Professor Philip E James

Job Title:            Professor of Cardiovascular Metabolism, Associate Dean (Research)
Room No: D211a        
Telephone No:  + 44 (0) 2920 417129
Email Address: PJames@cardiffmet.ac.uk

Research

Research Portfolio

I have authored 141 research publications to date the majority as primary or senior author, and present with a current overall H index of 27. This comprises 81 full papers in high-impact, peer-reviewed journals. I have also edited 1 research book and 6 chapters on methodology and Review texts. My work has also been published in the form of abstracts and commentaries (53, counting those in peer-reviewed journals only). The international quality of my outputs is further evidenced by my full inclusion in the Research Excellence Framework (REF) 2014, with four, 4* submissions

I have successfully gained a total research income of £3,262,042 of which £568,500 is currently active research, including a British Heart Foundation Project Grant, a NISCHR funded PhD Scholarship, and a Royal College of Physicians Fellowship (full details provided in cv).

The foundations and principles underpinning my approach to biomedical research were seeded during post-doctoral training and Associate Professor positions (Dartmouth Medical School, USA) where I built in-depth experience with techniques for measurement of oxygen, nitric oxide, and other radical species, and worked under the tutelage of Prof. Harold M Swartz, a pioneer in this research. During this apprenticeship I was awarded The Lubbers Award for outstanding contribution by a young scientist in the field.

I was recruited to Cardiff Medical School in 1999 to a Lectureship and the research opportunities afforded by being an integral part of the newly completed Wales Heart Research Institute. At this time I learnt of the concept that nitric oxide (NO), an important dilator of blood vessels, is not metabolised solely for excretion, but could be recycled from its key metabolites and subsequently utilised at sites remote from its production. I see this as a landmark moment in my research career because interest was sparked which features heavily in my current research. We built a team of scientists and clinicians to test the importance of this phenomenon in humans and soon featured amongst the leading laboratories worldwide in this field. I identified early disturbance in blood NO metabolism in diabetic patients, work that was a significant step in understanding the complex mechanisms contributing to small vessel disease in poorly controlled diabetes. The importance of tissue oxygen in controlling NO metabolism was soon appreciated; first to show release of NO from blood stores influences the venous circulation (with Prof M. Frenneaux, Norwich Medical School), and first to show interchange of NO metabolites across the heart in the human coronary circulation (Dr Vince Paul, St Georges; Dr R. Anderson, Cardiff).

I have more recently focused on the therapeutic administration of nitrite to induce vessel relaxation, and in particular whether nitrite can target NO to specific tissue areas that lack oxygen – work that has already received critical acclaim. This has been applied for relief of myocardial stress in Coronary Artery Disease (CAD) patients and we were the first to show potential therapeutic benefit in a patient cohort (Prof A. Fraser, Cardiff and Prof J. Halcox, Swansea). The majority of this work was funded by the British Heart Foundation, who funded my group as a "first in man" to study cardiac microvascular function and protection afforded by nitrite during coronary intervention (2011-2014).

The scientific aims of my research are driven by clinical impact. As an exemplar, in laboratory studies I discovered that anti-platelet drugs (thienopyridines) that are commonly used as the front line treatment in patients readily exhibit additional anti-platelet activity when mixed with nitrite. In small scale studies in patients we progressed these studies to find changes in CAD patients receiving nitrite, and these early findings are being expanded to investigate the potential therapeutic influence of enhancing nitrite longer term in the diet in CAD patients (Dr R. Anderson, Cardiff). A full-scale clinical trial is planned and could translate to significant improvement in CAD patient outcomes via a simple, cost effective dietary supplement. This forms the basis of a significant body of work and a potential impact-case study for REF2020 and beyond.

A centre of excellence for the measurement of NO has been established in Cardiff that is utilised by colleagues, collaborators, and industry worldwide. This culminated in my writing an invited review article recently on NO supplementation (Nitric Oxide Journal, special issue). In this capacity I have amassed a detailed knowledge base in this area and have accrued insight to both common findings and pitfalls; publications of note include methodological advances that have changed working practice and improved sensitivity issues in my lab and many others, and in the field of dietary supplementation and exercise enhancement working in both sedentary and elite athlete populations, with key collaborations with UK Sport, Science in Sport, and academic colleagues (for example, C. Easton, Glasgow and A, Tjonna, Norway). Outputs are published in high impact journals and projects are ongoing.  

The presence of a significant adipocyte-derived microvesicle population in human blood was recently discovered by my group, and this has ignited a new and exciting research direction which is funded to carry out in depth characterisation of adipocyte derived microvesicles (BHF funded project grant 2015-2018). I was intrigued by the observed association between visceral obesity and vascular disease. Although well-established clinically, little is known of the direct mechanistic links between adipose tissue and distal blood vessel disruption. I have set up key collaborations with national and international leaders and now boast methods in Cardiff that are available only in select laboratories worldwide. Utilising these techniques novel data is already accrued demonstrating circulating microvesicles in patients with metabolic syndrome imbalance and the effect of an acute treatment (lipid apheresis) in patients with familial hypercholesterolaemia. I am dedicated to driving this new program from Cardiff Metropolitan. To this end we now feature as a leading laboratory in the UK and have a recognised presence in the international field (ISEV). In particular, this work ties with the Cardiovascular Metabolism and Inflammation research group under the Cardiff Metropolitan Research Theme, Cardiovascular Health and Ageing.

Publications

1. Dietary Nitrate Supplementation and 3-weeks Sprint Interval Training Improves Flow Mediated Dilation in Healthy Males. Muggeridge DJ, Sculthorpe N, James PE, Easton C.
2. Med Sci Sports Exerc. 2016 May;48(5 Suppl 1):257. doi: 10.1249/01.mss.0000485775.36248.31. 
3. The effects of dietary nitrate supplementation on the adaptations to sprint interval training in previously untrained males. Muggeridge DJ, Sculthorpe N, James PE, Easton C.
4. J Sci Med Sport. 2016 May 21. pii: S1440-2440(16)30063-9. doi: 10.1016/j.jsams.2016.04.014. [Epub ahead of print]
5. Dietary nitrate increases exercise tolerance in patients with non-ischemic, dilated cardiomyopathy-a double-blind, randomized, placebo-controlled, crossover trial. Kerley CP, O'Neill JO, Reddy Bijjam V, Blaine C, James PE, Cormican L. J Heart Lung Transplant. 2016 Jul;35(7):922-6. doi: 10.1016/j.healun.2016.01.018. 
6. Characterisation of adipocyte-derived extracellular vesicles released pre- and post-adipogenesis. Connolly KD, Guschina IA, Yeung V, Clayton A, Draman MS, Von Ruhland C, Ludgate M, James PE, Rees DA. J Extracell Vesicles. 2015 Nov 24;4:29159. doi: 10.3402/jev.v4.29159.
7. Changes in platelet function independent of pharmacotherapy following coronary intervention in non-ST-elevation myocardial infarction patients. Freeman PM, Moschonas KE, Hinz C, O'Donnell VB, Kinnaird TD, James PE, Anderson RA. Atherosclerosis. 2015 Nov;243(1):320-7. doi: 10.1016/j.atherosclerosis.2015.09.024.
8. Nitrate pharmacokinetics: Taking note of the difference. James PE, Willis GR, Allen JD, Winyard PG, Jones AM. Nitric Oxide. 2015 Aug 1;48:44-50. doi: 10.1016/j.niox.2015.04.006.
9. Sport-Specific Physiological Adaptations in Highly Trained Endurance Athletes.
10. Lundgren KM, Karlsen T, Sandbakk Ø, James PE, Tjønna AE. Med Sci Sports Exerc. 2015 Oct;47(10):2150-7. doi: 10.1249/MSS.0000000000000634.
11. A new mechanism of action of thienopyridine antiplatelet drugs - a role for gastric nitrosthiol metabolism? Anderson RA, Bundhoo S, James PE. Atherosclerosis. 2014 Nov;237(1):369-73. doi: 10.1016/j.atherosclerosis.2014.08.045.
12.  Systemic oxidative-nitrosative-inflammatory stress during acute exercise in hypoxia; implications for microvascular oxygenation and aerobic capacity. Woodside JD, Gutowski M, Fall L, James PE, McEneny J, Young IS, Ogoh S, Bailey DM. Exp Physiol. 2014 Dec 1;99(12):1648-62. doi: 10.1113/expphysiol.2014.081265.
13.  Young women with polycystic ovary syndrome have raised levels of circulating annexin V-positive platelet microparticles. Willis GR, Connolly K, Ladell K, Davies TS, Guschina IA, Ramji D, Miners K, Price DA, Clayton A, James PE, Rees DA. Hum Reprod. 2014 Dec;29(12):2756-63. doi: 10.1093/humrep/deu281.