Associate Lecturer in Medicine, University of Cambridge

Consultant Physician and Clinical Pharmacologist, Cambridge University Hospitals NHS Foundation Trust.

Director of the Cardiovascular Clinical Trials Office, Cambridge University Hospitals NHS Foundation Trust.

Vice Chair, Cambridge Central Ethics Committee, Health Research Authority.

Email:  jc403@cam.ac.uk

Tel: 01223 256653

Website:Â http://www.cambsems.org

Research and Academic Interests

My research focuses on vascular function and inflammation, NO bioavailability and vascular-ventricular interactions. I have a keen interest in identifying novel agents that may improve vascular health, as measured in vivo, in human models of health and disease.

I am the only MHRA accredited Phase 1 first-in-human physician on the Cambridge Biomedical Campus working in the University/NHS domains since 2006.

Vascular function and inflammation

We use well-described models to characterise this in our Department as well as more experimental approaches to stratify patients. These include forearm plethysmography, flow mediated dilatation and arterial stiffness as well as a range of haemodynamic and circulatory measurements. These biomarkers enable us to understand the mechanisms underlying the improvement or deterioration in vascular health in vivo from an NO bioavailability viewpoint, provide proof of concept of human physiology and pathophysiology and also help interrogate the role of various peptides and hormones in the regulation of vascular tone. The strength of these unique types of clinical physiological studies lies in their direct relevance to human biology, occasionally confirming pre-clinical models, but simultaneously providing relevance to human pathophysiology.

We are also interested in developing more novel approaches to understanding vascular pathophysiology using non-invasive imaging and bespoke technologies to understand angiogenesis. These techniques may be applied to human physiological studies and clinical trials of investigational medicinal products. This enables the translation of pre-clinical models of novel therapeutic agents into niche products differentiating an investigational medicinal product from existing therapies, or providing proof of mechanism in order to progress such a product through the stages of clinical drug development. For example, building on some seminal work performed by local collaborators, we have used FDG PET-CT in a novel experimental medicine study to understand the effects of a new therapeutic agent in altering the biology of atherosclerosis. We have applied similar techniques to assess existing therapies for patients with chronic inflammatory conditions, to understand if they possess off-target pharmacology which may improve outcomes as an inadvertent benefit of therapy. Along similar lines, we are aiming to understand how new drugs may disrupt vascular networks in the microcirculatory environment by examining the effects of such therapies on conjunctival vessels.

Phase 1/2 and First in human clinical trials in cardiovascular disease

We have an active programme of work in early phase studies in the cardiovascular arena. This includes repurposing of currently licensed drugs for novel indications where they are currently contraindicated, or in the execution of first in human trials in conjunction with the GSK Clinical Unit based on the campus.

Most early phase studies now embed proof of mechanism and proof of concept pharmacodynamic markers in their trials to discharge risks and provide evidence of benefit.

We also work closely with other industrial partners on pre-competitive and early phase conceptual studies to provide evidence of target engagement.

Cardiovascular Trials Office

I direct the Cardiovascular Trials Office of the Cambridge Clinical Trials Unit which leads the design, implementation and delivery of clinical trials on campus. This includes experimental studies in the cardio-respiratory arena in keeping with the Biomedical Research Centre theme.

Teaching

I lead an active programme of educational programmes for junior doctors and medical students. This includes the Cambridge Medical Seminars (http://cambsems.org ) and the Experimental Medicine Training Initiative (http://www.emi-training.org) for doctoral clinical/non-clinical students. This programme of education is set to be expanded internationally in 2018 with courses in SE Asia.

Recent Publications

• Mukhtar O, Cheriyan J, Cockcroft JR, Collier D, Coulson JM, Dasgupta I, Faconti L, Glover M, Heagerty AM, Khong TK, Lip GYH, Mander AP, Marchong MN, Martin U, McDonnell BJ, McEniery CM, Padmanabhan S, Saxena M, Sever PJ, Shiel JI, Wych J, Chowienczyk PJ, Wilkinson IB. A randomized controlled crossover trial evaluating differential responses to antihypertensive drugs (used as mono- or dual therapy) on the basis of ethnicity: The comparIsoN oF Optimal Hypertension RegiMens; part of the Ancestry Informative Markers in HYpertension program-AIM-HY INFORM trial. Am Heart J. 2018 May 20;204:102-108. doi: 10.1016/j.ahj.2018.05.006. [Epub ahead of print]
• Fisk M, Cheriyan J, Mohan D, McEniery CM, Forman J, Cockcroft JR, Rudd JHF, Tal-Singer R, Hopkinson NS, Polkey MI, Wilkinson IB. Vascular inflammation and aortic stiffness: potential mechanisms of increased vascular risk in chronic obstructive pulmonary disease. Respir Res. 2018 May 24;19(1):100. doi: 10.1186/s12931-018-0792-1.
• Mohan D, Forman JR, Allinder M, McEniery CM, Bolton CE, Cockcroft JR, MacNee W, Fuld J, Marchong M, Gale NS, Fisk M, Nagarajan S, Cheriyan J, Lomas DA, Calverley PMA, Miller BE, Tal-Singer R, Wilkinson IB, Polkey MI; ERICA Consortium. Fibrinogen does not relate to cardiovascular or muscle manifestations in COPD: cross-sectional data from the ERICA study. Thorax. 2018 Apr 4. pii: thoraxjnl-2018-211556. doi: 10.1136/thoraxjnl-2018-211556. [Epub ahead of print]
• Fisk M, Cheriyan J, Mohan D, Forman J, Mäki-Petäjä KM, McEniery CM, Fuld J, Rudd JHF, Hopkinson NS, Lomas DA, Cockcroft JR, Tal-Singer R, Polkey MI, Wilkinson IB. The p38 mitogen activated protein kinase inhibitor losmapimod in chronic obstructive pulmonary disease patients with systemic inflammation, stratified by fibrinogen: A randomised double-blind placebo-controlled trial. PLoS One. 2018 Mar 22;13(3):e0194197. doi: 10.1371/journal.pone.0194197. eCollection 2018.
• Fisk M, McEniery CM, Gale N, Mäki-Petäjä K, Forman JR, Munnery M, Woodcock-Smith J, Cheriyan J, Mohan D, Fuld J, Tal-Singer R, Polkey MI, Cockcroft JR, Wilkinson IB; ERICA Consortium and ACCT Investigators. Surrogate Markers of Cardiovascular Risk and Chronic Obstructive Pulmonary Disease: A Large Case-Controlled Study. Hypertension. 2018 Mar;71(3):499-506. doi: 10.1161/HYPERTENSIONAHA.117.10151. Epub 2018 Jan 22.
• Coello C, Fisk M, Mohan D, Wilson FJ, Brown AP, Polkey MI, Wilkinson I, Tal-Singer R, Murphy PS, Cheriyan J, Gunn RN. Quantitative analysis of dynamic ¹⁸F-FDG PET/CT for measurement of lung inflammation. EJNMMI Res. 2017 Dec;7(1):47. doi: 10.1186/s13550-017-0291-2. Epub 2017 May 25.
• Yang P, Kuc RE, Brame AL, Dyson A, Singer M, Glen RC, Cheriyan J, Wilkinson IB, Davenport AP, Maquire JJ. [Pyr1]Apelin-13(1-12) Is a Biologically Active ACE2 Metabolite of the Endogenous Cardiovascular Peptide [Pyr1]Apelin-13. Front Neurosci 2017 Feb 28;11:92. doi: 10.3389/fnins.2017.00092. eCollection 2017.
• Chen DL, Cheriyan J, Chilvers ER, Choudhury G, Coello C, Connell M, Fisk M, Groves AM, Gunn RN, Holman BF, Hutton BF, Lee S, MacNee W, Mohan D, Parr D, Subramanian D, Tal-Singer R, Thielemans K, van Beek EJ, Vass L, Wellen JW, Wilkinson I, Wilson FJ. Quantification of Lung PET Images: Challenges and Opportunities. J Nucl Med 2017 Feb;58(2):201-207. doi: 10.2967/jnumed.116.184796. Epub 2017 Jan 12.
• Yang L, Cheriyan J, Gutterman DD, Mayer RJ, Ament Z, Griffin JL, Lazaar AL, Newby DE, Tal-Singer R, Wilkinson IB. Mechanisms of Vascular Dysfunction in COPD and Effects of a Novel Soluble Epoxide Hydrolase Inhibitor in Smokers. Chest 2017 Mar;151(3):555-563. doi: 10.1016/j.chest.2016.10.058. Epub 2016 Nov 21.
• Mäki-Petäjä KM, Barrett SM, Evans SV, Cheriyan J, McEniery CM, Wilkinson IB.  Hypertension. 2016 Nov;68(5):1290-1297. Epub 2016 Sep 26. The Role of the Autonomic Nervous System in the Regulation of Aortic Stiffness.
• Mäki-Petäjä KM, Day L, Cheriyan J, Hall FC, Östör AJ, Shenker N, Wilkinson IB.  J Am Heart Assoc. 2016 Feb 19;5(2). pii: e002762. doi: 10.1161/JAHA.115.002762. Tetrahydrobiopterin supplementation improves endothelial function but does not alter aortic stiffness in patients with rheumatoid arthritis.
• Lazaar AL¹, Yang L², Boardley RL³, Goyal NS¹, Robertson J³, Baldwin SJ³, Newby DE⁴, Wilkinson IB², Tal-Singer R¹, Mayer RJ¹, Cheriyan J^2, Pharmacokinetics, pharmacodynamics and adverse event profile of GSK2256294, a novel soluble epoxide hydrolase inhibitor.
• Brame AL, Maguire JJ, Yang P, Dyson A, Torella R, Cheriyan J, Singer M, Glen RC, Wilkinson IB, Davenport AP. Design, characterization, and first-in-human study of the vascular actions of a novel biased apelin receptor agonist. Hypertension 2015 April 4
• Yang L, Mäki-Petäjä K, Cheriyan J, McEniery C, Wilkinson IB. The role of epoxyeicosatrienoic acids in the cardiovascular system.
• Serg M, Graggabar J, Kampus P, Zagura M, Kals J, Mäki-Petäjä KM, Cheriyan J, Zilmer M, Eha J,  McEniery CM, Wilkinson IB. Value of haemodynamic profiling to the response of antihypertensive therapy. Artery Research Journal 2014 August 26
• Fisk M, Gajendragadkar PR, Mäki-Petäjä KM, Wilkinson IB, Cheriyan J. Therapeutic potential of p38 MAP kinase inhibition in the management of cardiovascular disease. Am J Cardiovasc Drugs. 2014 Jun 14
• Gajendragadkar PR, Hubsch A, Mäki-Petäjä KM, Serg M, Wilkinson IB, Cheriyan J. Effects of oral lycopene supplementation on vascular function in patients with cardiovascular disease and healthy volunteers: a randomised controlled trial. PloS One 2014 Jun 9.
• Barbour AM, Sarov-Blat L, Cai G, Fossler MJ, Sprecher DL, Graggaber J, McGeoch AT, Maison J, Cheriyan J. Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Losmapimod following a Single Intravenous or Oral Dose in Healthy Volunteers. Br J Clin Pharmacol2012 Dec 7. [Epub ahead of print]
• Mäki-Petäjä KM, Elkhawad M, Cheriyan J, Joshi FR, Ostör AJ, Hall FC, Rudd JH, Wilkinson IB.
  Anti-tumor necrosis factor-α therapy reduces aortic inflammation and stiffness in patients with rheumatoid arthritis.Circulation2012 Nov 20;126(21):2473-80.
• Pucci G, Cheriyan J, Hubsch A, Hickson SS, Gajendragadkar PR, Watson T, O’Sullivan M, Woodcock-Smith J, Schillaci G, Wilkinson IB, McEniery CM.
  Evaluation of the Vicorder, a novel cuff-based device for the noninvasive estimation of central blood pressure. J Hypertens2013 Jan;31(1):77-85.
• Elkhawad M, Rudd JH, Sarov-Blat L, Cai G, Wells R, Davies LC, Collier DJ, Marber MS, Choudhury RP, Fayad ZA, Tawakol A, Gleeson FV, Lepore JJ, Davis B, Willette RN, Wilkinson IB, Sprecher DL, Cheriyan J.
  Effects of p38 mitogen-activated protein kinase inhibition on vascular and systemic inflammation in patients with atherosclerosis. JACC Cardiovasc Imaging 2012 Sep;5(9):911-22.
• Cheriyan J, Webb AJ, Sarov-Blat L, Elkhawad M, Wallace SM, Mäki-Petäjä KM, Collier DJ, Morgan J, Fang Z, Willette RN, Lepore JJ, Cockcroft JR, Sprecher DL, Wilkinson IB.
  Inhibition of p38 Mitogen-Activated Protein Kinase Improves Nitric Oxide-Mediated Vasodilatation and Reduces Inflammation in Hypercholesterolemia. Circulation 2011 Feb 8;123(5):515-23. Epub 2011 Jan 24.
• Wallace SM, Mäki-Petäjä KM, Cheriyan J, Davidson EH, Cherry L, McEniery CM, Sattar N, Wilkinson IB, Kharbanda RK.
  Simvastatin prevents inflammation-induced aortic stiffening and endothelial dysfunction. Br J Clin Pharmacol 2010 Dec;70(6):799-806.
• Cheriyan J, Burton TJ, Bradley TJ, Wallace SM, Mäki-Petäjä KM, Mackenzie IS, McEniery CM, Brown J, Wilkinson IB.
  The effects of urotensin II and urantide on forearm blood flow and systemic haemodynamics in humans.Br J Clin Pharmacol2009 Oct;68(4):518-23.
• Hickson SS, Butlin M, Mir FA, Graggaber J, Cheriyan J, Khan F, Grace AA, Yasmin, Cockcroft JR, Wilkinson IB, McEniery CM; Anglo-Cardiff Collaboration Trial Investigators.
  The accuracy of central SBP determined from the second systolic peak of the peripheral pressure waveform. J Hypertens 2009 Sep;27(9):1784-8.
• Mäki-Petäjä KM, Cheriyan J, Booth AD, Hall FC, Brown J, Wallace SM, Ashby MJ, McEniery CM, Wilkinson IB.
  Inducible nitric oxide synthase activity is increased in patients with rheumatoid arthritis and contributes to endothelial dysfunction. Int J Cardiol 2008 Oct 13;129(3):399-405. Epub 2008 Jun 20.
• Cheriyan J, Wilkinson IB.
  Role of increased aortic stiffness in the pathogenesis of heart failure.
  Curr Heart Fail Rep 2007 Sep;4(3):121-6. Review.
• Mackenzie IS, Maki-Petaja KM, McEniery CM, Bao YP, Wallace SM, Cheriyan J, Monteith S, Brown MJ, Wilkinson IB.
  Aldehyde dehydrogenase 2 plays a role in the bioactivation of nitroglycerin in humans. Arterioscler Thromb Vasc Biol 2005 Sep;25(9):1891-5. Epub 2005 Jul 28.
• J Cheriyan, CM McEniery and IB Wilkinson. Oxford Specialist Handbook in Hypertension. Oxford University Press 2010. ISBN 9780199229550.
• Cheriyan J, O’Shaughnessy KM, Brown MJ. Primary Prevention of CVD: treating hypertension. BMJ Clinical Evidence. ISSN 1752-8526. Copyright BMJ Publishing Group Limited 2010.