51³Ô¹ÏÍø

Caroline is an internationally recognised expert in vascular cell signalling and biology with 20 years’ experience in the field. Her laboratory specialises in investigating the functional relevance of molecular signalling pathways in human and animal endothelial cells and a range of other vascular cell types. She is particularly known for her work on mechanisms of vascular endothelial eicosanoid generation and recent studies have identified biological roles for novel fatty acid metabolites in vascular repair and angiogenesis. She was awarded a competitive British Heart Foundation (BHF) Fellowship which launched her independent research career and her work has since been supported by grants and studentships from the BBSRC, the Wellcome Trust, the BHF, Diabetes UK, Heart Research UK and through collaborative ventures with industry (currently Unilever and Novartis). She co-ordinated the Comparative Physiology and Medicine reserach programme for 3 years (2009-2012) Caroline’s major research interest is in endothelial cell signalling. Her research group (funded by the BBSRC, The Wellcome Trust and the British Heart Foundation) is investigating the molecular mechanisms important for regulating pro- and anti-inflammatory gene expression and downstream cellular functions in response to a range of external stimuli, including ligands for G protein-coupled receptors and growth factor receptors, and exogenous lipoproteins. The group uses in vitro, ex vivo and in vivo cell and molecular approaches to delineate the signalling pathways controlling gene expression and functional responses of human and murine large vessel and microvascular endothelial cells.Caroline was an associate editor of the Biochemical Journal for over 10 years and is a founder member of the European Vascular Biology Organisation and of the London Vascular Biology Forum. She reviews extensively for a number of UK grant giving bodies (BBSRC, BHF, Wellcome Trust, MRC and others) and for European bodies (Netherlands, Ireland, Austria MRC equivalents). She has supervised over 20 PhD students and has examined 30 PhD theses.

Research Interests: focus is primarily on vascular cell function with emphasis on understanding molecular control mechanisms. Current projects cover: Lipoprotein- and GPCR-mediated regulation of endothelial, vascular smooth muscle, progenitor and immune cell function; Regulation of cyclo-oxygenase expression and roles of lipid mediators in angiogenesis, fibrosis and calcification; Pathophysiological roles of GPCRs in the cardiovascular system with a focus on protease-activated receptors; lipid- and inflammation-mediated insulin resistance in skeletal muscle and vasculature.

Example publications:

Faulkner A, Lynam E, Purcell R, Jones C, Lopez C, Board M, Wagner KD, Wagner N, Carr C, Wheeler-Jones C.
 
Sci Rep. 2020 May 12;10(1):7849. doi: 10.1038/s41598-020-63900-0 

Patel, J J; Bourne, L E; Davies, B K; Arnett, T R; MacRae, V E; Wheeler-Jones, C P D; Orriss, I R.

Experimental Cell Research, 380;1:100-113. 2019

Al-Rashed F, Calay D, Lang M, Thornton CC, Bauer A, Kiprianos A, Haskard DO, Seneviratne A, Boyle JJ, Schonthal AH, Wheeler-Jones CP, Mason JC.
Celecoxib exerts protective effects in the vascular endothelium via COX-2-independent activation of AMPK-CREB-Nrf2 signalling.
Sci Rep.  8(1):6271, 2018.

Vara D, Watt JM, Fortunato TM, Mellor H, Burgess M, Wicks K, Mace K, Reeksting S, Lubben A, Wheeler-Jones CPD, Pula G. Direct Activation of NADPH Oxidase 2 by 2-Deoxyribose-1-Phosphate Triggers Nuclear Factor Kappa B-Dependent Angiogenesis. Antioxid Redox Signal. 28(2):110-130, 2018.

Lawson JS, Liu HH, Syme HM, Purcell R, Wheeler-Jones CPD*, Elliott J*. *equal contribution. The cat as a naturally occurring model of renal interstitial fibrosis: Characterisation of primary feline proximal tubular epithelial cells and comparative pro-fibrotic effects of TGF-β1. PLoS One. 13(8):e0202577, 2018.

LAWSON, J S; SYME, H M; WHEELER-JONES, CPD; ELLIOTT, J

BMC Veterinary Research, 14; 76. (2018)

Jonas KC, Melrose T, Thompson IR, Baxter GF, Lipscomb VJ, Niessen SJ, Lawson C, McArdle CA, Roberson MS, McGonnell IM, Wheeler-Jones CP, Fowkes RC. Natriuretic peptide activation of extracellular regulated kinase 1/2 (ERK1/2) pathway by particulate guanylyl cyclases in GH3 somatolactotropes. Cell Tissue Res. 369(3):567-578, 2017.

Latham Birt SH, Purcell R, Botham KM, Wheeler-Jones CPD. Endothelial HO-1 induction by model TG-rich lipoproteins is regulated through a NOX4-Nrf2 pathway. J Lipid Res. 57: 1204-18, 2016.

Lawson JS, Syme HM, Wheeler-Jones CP, Elliott J. Urinary active transforming growth factor β in feline chronic kidney disease. Vet J. 214: 1-6, 2016.

Lawson JS, Elliott J, Wheeler-Jones C, Syme H, Jepson R. Renal fibrosis in feline chronic kidney disease: known mediators and mechanisms of injury. Vet J. 203(1):18-26, 2015.

Faulkner A, Purcell R, Hibbert A, Latham S, Thomson S, Hall W, Wheeler-Jones CPD* & David Bishop-Bailey* *co-senior. Thin layer angiogenesis: a modified basement matrix assay for assessment of endothelial cell differentiation. BMC Biol 15: 41, 2014.

Talbot N, Wheeler-Jones CPD and Cleasby M. Palmitoleic acid prevents palmitic acid-induced macrophage activation and consequent p38 MAPK-mediated skeletal muscle insulin resistance. Mol Cell Endocrinol 393: 129-142, 2014.

Tivers MS, House AK, Smith KC, Wheeler-Jones CP, Lipscomb VJ. Markers of angiogenesis associated  with surgical attenuation of congenital portosystemic shunts in dogs. J Vet Intern Med. 28(5):1424-32. 2014.

Purcell R, Latham S, Botham KM, Hall WH and Wheeler-Jones CPD. High-fat meals rich in EPA plus DHA versus DHA only have differential effects on postprandial lipemia and plasma 8-isoprostane F2α concentrations compared to a control high-oleic acid meal: a randomized controlled trial. Am J Clin Nutr 100: 1019-1028, 2014.

Fortunato T, Vara D, Wheeler-Jones C* and Pula G*. Expression of protease-activated receptor 1 and 2 and anti-vasculogenic activity of PAR1 in human endothelial colony-forming cells. PLoS ONE 9: e109375, 2014. *co-senior.

Wheeler-Jones CP, Clarkin CE, Farrar CE, Dhadda P, Chagastelles P, Nardi N, Jones PM. Endoglin (CD105) is not a specific selection marker for endothelial cells in human islets of Langerhans. Diabetologia 56, 222-224, 2013.

Clarkin CE, King A, Chagastelles P, Nardi N, Wheeler-Jones CPD* and Jones PM*. ALK5 inhibition reverses impairment of islet endothelial cell viability by endogenous mesenchymal stromal cells. Stem Cells. 31, 547-59, 2013 *co-senior

GRAHAM VS, LAWSON C, WHEELER-JONES CP, PERONA JS, RUIZ-GUTIERREZ V, BOTHAM KM. (2012)
Triacylglycerol-rich lipoproteins derived from healthy donors fed different olive oils modulate cytokine secretion and cyclooxygenase-2 expression in macrophages: the potential role of oleanolic acid. Eur J Nutr 51(3):301-9.

GARONNA E, BOTHAM KM, BIRDSEY GM, RANDI AM, GONZALEZ-PEREZ RR AND WHEELER-JONES CPD (2011)
Vascular endothelial growth factor receptor-2 couples cyclo-oxygenase-2 with pro-angiogenic actions of leptin on human endothelial cells. PLoS ONE 6, e18823, 2011.

CLARKIN CE, ALLEN S, KUIPER NJ, WHEELER BT, WHEELER-JONES CP, PITSILLIDES AA (2011).
Regulation of UDP-glucose dehydrogenase is sufficient to modulate hyaluronan production and release, control sulfated GAG synthesis, and promote chondrogenesis. J Cell Physiol 226(3):749-61.

CLARKIN CE, ALLEN S, WHEELER-JONES CP, BASTOW ER, PITSILLIDES AA. (2011).
Reduced chondrogenic matrix accumulation by 4-methylumbelliferone reveals the potential for selective targeting of UDP-glucose dehydrogenase. Matrix Biol. 30(3):163-8.

GRAHAM VS, DI MAGGIO P, ARMENGOL S, LAWSON C, WHEELER-JONES CP, BOTHAM KM (2011)
Inhibition of macrophage inflammatory cytokine secretion by chylomicron remnants is dependent on their uptake by the low density lipoprotein receptor. Biochim Biophys Acta 1811(3):209-20.

BENTLEY C, HATHAWAY N, WIDDOWS J, BEJTA F, DE PASCALE C, AVELLA M, WHEELER-JONES CP, BOTHAM KM, LAWSON C. (2011).
Influence of chylomicron remnants on human monocyte activation in vitro. Nutr Metab Cardiovasc Dis. 21(11):871-8.

PULA G, GARONNA E, DUNN WB, HIRANO M, PIZZORNO G, CAMPANELLA M, SCHWARTZ EL, EL KOUNI MH AND WHEELER-JONES CPD. (2010).
Paracrine stimulation of endothelial cell motility and angiogenesis by platelet-derived deoxyribose-1-phosphate. Arterioscler Thromb Vasc Biol. 30(12):2631-8.

WHEELER-JONES CPD, FARRAR CE AND PITSILLIDES AA. (2010).
The hyaluronan-rich endothelial glycocalyx: a target for therapeutic intervention? Curr Opin Investig Drugs 11(9):997-1006.

DALLA-RIVA J, GARONNA E, ELLIOTT J, BOTHAM KM AND WHEELER-JONES CPD. (2010).
Endothelial cells as targets for chylomicron remnants. Atheroscler Suppl. 11(1):31-37.

HAMDULAY SS, WANG B, BIRDSEY GM, ALI F, DUMONT O, EVANS PC, HASKARD DO, WHEELER-JONES CP*, MASON JC*. (2010).
Celecoxib activates PI-3K/Akt and mitochondrial redox signaling to enhance heme oxygenase-1-mediated anti-inflammatory activity in vascular endothelium. Free Radic Biol Med. 48(8):1013-1023, *equal contribution.

WHEELER-JONES, CPD, FARRAR, C, GARONNA, E. (2009).
Protease-activated receptors, cyclo-oxygenases and pro-angiogenic signalling in endothelial cells. Biochem Soc Trans 37: 1179-1183.

THOMPSON, IR, CHAND, AN, JONAS, KC; BURRIN, JM, STEINHELPER, ME, WHEELER-JONES, CP, MCARDLE, CA, FOWKES, RC. (2009).
Molecular characterisation and functional interrogation of a local natriuretic peptide system in rodent pituitaries, alpha T3-1 and L beta T2 gonadotroph cells. J Endocrinol : 203 (2): 215-229.

DE PASCALE C, GRAHAM V, FOWKES RC, WHEELER-JONES CPD*, BOTHAM KM* (2009).
Suppression of nuclear factor-B activity in macrophages by chylomicron remnants: modulation by the fatty acid composition of the particles. FEBS J. 276, 5689-5702, *equal contribution 

MACEY MG, WOLF SI, WHEELER-JONES CPD AND LAWSON C (2009).
Expression of blood coagulation factors on monocytes after exposure to TNF-treated endothelium in a novel whole blood model of arterial flow. Immunol Meth 350, 133-41.

SHAWCROSS DL, WRIGHT GA, STADLBAUER V, HODGES SJ, DAVIES NA, WHEELER-JONES CPD, PITSILLIDES AA, JALAN R. (2008).
Ammonia impairs neutrophil phagocytic function in liver disease. Hepatology 48(4):1202-12.

CLARKIN CE, GARONNA E, PITSILLIDES AA AND WHEELER-JONES CPD. (2008). Heterotypic contact reveals a COX-2-mediated suppression of osteoblast differentiation by endothelial cells: A negative modulatory role for prostanoids in VEGF-mediated cell: cell communication? Exp Cell Res. 314: 3152-3161.

WHEELER-JONES, C. P. (2008)
Regulation of endothelial prostacyclin synthesis by Protease-activated receptors: mechanisms and significance. Pharmacol Rep 60, 109-118.

CLARKIN, C. E., EMERY, R. J., PITSILLIDES, A. A. & WHEELER-JONES, C. P. (2008) Evaluation of VEGF-mediated signaling in primary human cells reveals a paracrine action for VEGF in osteoblast-mediated crosstalk to endothelial cells. J Cell Physiol 214, 537-544.

RITCHIE, E., SAKA, M., MACKENZIE, C., DRUMMOND, R., WHEELER-JONES, C., KANKE, T. & PLEVIN, R. (2007)
Cytokine upregulation of proteinase-activated-receptors 2 and 4 expression mediated by p38 MAP kinase and inhibitory kappa B kinase beta in human endothelial cells. Br J Pharmacol 150, 1044-1054.

WHEELER-JONES CPD (2007).
Chylomicron remnants: mediators of endothelial dysfunction? Biochem Soc Trans 35:442-5. 

NAPOLITANO, M., DE PASCALE, C., WHEELER-JONES, C., BOTHAM, K. M. & BRAVO, E. (2007)
Effects of lycopene on the induction of foam cell formation by modified LDL. Am J Physiol Endocrinol Metab 293, E1820-1827.

SYEDA, F., GROSJEAN, J., HOULISTON, R. A., KEOGH, R. J., CARTER, T. D., PALEOLOG, E. & WHEELER-JONES, C. P. (2006)
Cyclooxygenase-2 induction and prostacyclin release by protease-activated receptors in endothelial cells require cooperation between mitogen-activated protein kinase and NF-kappaB pathways. J Biol Chem 281, 11792-11804.

LEWTHWAITE, J. C., BASTOW, E. R., LAMB, K. J., BLENIS, J., WHEELER-JONES, C. P. & PITSILLIDES, A. A. (2006)
A specific mechanomodulatory role for p38 MAPK in embryonic joint articular surface cell MEK-ERK pathway regulation. J Biol Chem 281, 11011-11018.

DE PASCALE, C., AVELLA, M., PERONA, J. S., RUIZ-GUTIERREZ, V., WHEELER-JONES, C. P. & BOTHAM, K. M. (2006)
Fatty acid composition of chylomicron remnant-like particles influences their uptake and induction of lipid accumulation in macrophages. FEBS J 273, 5632-5640.

MAGUIRE, M., POOLE, S., COATES, A. R., TORMAY, P., WHEELER-JONES, C. & HENDERSON, B. (2005)
Comparative cell signalling activity of ultrapure recombinant chaperonin 60 proteins from prokaryotes and eukaryotes. Immunology 115, 231-238.

BOTHAM KM, BRAVO E, ELLIOTT J AND WHEELER-JONES CPD (2005).
Direct interaction of dietary lipids carried in chylomicron remnants with cells of the artery wall: implications for atherosclerosis development. Curr. Pharmaceut Design 11, 3681-3695. 

BASTOW, E. R., LAMB, K. J., LEWTHWAITE, J. C., OSBORNE, A. C., KAVANAGH, E., WHEELER-JONES, C. P. & PITSILLIDES, A. A. (2005)
Selective activation of the MEK-ERK pathway is regulated by mechanical stimuli in forming joints and promotes pericellular matrix formation. J Biol Chem 280, 11749-11758.

HODGES, R. J., JENKINS, R. G., WHEELER-JONES, C. P., COPEMAN, D. M., BOTTOMS, S. E., BELLINGAN, G. J., NANTHAKUMAR, C. B., LAURENT, G. J., HART, S. L., FOSTER, M. L. & MCANULTY, R. J. (2004)
Severity of lung injury in cyclooxygenase-2-deficient mice is dependent on reduced prostaglandin E(2) production. Am J Pathol 165, 1663-1676.

ZUPANCIC, G., OGDEN, D., MAGNUS, C. J., WHEELER-JONES, C. & CARTER, T. D. (2002)
Differential exocytosis from human endothelial cells evoked by high intracellular Ca(2+) concentration. J Physiol 544, 741-755.

WYATT, A. W., STEINERT, J. R., WHEELER-JONES, C. P., MORGAN, A. J., SUGDEN, D., PEARSON, J. D., SOBREVIA, L. & MANN, G. E. (2002)
Early activation of the p42/p44MAPK pathway mediates adenosine-induced nitric oxide production in human endothelial cells: a novel calcium-insensitive mechanism. FASEB J 16, 1584-1594.

KEOGH, R. J., HOULISTON, R. A. & WHEELER-JONES, C. P. (2002)
Thrombin-stimulated Pyk2 phosphorylation in human endothelium is dependent on intracellular calcium and independent of protein kinase C and Src kinases. Biochem Biophys Res Commun 294, 1001-1008.

KEOGH, R. J., HOULISTON, R. A. & WHEELER-JONES, C. P. (2002)
Human endothelial Pyk2 is expressed in two isoforms and associates with paxillin and p130Cas. Biochem Biophys Res Commun 290, 1470-1477.

HOULISTON, R. A., KEOGH, R. J., SUGDEN, D., DUDHIA, J., CARTER, T. D. & WHEELER-JONES, C. P. (2002)
Protease-activated receptors upregulate cyclooxygenase-2 expression in human endothelial cells. Thromb Haemost 88, 321-328.

GLIKI, G., WHEELER-JONES, C. & ZACHARY, I. (2002)
Vascular endothelial growth factor induces protein kinase C (PKC)-dependent Akt/PKB activation and phosphatidylinositol 3'-kinase-mediates PKC delta phosphorylation: role of PKC in angiogenesis. Cell Biol Int 26, 751-759.

DEWI, D. A., ABAYASEKARA, D. R. & WHEELER-JONES, C. P. (2002)
Requirement for ERK1/2 activation in the regulation of progesterone production in human granulosa-lutein cells is stimulus specific. Endocrinology 143, 877-888.

JESSOP, H. L., SJOBERG, M., CHENG, M. Z., ZAMAN, G., WHEELER-JONES, C. P. & LANYON, L. E. (2001)
Mechanical strain and estrogen activate estrogen receptor alpha in bone cells. J Bone Miner Res 16, 1045-1055.

HOULISTON, R. A. & WHEELER-JONES, C. P. (2001)
sPLA(2) cooperates with cPLA(2)alpha to regulate prostacyclin synthesis in human endothelial cells. Biochem Biophys Res Commun 287, 881-887.

HOULISTON, R. A., PEARSON, J. D. & WHEELER-JONES, C. P. (2001)
Agonist-specific cross talk between ERKs and p38(mapk) regulates PGI(2) synthesis in endothelium. Am J Physiol Cell Physiol 281, C1266-1276.

GLIKI, G., ABU-GHAZALEH, R., JEZEQUEL, S., WHEELER-JONES, C. & ZACHARY, I. (2001)
Vascular endothelial growth factor-induced prostacyclin production is mediated by a protein kinase C (PKC)-dependent activation of extracellular signal-regulated protein kinases 1 and 2 involving PKC-delta and by mobilization of intracellular Ca2+. Biochem J 353, 503-512.

Caroline teaches cardiovascular anatomy, physiology and pharmacology to BSc Bioveterinary Science students, to first and second year BVetMed students and to students on the accelerated Graduate BVetMed course.She was the BVetMed Cardiovascular and Respiratory Strand Leader prior to her appointment as Head of Comparative Biomedical Sciences.

Caroline has been actively involved in curriculum development and in teaching and assessment of the BVetMed and BSc programmes throughout her academic career at the RVC. She established and co-ordinated the 3rd year programme for the BSc BioVet Sci degree, organised the alliance with King’s College London, was BSc Course Director for 2 years, and  Director of Intercalation and Chairman of the BSc Committee for 6 years. She has been involved in administration of teaching activity throughout her career, sitting on/chairing numerous undergraduate and postgraduate committees, including examination boards for the BVetMed and BSc programmes and the Course Management Committee for the MSc in Veterinary Education.   

Caroline has been external examiner for pre-clinical veterinary medicine programmes at Nottingham, Bristol and Dublin and external examiner for biomedical sciences undergraduate and Masters level degrees at several other universities,  including Imperial and Kings College London. She is a Fellow of the Higher Education Academy.

Caroline is an advocate of public engagement and widening participation and in recent years has given public lectures on her research and run practical educational events for school children (years 4, 5, 9 and 10) focused on the cardiovascular system.