Professor Anthony Davenport

Role of apelin and 'orphan' G-protein coupled receptor systems in the human vasculature and their role in cardiovascular disease, novel agents for imaging atherosclerosis.

Function of G-protein coupled receptors in the human cardiovascular system in health and disease.

Repurposing existing medicines and discovery of novel compound blocking entry of SARS-CoV-2 via the angiotensin converting enzyme 2 (ACE2) pathway.

Director of Studies in Preclinical Medicine and Pharmacology

Professor of Cardiovascular Pharmacology

Anthony Davenport is Professor of Cardiovascular Pharmacology, University of Cambridge. He was previously British Heart Foundation Principal Scientist and for ten years held a BHF Science Lectureship.  He is a Fellow and active member of the British Pharmacological Society. In 2020 he was elected to an Honorary Fellowship of the Society in recognition of ‘sustained  excellence and leadership in science, healthcare, and public service’. He is also a Fellow of the Hypertension Society and International Fellow of the American Heart Association.  
He is a long standing executive member of the International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification, that maintains a data base of drugs and their targets at http://www.guidetopharmacology.org/.  He is also chair of the Endothelin Receptor Sub-committee, member of the International Scientific Advisory Board on Endothelin  and editor of 'Receptor binding Techniques'. He has held programme grants from the BHF and was co-applicant on three MRC programme grants to establish the multi-imaging facilities at Addenbrooke's Hospital.  From 2018 onwards, he has been identified as a Highly Cited Researcher, as determined by a citation analysis of Web of Science data, having produced multiple highly cited papers ranking in the top 1% by citations for a publication field and year.
In 2020, he was elected to the Council of the University of Cambridge, the principal executive and policy-making body of the University.
 

One third of all currently used medicines target a family of proteins called G-protein-coupled receptors (GPCRs), that respond to chemical messengers critical for normal signalling between cells but are also altered in many disease processes. New GPCRs have been identified following sequencing of the human genome but their function is not initially known. The aim of my research is to understand the role of GPCRs, together with their transmitters in the human cardiovascular system and how these are altered with disease, to identify new targets for novel drugs.

A second area of research is mapping the expression of proteins by human cells that are hijacked by the SARS-CoV-2 virus to enable entry into the host. The presence of a protein on the cell surface, ACE2 has emerged as being essential for the virus to bind in order to enter the patient’s tissues, such as the lungs and heart. The objective is to test medicines currently in use for other purposes, as well as new compounds, to test if they block entry of SARS-CoV-2 into human cells growing in the laboratory. Since the medicines are already in use, they have the potential to be tested in a clinical trial of patients with the virus, to see if entry is reduced.

• Harding SD, Armstrong JF, Faccenda E, Southan C, Alexander SPH, Davenport AP, Pawson AJ, Spedding M, Davies JA; NC-IUPHAR. (2020) IUPHAR/BPS guide to PHARMACOLOGY in 2022: curating pharmacology for COVID-19, malaria and antibacterials | Nucleic Acids Research | Oxford Academic (oup.com) Nucleic Acids Res. doi: 10.1093/nar/gkab1010. 
• Williams TL, Colzani MT, Macrae RGC, Robinson EL, Bloor S, Greenwood EJD, Zhan JR, Strachan G, Kuc RE, Nyimanu D, Maguire JJ, Lehner PJ, Sinha S, Davenport AP. (2021) Human embryonic stem cell-derived cardiomyocyte platform screens inhibitors of SARS-CoV-2 infection | Communications Biology (nature.com) Comm. Biol. 4:926. 
• Chapman FA, Nyimanu D, Maguire JJ, Davenport AP, Newby DE, Dhaun N. (2021) The therapeutic potential of apelin in kidney disease | Nature Reviews Nephrology Nat Rev Nephrol. 2021 doi: 10.1038/s41581-021-00461-z. 
• Robinson EL,   Alkass K,  Bergmann O, Maguire JJ,  Roderick HL,  Davenport AP. Genes Encoding ACE2, TMPRSS2 and Related Proteins Mediating SARS-CoV-2 Viral Entry are Upregulated with Age in Human Cardiomyocytes. (2020) Journal of Molecular and Cellular Cardiology; 18 Aug 2020
• Davenport AP, Scully CCG, de Graaf C, Brown AJH, Maguire JJ. (2020) Advances in therapeutic peptides targeting G protein-coupled receptors. Nat Rev Drug Discov.;19:389-413. 
• Alexander SPH, Armstrong JF, Davenport AP, Davies JA, Faccenda E, Harding SD, Levi-Schaffer F, Maguire JJ, Pawson AJ, Southan C, Spedding M. A rational roadmap for SARS-CoV-2/COVID-19 pharmacotherapeutic research and development: IUPHAR Review 29. (2020) Br J Pharmacol. 1-25.
• Ford TJ, Corcoran D, Padmanabhan S, Aman A, Rocchiccioli P, Good R, McEntegart M, Maguire JJ, Watkins S, Eteiba H, Shaukat A, Lindsay M, Robertson K, Hood S, McGeoch R, McDade R, Yii E, Sattar N, Hsu LY, Arai AE, Oldroyd KG, Touyz RM, Davenport AP, Berry C. (2020) Genetic dysregulation of endothelin-1 is implicated in coronary microvascular dysfunction. Eur Heart J. 
• Read C, Nyimanu D, Williams TL, Huggins DJ, Sulentic P, Macrae RGC, Yang P, Glen RC, Maguire JJ, Davenport AP. International Union of Basic and Clinical Pharmacology. CVII. Structure and Pharmacology of the Apelin Receptor with a Recommendation that Elabela/Toddler Is a Second Endogenous Peptide Ligand. (2019) Pharmacol Rev.;71:467-502. 10.1124/pr.119.017533.
• Yang P, Read C, Kuc RE, Buonincontri G, Southwood M, Torella R, Upton PD, Crosby A, Sawiak SJ, Carpenter TA, Glen RC, Morrell NW, Maguire JJ, Davenport AP. Elabela/Toddler Is an Endogenous Agonist of the Apelin APJ Receptor in the Adult Cardiovascular System, and Exogenous Administration of the Peptide Compensates for the Downregulation of Its Expression in Pulmonary Arterial Hypertension. Circulation. 2017;135:1160-73.
• Davenport AP, Hyndman KA, Dhaun N, Southan C, Kohan DE, Pollock JS, Pollock DM, Webb DJ, Maguire JJ. Endothelin. Pharmacol Rev. 2016;68(2):357-418. 10.1124/pr.115.011833.
• Irkle A, Vesey AT, Lewis DY, Skepper JN, Bird JL, Dweck MR, Joshi FR, Gallagher FA, Warburton EA, Bennett MR, Brindle KM, Newby DE, Rudd JH, Davenport AP. Identifying active vascular microcalcification by (18)F-sodium fluoride positron emission tomography. (2015) Nat Commun.;6:7495.
• Brevini, T, (…), Kuc, RE, (…), Williams, TJ, (…), Davenport, AP,  SampaziotisF (+74 authors) (2023)  FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2 Nature 615, 134–142 
• Abraham GR and Davenport  AP (2023) From ABCD to E for endothelin in resistant hypertension Cell, 186, 240-242
• Abraham, GR, DNyimanu, RE Kuc, Maguire, JJ, Davenport, APand SPHoole(2022) Trans-myocardial Extraction of Endothelin-1 Correlates with Increased Microcirculatory Resistance following Percutaneous Coronary Intervention, Journal of Interventional Cardiology: 9154048
• Macrae RGC, Colzani MT, Williams TL, Bayraktar S, Kuc RE, Pullinger AL, Bernard WG, Robinson EL, Davenport EE, Maguire JJ, Sinha S and Davenport AP (2022) Inducible apelin receptor knockdown reduces differentiation efficiency and contractility of hESC-derived cardiomyocytes Cardiovascular Research, 16:cvac065
• Abraham, GR, Kuc, RE, Althage, M, Greasley, PJ, Ambery, P, Maguire, JJ, Wilkinson, IB, Hoole, SP, Cheriyan, J, and Davenport, AP (2022) Endothelin-1 is increased in the plasma of patients hospitalised with Covid-19 Journal of Molecular and Cellular Cardiology, 167: 92–96
• Abraham, GR, Morrow, AJ, Oliveira, J, Weir-McCall, JR, Davenport, EE, Berry, C, Davenport, AP, & Hoole, SP (2022) Mechanistic study of the effect of Endothelin SNPs in microvascular angina - Protocol of the PRIZE Endothelin Sub-Study International Journal of Cardiology Heart and Vasculature, 39:100980
• Corovic A, (…), Davenport AP, (…) Tarkin MJ (+40 authors) Somatostatin Receptor PET/MR Imaging of Inflammation in Patients With Large Vessel Vasculitis and Atherosclerosis (2023) Journal of the American College of Cardiolology 81:336-54
• Williams TL, Strachan G, Macrae RGC, Kuc RE, Nyimanu D, Paterson AL, Sinha S, Maguire JJ and Davenport AP Differential expression in humans of the viral entry receptor ACE2 compared with the short deltaACE2 isoform lacking SARS-CoV-2 binding sites (2021) Scientific Report, 11:24336
• Nyimanu, D, Kay, RG, Kuc, KE, Brown, AJH, Gribble, FM, Maguire, JJ, Davenport AP (2021) In vitro metabolism of synthetic Elabela/Toddler (ELA-32) peptide in human plasma and kidney homogenates analyzed with mass spectrometry and validation of endogenous peptide quantification in tissues by ELISA Peptides, 145: 170642
• Read C, Nyimanu D, Yang, P, Kuc RE, Williams TL, Fitzpatrick, CM, Foster, R, Glen, RC, Maguire, JJ, Davenport, AP (2021) The G Protein Biased Small Molecule Apelin Agonist CMF-019 is Disease Modifying in Endothelial Cell Apoptosis In Vitro and Induces Vasodilatation Without Desensitisation In Vivo Frontiers in Pharmacology, 112242
• Owen NE, Nyimanu D, Kuc RE, Upton PD, Morrell NW, Alexander GJ, Maguire JJ, Davenport AP. (2021). Plasma levels of apelin are reduced in patients with liver fibrosis and cirrhosis but are not correlated with circulating levels of bone morphogenetic protein 9 and 10. Peptides. 136:170440
• Owen NE, Alexander GJ, Sen S, Bunclark K, Polwarth G, Pepke-Zaba J, Davenport AP, Morrell NW, Upton PD(2020) Reduced circulating BMP10 and BMP9 and elevated endoglin are associated with disease severity, decompensation and pulmonary vascular syndromes in patients with cirrhosis eBioMedicine, 56:102794
• Harding SD, Faccenda E, Southan C, Pawson AJ, Maffia P, Alexander SPH, Davenport AP, Fabbro D, Levi-Schaffer F, Spedding M, Davies JA (2020) The IUPHAR Guide to Immunopharmacology: connecting immunology and pharmacology Immunology160, 10-23
• Nyimanu, D, Kay, RG, Sulentic, P, Kuc, RE, Ambery, P, Jermutus, L Maguire, JJ, Reimann, F, Gribble, FM, Maguire, JJ, Davenport, AP (2019) Development and validation of an LC-MS/MS method for detection and quantification of in vivo derived metabolites of [Pyr1]apelin-13 in humans Peptides, 9,19934

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