of Cambridge, UK
  • Professor Stuart Mundell, University of Bristol, UK
  • Dr Patricia Martin, Glasgow Caledonian University, UK
  • Dr Christopher Nile, Glasgow Dental School, University of Glasgow, UK
  • Professor Atsufumi Kawabata, Kindai University, Japan
  • Atomwise Ltd, US

 

I have an open-door policy and offer a supportive environment for highly motivated students to progress in their studies and develop their research skills. 

  

 

Professional activities

Molecular Pharmacology of Emerging GPCR Therapeutic Targets
Organiser
17/12/2019
Ingenious Women Network Event:
Organiser
25/9/2019
Topic: Pharmacology of novel PAR antagonists in platelets
Invited speaker
12/9/2019
2019 Annual General Meeting of the Young Academy of Scotland
Participant
27/8/2019
Pharmacology Research & Perspectives (Journal)
Editor
20/8/2019
Cellular mechanisms of anti-cancer induced cardiotoxicity
Organiser
7/7/2019

more professional activities

Projects

Molecular mechanisms of HMGB1 release from platelets and its implication in chemotherapy-induced peripheral neuropathy and thrombosis
Domoto, Risa (Principal Investigator) Cunningham, Margaret Rose (Principal Investigator) Kawabata, Atsufumi (Co-investigator)
This project seeks to investigate the role of proteinase-activated receptors (PARs) in HMGB1-mediated platelet activity in response to thrombin. This will be followed by the study of chemotherapeutic influence on thrombin-mediated platelet HMGB1 release and any associated impact upon oxidized HMGB1 levels and platelet and vascular cell function.
01-Jan-2019 - 31-Jan-2020
Platelet connexins – Friend or Foe?
Cunningham, Margaret Rose (Principal Investigator) McGivern, Samantha-Joe (Researcher)
Research Interns @ Strathclyde (RI@S) scheme
24-Jan-2019 - 12-Jan-2019
Investigating the biomolecular complexity of drug-induced cardiotoxicity by fingerprinting single cell and cardiac spheroid mass spectral information using Time-of-flight Secondary Ion Mass Spectrometry (TOF-SIMS)
Cunningham, Margaret Rose (Principal Investigator) Veerman, Ben (Post Grad Student) Johnston, Blair (Co-investigator) Currie, Susan (Co-investigator)
The aim of this project is to significantly advance upon ongoing efforts in understanding drug-induced cardiotoxicity not only at the single cell level but in a multicellular model that may better reflect the cellular microenvironment of the heart. Extending studies to assess the metabolite changes in the multicellular environment in response to cancer therapeutics may reveal events integral to toxicity which may lead to new knowledge to develop ways to minimise or prevent cellular toxicity in the cardiac niche.
01-Jan-2019 - 28-Jan-2022
Investigating the off-target effects of the clinical trial candidate PZ-128
Cunningham, Margaret Rose (Principal Investigator) Brouck, Laurine (Researcher)
01-Jan-2018 - 29-Jan-2019
Investigating interplay between thrombin receptors and the molecular mechanism that lead to cancer therapy-associated platelet dysfunction
Cunningham, Margaret Rose (Principal Investigator) Sawyers, Lyn (Researcher)
01-Jan-2018 - 29-Jan-2019
Proteinase-activated receptor 4 (PAR4): a potential therapeutic target for the inhibition of thrombin-mediated cardiovasular activity
Cunningham, Margaret Rose (Principal Investigator) Cogan, Caitlin (Post Grad Student) Liskamp, Robert (Co-investigator)
Thrombin is a potent serine protease involved in regulating haemostasis and thrombosis during vascular injury. In response to vessel damage, release of thrombin into the circulation irreversibly activates a family of GPCRs called proteinase-activated receptors (PARs). PARs are expressed at the surface of platelets and in cells of the vessel wall (endothelial cells and smooth muscle cells - SMCs) where they promote platelet aggregation, endothelial angiogenesis, and SMC migration and proliferation respectively. Thrombin-mediated platelet activation and vascular inflammation occurs via PAR1 and PAR4, which make these receptors attractive therapeutic targets. The competitive PAR1 antagonist, Vorapaxar, has recently been FDA approved in the treatment of a limited cohort of patients suffering recurrent acute coronary syndromes (ACS). However, use of Vorapaxar has been restricted due to severity of bleeding resulting in the elevated risk of associated cerebral haemorrhage. It is clear that subtle approaches are required to combat the bleeding associated with antiplatelet therapies that target the thrombin pathway.

The hypothesis that this proposal is based upon is that targeting the thrombin/PAR4 axis and leaving thrombin/PAR1 activation intact is more effective in treating thrombosis and preserving haemostasis.

Project aim
The key aims are to understand the structure-function relationship of PAR4 and screen novel peptide-mimetic PAR4 modulators to assess their ability to:

i) Inhibit platelet activity
ii) Protect against thrombin-mediated vascular remodelling
01-Jan-2018 - 31-Jan-2019

more projects

Address

Strathclyde Institute of Pharmacy and Biomedical Sciences
Hamnett Wing

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