The Cardiovascular Research Group has a wide range of cardiovascular research interests covering many aspects of health and disease. Our current specialisms include diabetes, platelet biology and thrombosis, inflammation, drug discovery, and metabolism.
We're part of the wider Biomedical Research Group.
Joe has a primary research interest in the development of vascular lesions and in particular, ectopic mineralisation and inflammatory processes. He is concerned with both the physiological processes involved and the signalling pathways which direct them. His wider interests are in skeletal tissue pathologies and the impact of ageing processes such as replicative senescence on the development of these vascular and skeletal lesions.
Nick focuses his research interests on the signalling mechanisms used by platelets during pathophysiological thrombus formation. He is particularly interested in the role of ion channels and transporters in platelet function and studying platelet behaviour in models of thrombus formation in flowing blood. He also has an interest in lipotoxicity and in the development of novel reagents to study platelet function.
Havovi researches cellular mechanisms which regulate the endothelium in human disease and the impact of diabetes on renal and small intestinal glucose transport across the epithelium. This includes both transport processes and intracellular signalling pathways. Additionally, she has an interest in the gut microbiota and gastric permeability.
Grisha is focused on translational medicine, which includes discovering novel drugs and therapeutic targets for pharmacological intervention of inflammatory based diseases including cancer immunotherapy. His primary research area is on the innate immune system and the mechanisms by which pattern recognition receptors within this system are regulated in vascular inflammatory pathologies such as atherosclerosis. He has additional interests in the anti-inflammatory and anti-cancer properties of natural plant extracts.
Clett focuses his research on the mechanisms connecting inflammation to lipid metabolism, particularly in the context of foam cell formation in macrophages and coronary artery disease. His interests encompass the impact that the food and gut microbiota can have on inflammatory signalling in health and disease, and novel approaches to the engineering of immune responses in the context of immunotherapies for various conditions, including atherosclerosis.
Linda is focused on the metabolic changes associated with ischaemic heart disease and diabetes. In particular, she is interested in the impact of lipotoxicity on glucose metabolism and the resultant changes in cellular response to insulin signalling. Linda is also concerned with the regulation of G-protein couple receptors and melanocortin 1 receptor signalling.
Klaudia is a first year PhD student supervised by Dr Havovi Chichger. She is researching the molecular mechanisms regulating vascular function in pancreatic cancer.
Kenechukwu is a first year PhD student supervised by Dr Clett Erridge. She is researching the regulation of lipid metabolism in macrophages.
Elizabeth is starting as a PhD student supervised by Dr Joe Bird. She is investigating the role of endocrine disrupting hormones on cell function and mineraliation.
Charys is a final year PhD student supervised by Dr Grisha Pirianov. She is studying novel small molecules Toll like receptor 4 modulators for treatment of inflammatory-based diseases.
Aparna completed her PhD, supervised by Dr Havovi Chichger, in 2020. Her project was based on the impact of food supplements on the intestinal epithelial barrier. Her PhD findings have, to date, been published in Nutrients, the American Journal of Physiology and Pulmonary Circulation.
Emmanuella completed her PhD, supervised by Dr Havovi Chichger, in 2020. Her project focused on the molecular mechanisms regulating VEGF-induced leak of the glomerular endothelium. Her PhD findings have, to date, been published in Graefe’s Archive.
The cardiovascular group members have esteem within their respective areas of research and are active in contributing to publication of research, the raising of research funds from research councils, charities and industry, membership of journal editorial boards and research society committees, and collaboration with other groups.
2018-2021: British Heart Foundation project grant. Investigation of the mechanisms and significance of secondary zinc messaging platelets (Dr Nick Pugh)
Inventor for UK and USA patent – EP2019/056677 (Dr Havovi Chichger).
Harrington, E. O., Braza, J., Shil, A., Chichger, H., 2020. Extracellular vesicles released from p18 overexpressing pulmonary endothelial cells are barrier protective – potential implications for acute respiratory distress syndrome. Pulmonary Circulation, 10(3), p. 1.
Shil, A., Olusanya, O., Ghufoor, Z., Forson, B., Marks, J., Chichger H., 2020. Artificial sweeteners disrupt tight junctions and barrier function in the intestinal epithelium through activation of the sweet taste receptor, T1R3. Nutrients, 12(6), p. 1862.
Pardhan, S., Vaughan, M., Zhang, J., Smith, L., Chichger, H., 2020. Type and frequency of ocular and other known symptoms experienced by people who self diagnosed as suffering from COVID-19 in the UK. medRxiv, June 22.
Keegan, G., Pardhan, S., Chichger, H., 2020. Lutein and zeaxanthin attenuates VEGF-induced neovascularisation in human retinal microvascular endothelial cells through a Nox4-dependent pathway. Experimental Eye Research, 197, 108104.
Ventetuolo, C. E., Aliotta, J. M., Braza, J., Chichger, H., Dooner, M., McGuirl, D., Mullin, C. J., Newton, J., Pereira, M., Princiotto, A., Quesenberry, P. J., Walsh, T., Whittenhall, M., Klinger, J. R., Harrington, E. O., 2020. Culture of pulmonary artery endothelial cells from pulmonary artery catheter balloon tips: considerations for use in pulmonary vascular disease. European Respiratory Journal, 55(3), 1901313.
Ahmed, N. S., Lopes Pires, M. E., Taylor, K. A., Pugh, N., 2019. Agonist-Evoked Increases in Intra-Platelet Zinc Couple to Functional Responses. Thromb Haemost, 119(1), pp. 128-139. doi: 10.1055/s-0038-1676589
Nelson, C.P., Erridge, C., 2019. Are toll-like receptors potential drug targets for atherosclerosis? Evidence from genetic studies to date. Immunogenetics, 71(1), pp. 1-11. doi: 10.1007/s00251-018-1092-0
Faraj, T. A., Stover, C., Erridge, C., 2019. Dietary Toll-Like Receptor Stimulants Promote Hepatic Inflammation and Impair Reverse Cholesterol Transport in Mice via Macrophage-Dependent Interleukin-1 Production. Front Immunol, 20, 10:1404. doi: 10.3389/fimmu.2019.01404
Rodrigues, J. G. C., Chichger, H., 2019. At Physiologically Relevant Concentrations, Valproic Acid and Lithium Carbonate Reduce Oxidative Stress in Human Astrocytoma Cells. European Medical Journal – Neurology, 7(1), p. 71.
Chichger, H., Rounds, S., Harrington, E. O., 2019. Endosomes and Autophagy: Regulators of Pulmonary Endothelial Cell Homeostasis in Health and Disease. Antioxidants & Redox Signalling, 31(13), p. 994.
Rolev, K., Coussons, P., King, L., Rajan M., 2019. Experimental models of corneal endothelial cell therapy and translational challenges to clinical practice. Exp Eye Res, 188, 107794. doi: 10.1016/j.exer.2019.107794
Palmer, C., Peri, F., Neumann, F., Ahmad, F., Leake, D. S., Pirianov, G., 2018. The synthetic glycolipid-based TLR4 antagonist FP7 negatively regulates in vitro and in vivo haematopoietic and non-haematopoietic vascular TLR4 signalling. Innate Immun, 24(7), pp. 411-421. doi: 10.1177/1753425918798904
Herbert, K. E., Erridge, C., 2018. Regulation of low-density lipoprotein cholesterol by intestinal inflammation and the acute phase response. Cardiovasc Res, 114, pp. 226-232.
Facchini, F. A., Zaffaroni, L., Minotti, A., Rapisarda, S., Calabrese, V., Forcella, M., Fusi, P., Airoldi, C., Ciaramelli, C., Billod, J. M., Schromm, A. B., Braun, H., Palmer, C., Beyaert, R., Lapenta, F., Jerala, R., Pirianov, G., Martin-Santamaria, S., Peri, F., 2018. Structure-Activity Relationship in Monosaccharide-Based Toll-Like Receptor 4 (TLR4) Antagonists. J Med Chem, 61(7), pp. 2895-2909. doi: 10.1021/acs.jmedchem.7b01803
Rolev, K., OʼDonovan, D. G., Coussons, P., King, L., Rajan, M. S., 2018. Feasibility Study of Human Corneal Endothelial Cell Transplantation Using an In Vitro Human Corneal Model. Cornea, 37(6), pp. 778-784.
Rosini, S., Bihan, D, Pugh, N., Bonna, A. M., Hulmes, D. H. S, Farndale, R. W., Adams, J. C., 2018. Interactions of Thrombospondin1 with Prolysyl Oxidase and Collagen I Regulate Fibroblast Collagen Matrix via Cell- and Matrix-Loci. Sci Signal, 29, 11(532):eaar2566. doi: 10.1126/scisignal.aar2566
Howes, J. M., Pugh, N., Smethurst, P. A., Hamaia, S., Knauper, V., Visse, R., Malcor, J-D., Farndale, R. W., 2018. MMP-13 binds to platelet receptors αIIbβ3 and GPVI and impairs aggregation and thrombus formation. Res Pract Thromb Haemost, 2(2), pp. 370-379. doi: 10.1002/rth2.12088
Iegre, J. I., Wu, W., Ahmed, N. S., Tan, Y. S., Lopes-Pires, M. E., Gaynord, J. S., Lau, Y. H., Sore, H. F., Verma, C., Pugh, N., Spring, D. R., 2018. Stapled peptides as a new technology to investigate protein-protein interactions in human platelets. Chemical Science, 9, pp. 4638-4643.
Misra. A., Prakash, P., Aggarwal, H., Dhankani, P., Kumar, S., Pandey, C. P., Pugh, N., Bihan D., Barthwal, M. K., Farndale, R. W., Dikshit, D. K., Dikshit, M., 2018. Anti-thrombotic efficacy of S007-867: Pre-clinical evaluation in experimental models of thrombosis in vivo and in vitro. Biochem Pharmacol. 148, pp. 288-297.
Harrington, E. O., Vang, A., Braza, A., Chichger, H., 2018. Activation of the sweet taste receptor, T1R3, by the artificial sweetener sucralose regulates the pulmonary endothelium. American Journal of Physiology – Lung Cellular and Molecular Physiology. 314(1), L165.
Hossain, M. J., Morandi, E., Tanasescu, R., Frakich, N., Caldano, M., Onion, D., Faraj, T. A., Erridge, C., Gran, B., 2018. The Soluble Form of Toll-Like Receptor 2 Is Elevated in Serum of Multiple Sclerosis Patients: A Novel Potential Disease Biomarker. Front Immunol, 9, p. 457.
Taylor, K. A., Ahmed, N., Wilson, D., Harper, M. T. and Pugh, N., 2018. Extracellular chloride is required for efficient activation of secondary signalling pathways during platelet aggregation. Platelets, 29(1), pp. 79-83. doi: 10.1080/09537104.2017.1332367
Faraj, T. A., McLaughlin, C. L., Erridge, C., 2017.Host defences against metabolic endotoxaemia and their impact on lipopolysaccharide detection. Int Rev Immunol, 36, pp. 125-144.
Pugh, N., Maddox, B. D., Bihan, D., Taylor, K. A., Mahaut-Smith, M. P., Farndale, R. W., 2017. Differential integrin activity mediated by platelet collagen receptor engagement under flow conditions. Thromb Haemost, 117(8), pp. 1588-1600.
Herieka, M., Faraj, T. A., Erridge, C., 2016. Reduced dietary intake of pro-inflammatory Toll-like receptor stimulants favourably modifies markers of cardiometabolic risk in healthy men. Nutr Metab Cardiovasc Dis, 26, pp. 194-200.
Taylor, K. A. and Pugh, N., 2016.The contribution of zinc to platelet behaviour during haemostasis and thrombosis. Metallomics, 8(2), pp. 144-55.
Watson, B. R., White, N. A., Taylor, K. A., Howes, J. M., Malcor, J-D., Bihan, D., Sage, S. O., Farndale, R. W., Pugh, N., 2016. Zinc is a transmembrane agonist that induces platelet activation in a tyrosine phosphorylation-dependent manner. Metallomics, 8(1), pp. 91-100.
Ibrahim, B., Sheerin, A. N., Jennert-Burston, K., Bird, J. L. E., Massala, M. V., Illsley, M., James, S. E., Faragher, R. G. A., 2016. Absence of premature senescence in Werner's syndrome keratinocytes. Experimental Gerontology, 83, pp. 139-147. doi: 10.1016/j.exger.2016.07.017
Malkawi, A., Pirianov, G., Torsney, E., Chetter, I., Sakalihasan, N., Loftus, I. M., Nordon, I., Huggins, C., Charolidi, N., Thompson, M., Xu, X. Y., Cockerill, G. W., 2015. Increased Expression of Lamin A/C Correlate with Regions of High Wall Stress in Abdominal Aortic Aneurysms. Aorta (Stamford), 3(5), pp. 152-66. doi: 10.12945/j.aorta.2015.14.069
Howes, J. M., Pugh, N., Knäuper, V., Farndale, R.W., 2015. Modified platelet deposition on matrix metalloproteinase 13 digested collagen I. J Thromb Haemost, 3(12), pp. 2253-9.
Pugh, N., Bihan, D., Perry, D. J. and Farndale, R. W., 2015. Dynamic analysis of platelet deposition to resolve platelet adhesion receptor activity in whole blood at arterial shear rate. Platelets, 26(3), pp. 216-9.
Nelson, C. P., Schunkert, H., Samani, N. J., Erridge, C., 2015. Genetic analysis of leukocyte type-I interferon production and risk of coronary artery disease. Arterioscler Thromb Vasc Biol, 35, pp. 1456-62.
Huggins, C., Peri, F., Neumann, F., Cockerill, G., Pirianov, G. A., 2015. Novel mimetic TLR4 antagonist IAXO-102 inhibits non- haematopoietic TLR4 signalling and prevents aortic aneurysms development. Atherosclerosis, 242(2), pp. 563-70.
Pirianov, G., MacIntyre, D. A., Lee, Y. S., Waddignton, S., Terzidou, V., Mehmet, H., Bennett, P., 2015. Selective inhibition of TLR4/JNK signaling delays experimental preterm labor and prevents neonatal brain damage. Reproduction, 150(4), pp. 266-277.
Charolidi, N., Pirianov, G., Torsney, E., Pearce, S., Laing, K., Nohturfft, A., Cockerill, G. W., 2015. Pioglitazone identifies a new target for aneurysm treatment - role of Egr1 in an experimental murine model of aortic aneurysm. Journal Vascular Surgery, 52(2), pp. 81-93.
Irkle, A., Vesey, A. T., Lewis, D. Y., Skepper, J. N., Bird, J. L. E., Dweck, M. R., Joshi, F. J., Gallagher, F. A., Warburton, E. A., Bennett, M. R., Brindle, K. M., Newby, D. E., Rudd, J. H., Davenport, A. P., 2015. Identifying active vascular micro‐calcification by 18F‐sodium fluoride positron emission tomography. Nature Communications, 6, 7495. doi:10.1038/ncomms8495
de Witt, S. M., Swieringa, F., Cavill, R., Lamers, M. M., van Kruchten, R., Mastenbroek, T., Baaten, C., Coort, S., Pugh, N., Schulz, A., Scharrer, I., Jurk, K., Zieger, B., Clemetson, K. J., Farndale, R. W., Heemskerk, J. W., Cosemans, J. M., 2014. Identification of platelet function defects by multi-parameter assessment of thrombus formation. Nat Commun, 5:4257.
McRobie, H. R., King, L. M., Fanutti, C., Symmons, M. F., Coussons, P. J., 2014. Agouti signalling protein is an inverse agonist to the wildtype and agonist to the melanic variant of the melanocortin- 1 receptor in the grey squirrel (Sciurus carolinensis). FEBS letters, 588, pp. 2335-2343.
McRobie, H. R., King, L. M., Coussons, P., 2014. Agouti signalling protein (ASIP) acts as an inverse agonist to the melanocortin-1 receptor (MC1R) in the wild type grey squirrel (S. carolinensis) and as agonist to the melanic variant (MC1R Delta 24). Journal of Investigative Dermatology, 134(8), pp. 2335-43.
McRobie, H. R., King, L. M., Fanutti, C., Coussons, P. J., Moncrief, N. D., Thomas, A. P. M., 2014. Melanocortin 1 receptor (MC1R) gene sequence variation and melanism in the gray (Sciurus carolinensis), fox (Sciurus niger), and red (Sciurus vulgaris) squirrel. Journal of Heredity, 105 (3), pp. 423-428.
Mouratidis, P., Colston, K., Pirianov, G., 2014. Differential role of apoptosis and autophagy associated with anticancer effect of lupulone (hop β-acid) derivatives on prostate cancer cells. Anticancer Agents Medicinal Chemistry, 14(8), pp. 1169-78.
Cuhlmann, S., Gsell, W., Van der Heiden, K., Habib, J., Tremoleda, J. L., Khalil, M., Turkheimer, F., Meens, M. J., Kwak, B. R., Bird, J. L., Davenport, A. P., Clark, J. C., Haskard, D., Krams, R., Jones, H., Evans, P. C. , 2014. In vivo mapping of vascular inflammation using the translocator protein tracer 18F-FEDAA. Molecular Imaging, 13, pp. 1-11. doi: 10.2310/7290.2014.00014
Herieka, M., Erridge, C., 2014. High-fat meal induced postprandial inflammation. Mol Nutr Food Res, 58(1), pp. 136-46. doi: 10.1002/mnfr.201300104