Cardiovascular

Cells looked at through a microscope

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.

We offer a Biomedical Science PhD, and a range of innovative research project opportunities for postgraduate researchers.

For more information, email Dr Joe Bird at joseph.bird@aru.ac.uk

Members

Academic staff

Dr Joseph Bird - Head of the Cardiovascular Research Group

Dr Joseph Bird 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.

Dr Nicholas Pugh

Dr Nicholas Pugh 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.

Dr Havovi Chichger

Dr Havovi Chichger 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.

Dr Grisha Pirianov

Dr Grisha Pirianov 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.

Dr Clett Erridge

Dr Clett Erridge 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.

Dr Linda King

Dr Linda King 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.

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Post-doctoral research students

Dr Niaz Ahmed

Niaz is a postdoctoral research associate working with Dr Nick Pugh. Niaz studied for his PhD with Nick before becoming a PDRA in the group. He has research interests focussing on the role of zinc as a secondary messenger during platelet activation.

PhD researchers - current

Klaudia Rodi

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 Umerah

Kenechukwu is a first year PhD student supervised by Dr Clett Erridge. She is researching the regulation of lipid metabolism in macrophages.

Elizabeth Seetharaman

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 mineralization.

Charys Palmer

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.

PhD researchers - alumni

Dr Aparna Shil

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.

Dr Emmanuella Enuwosa

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.

Dr Niaz Ahmed

Niaz completed his PhD in 2019, supervised by Dr Nick Pugh, Dr Havovi Chichger and Dr Linda King. Niaz studied the role of zinc as a secondary messenger during platelet activation.

Activities, partnerships and projects

Research funding

2018-2021: British Heart Foundation project grant. Investigation of the mechanisms and significance of secondary zinc messaging platelets (Dr Nick Pugh)

Conferences

  • 2019 Platelet UK meeting, Cambridge, UK. Organising Committee. (Dr Nick Pugh).
  • 2019 (August), Gordon Research Conference – Angiogenesis, Rhode Island. An orphan GPRC which regulates neovascularisation – a novel target for anti-VEGF therapies? Presentation (Dr Havovi Chichger).
  • 2018 Zinc UK meeting, ARU, UK. Organising Committee. (Dr Nick Pugh).
  • 2018 (June), International Vascular Biology Organisation conference, Helsinki. Bitter taste receptors regulate microvascular permeability. Presentation. (Dr Havovi Chichger).
  • 2018 (June), NHLBI Research Seminar, Imperial College London. The Role of Taste Sensing in the Pulmonary Endothelium. Presentation. (Dr Havovi Chichger).
  • 2018 (March), Diabetes UK Professional Conference, London. Activation of the sweet taste receptor attenuates VEGF-induced angiogenesis. Presentation (Dr Havovi Chichger).
  • 2017 (December), ‘Future Physiology’ meeting, Physiological Society, Leeds, UK. Acetylcholine and Adrenaline increase outward potassium currents in chondrocytes from articular cartilage. Presentation (Dr Joe Bird).
  • 2015 (June), CLINAM, Basel, Switzerland. Nano-technology Lipodisq delivery of novel mimetic TLR4 antagonist IAXO-102 modulates in vitro and in vivo non-hematopoietic TLR4 signalling. Presentation (Dr Grisha Pirianov).
  • 2015 (March). 83rd European Atherosclerosis Society Congress, Glasgow, Scotland. Novel mimetic TLR4 antagonist IAXO-102 prevents experimental aortic aneurysm development. Presentation (Dr Grisha Pirianov).
  • 2015 (March). 83rd European Atherosclerosis Society Congress, Glasgow, Scotland. Identifying active vascular micro‐calcification by 18F‐sodium fluoride positron emission tomography. Presentation (Dr Joe Bird).
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Patents acquired

Inventor for UK and USA patent – EP2019/056677 (Dr Havovi Chichger).

Collaborations

Key publications

2020

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.

Read more about 2020.

2019

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

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2018

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

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2017

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.

2016

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

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2015

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

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2014

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

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