Armesilla, Angel - University of Wolverhampton - Faculty of Science & Engineering

个人简介

Angel qualified as a molecular biologist (BSc, MSc) in 1990 from the Universidad Complutense de Madrid, Spain, before moving to the Life Science Division, King’s College London to undertake post-graduate research studies. In 1995 Angel obtained his PhD from the Molecular Biology Department, Universidad Autonoma de Madrid, Spain, and began post-doctoral studies into the molecular mechanisms involved in the regulation of signal transduction pathways. In 1998 he began a second postdoctoral study at the Cancer Research UK laboratories, London, and Paterson Institute for Cancer Research, Manchester, where he focused on the implications of transcription factors in cancer progression. Angel took a lectureship in 2001 at the University of Manchester where he investigated the molecular basis of cardiac hypertrophy and heart failure. In 2005 Angel joined the University of Wolverhampton as Reader in Molecular Pharmacology. He lectures on molecular pharmacology and leads a research team investigating the molecular mechanisms implicated in cardiovascular disease.

研究领域

Characterisation of the molecular mechanisms that regulate angiogenesis in the heart after myocardial infarction Ischemic heart disease is the leading cause of morbidity and mortality in the Western world. Cardiac ischemia activates vascular regrowth responses in the heart to protect the myocardial tissue against the ischemic condition by sprouting existing capillaries (angiogenesis) and by developing collateral vessels (arteriogenesis) that bypass the area of stenosis or occlusion. Unfortunately, patients with similar degrees of coronary stenosis show a marked variability in the development of new capillary and collateral arterial vessels, and reperfusion of the ischemic heart is not efficient in many cases. Moreover, formation of new blood vessels is significantly impaired in patients with type 2 diabetes, metabolic syndrome, and severe atherosclerosis. We are studying the molecular mechanisms that regulate reparative angiogenesis and collateral development in the ischemic heart to use this information for the design of efficient therapeutic interventions that promote myocardial revascularization in patients with occluded arteries. Role of the Plasma Membrane Calcium ATPase proteins as regulators of abnormal blood vessel formation in cardiovascular disease The Plasma Membrane Calcium ATPase proteins (PMCAs) are enzymatic low-capacity high-affinity systems involved in the extrusion of Ca2+ from the cell. In humans there are four different PMCA isoforms, PMCA1–4, that are encoded by four independent genes. Studies in recent years have uncovered an increasingly important role for PMCAs as regulators of signal transduction pathways via interaction with specific partner proteins. We have recently reported a novel role for PMCA4 as a negative regulator of VEGF-dependent angiogenesis via interaction with the signalling phosphatase calcineurin. It is well established that VEGF-dependent activation of the calcineurin/NFAT pathway plays a critical role in the progression of pathological angiogenesis. We believe that targeted modulation of PMCA4 functionality might be used to design new therapeutic interventions to promote or attenuate angiogenesis in patients experiencing angiogenic disorders.

近期论文

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Oller J, Alfranca A, Méndez-Barbero N, Villahoz S, Lozano-Vidal N, Martín-Alonso M, Arroyo AG, Escolano A, Armesilla AL, Campanero MR, Redondo JM. C/EBPβ and Nuclear Factor of Activated T Cells Differentially Regulate Adamts-1 Induction by Stimuli Associated with Vascular Remodelling. Mol Cell Biol (2015) 35(19):3409-22. Liu P, Wang Z, Brown S, Kannappan V, Tawari PE, Jiang W, Irache JM, Tang JZ, Armesilla AL, Darling JL, Tang X, Wang W. Liposome encapsulated Disulfiram inhibits NFκB pathway and targets breast cancer stem cells in vitro and in vivo. Oncotarget (2014) 5(17):7471-85. Baggott RR, Alfranca A, López-Maderuelo D, Mohamed TM, Escolano A, Oller J, Ornes BC, Kurusamy S, Rowther FB, Brown JE, Oceandy D, Cartwright EJ, Wang W, Gómez-del Arco P, Martínez-Martínez S, Neyses L, Redondo JM, Armesilla AL. Plasma membrane calcium ATPase isoform 4 inhibits vascular endothelial growth factor-mediated angiogenesis through interaction with calcineurin. Arterioscler Thromb Vasc Biol (2014) 34(10):2310-20. Liu P, Kumar IS, Brown S, Kannappan V, Tawari PE, Tang JZ, Jiang W, Armesilla AL, Darling JL, Wang W. Disulfiram targets cancer stem-like cells and reverses resistance and cross-resistance in acquired paclitaxel-resistant triple-negative breast cancer cells. Br J Cancer (2013) 109(7):1876-85. Amoah V, Storey RF, Worrall AP, Goodridge K, Lovatt T, Smallwood A, Armesilla AL, Nevill AM, Cotton JM. Near patient anti-platelet response testing over time and gene analysis in patients admitted with acute coronary syndromes. Platelets (2013) 24(8):643-8. Liu P, Brown S, Goktug T, Channathodiyil P, Kannappan V, Hugnot JP, Guichet PO, Bian X, Armesilla AL, Darling JL, Wang W. Cytotoxic effect of disulfiram/copper on human glioblastoma cell lines and ALDH-positive cancer-stem-like cells. Br J Cancer (2012) 107(9):1488-97. Baggott RR, Mohamed TM, Oceandy D, Holton M, Blanc MC, Roux-Soro SC, Brown S, Brown JE, Cartwright EJ, Wang W, Neyses L, Armesilla AL. Disruption of the interaction between PMCA2 and calcineurin triggers apoptosis and enhances paclitaxel-induced cytotoxicity in breast cancer cells. Carcinogenesis (2012) 33(12):2362-8. Amoah V, Smallwood A, Worrall AP, Lovatt T, Armesilla AL, Nevill AM, Cotton JM. Poor aspirin response in diabetic patients presenting with acute coronary syndromes: results using a near patient test. Thromb Res (2011) 128(2):196-9. Yip NC, Fombon IS, Liu P, Brown S, Kannappan V, Armesilla AL, Xu B, Cassidy J, Darling JL, Wang W. Disulfiram modulated ROS-MAPK and NFκB pathways and targeted breast cancer cells with cancer stem cell-like properties. Br J Cancer (2011) 104(10):1564-74. Holton ML, Wang W, Emerson M, Neyses L, Armesilla AL. Plasma membrane calcium ATPase proteins as novel regulators of signal transduction pathways. World J Biol Chem (2010) 1(6):201-8.