Silvia Amadesi
-
+44 (0) 118 378 8098
-
Associate Professor
Module convenor for PM2C2, Part 2 Academic Year Tutor
Research projects
Current Research:
- Protease activated receptors signalling in neurons, glial and endothelial cells
- Molecular mechanisms that control neuronal and non-neuronal cells damage and survival
- Stem cells and neurodegeneration
Background
Numerous serine proteinases including trypsin and neutrophil elastase are released during pathological and inflammatory conditions (e.g., cancer, arthritis, asthma and neurodegenerative diseases) or after tissue injury and ischemia (e.g., myocardial infarction, stroke and intestinal ischemia). By acting on different cell types, proteinases activate cell-surface receptor to activate intracellular signaling cascades that promote and control numerous cellular functions. Dysregulation of these signaling mechanisms may result in excessive neuronal excitation, neurotoxicity, perception of pain, neurogenic inflammation, neurodegeneration and reparative neovascularisation.
My research aim is to elucidate the molecular mechanisms regulating serine proteinase -induced cellular responses. In particular, my research aims to clarify how proteinases, by cross talking with ion channels such as TRPV1 and TRPV4, affect the functions of neuronal, glial and endothelial cells. Understanding the molecular mechanisms underlying serine proteinase -mediated processes will help to identify new molecular targets for potential therapeutic intervention.
This might aid the development of new drugs aimed at preventing the advancement of pathological conditions that lead to illness including Alzheimer's and Parkinson's diseases or at treating inflammations and rescue damaged organs.
Publications
- Poole, D. , Amadesi, S. , Veldhuis, N. , Abogadie, F. , Lieu, T. , Darby, W. , Liedtke, W. , Lew, M. , McIntyre, P. , Bunnett, N. (2013) Protease-activated receptor 2 (PAR2) protein and transient receptor potential vanilloid 4 (TRPV4) protein coupling is required for sustained inflammatory signaling. The Journal of Biological Chemistry , 288 (8). pp. 5790-5802. ISSN: 1083-351X | doi: https://dx.doi.org/10.1074/jbc.M112.438184
- Amadesi, S. , Reni, C. , Katare, R. , Meloni, M. , Oikawa, A. , Beltrami, A. , Avolio, E. , Cesselli, D. , Fortunato, O. , Spinetti, G. , Ascione, R. , Cangiano, E. , Valgimigli, M. , Hunt, S. , Emanueli, C. , Madeddu, P. (2012) Role for substance p-based nociceptive signaling in progenitor cell activation and angiogenesis during ischemia in mice and in human subjects. Circulation , 125 (14). pp. 1774-1786. ISSN: 1524-4539 | doi: https://dx.doi.org/10.1161/CIRCULATIONAHA.111.089763
- Kränkel, N. , Spinetti, G. , Amadesi, S. , Madeddu, P. (2011) Targeting stem cell niches and trafficking for cardiovascular therapy.. Pharmacology & Therapeutics , 129 (1). pp. 62-81. ISSN: 0163-7258 | doi: https://dx.doi.org/10.1016/j.pharmthera.2010.10.002
- Ceppa, E. , Cattaruzza, F. , Lyo, V. , Amadesi, S. , Pelayo, J. , Poole, D. , Vaksman, N. , Liedtke, W. , Cohen, D. , Grady, E. , Bunnett, N. , Kirkwood, K. (2010) Transient receptor potential ion channels V4 and A1 contribute to pancreatitis pain in mice.. American Journal of Physiology Gastrointestinal and Liver Physiology , 299 (3). pp. G556-G571. ISSN: 0193-1857 | doi: https://dx.doi.org/10.1152/ajpgi.00433.2009
- Amadesi, S. , Grant, A. , Cottrell, G. , Vaksmam, N. , Poole, D. , Rozengurt, E. , Bunnett, N. (2009) Protein kinase D isoforms are expressed in rat and mouse primary sensory neurons and are activated by agonists of protease-activated receptor 2. Journal of Comparative Neurology , 516 (2). pp. 141-156. ISSN: 1096-9861 | doi: https://dx.doi.org/10.1002/cne.22104
- Cottrell, G. , Padilla, B. , Amadesi, S. , Poole, D. , Murphy, J. , Hardt, M. , Roosterman, D. , Steinhoff, M. , Bunnett, N. (2009) Endosomal endothelin-converting enzyme-1: a regulator of beta-arrestin-dependent ERK signaling. Journal of Biological Chemistry , 284 (33). pp. 22411-22425. ISSN: 1083-351X | doi: https://dx.doi.org/10.1074/jbc.M109.026674
- Andrè, E. , Campi, B. , Materazzi, S. , Trevisani, M. , Amadesi, S. , Massi, D. , Creminon, C. , Vaksman, N. , Nassini, R. , Civelli, M. , Baraldi, P. , Poole, D. , Bunnett, N. , Geppetti, P. , Patacchini, R. (2008) Cigarette smoke-induced neurogenic inflammation is mediated by α,β-unsaturated aldehydes and the TRPA1 receptor in rodents. The Journal of Clinical Investigation , 118 (7). pp. 2574-2582. ISSN: 0021-9738 | doi: https://dx.doi.org/10.1172/JCI34886
- Materazzi, S. , Nassini, R. , Andrè, E. , Campi, B. , Amadesi, S. , Trevisani, M. , Bunnett, N. , Patacchini, R. , Geppetti, P. (2008) Cox-dependent fatty acid metabolites cause pain through activation of the irritant receptor TRPA1.. Proceedings of the National Academy of Sciences of the United States of America , 105 (33). pp. 12045-12050. ISSN: 0027-8424 | doi: https://dx.doi.org/10.1073/pnas.0802354105
- Kayssi, A. , Amadesi, S. , Bautista, F. , Bunnett, N. , Vanner, S. (2007) Mechanisms of protease-activated receptor 2-evoked hyperexcitability of nociceptive neurons innervating the mouse colon. Journal of Physiology , 580 (3). pp. 977-991. ISSN: 0022-3751 | doi: https://dx.doi.org/10.1113/jphysiol.2006.126599
- Cottrell, G. , Amadesi, S. , Pikios, S. , Camerer, E. , Willardsen, J. , Murphy, B. , Caughey, G. , Wolters, P. , Coughlin, S. , Peterson, A. , Knecht, W. , Pothoulakis, C. , Bunnett, N. , Grady, E. (2007) Protease-activated receptor 2, dipeptidyl peptidase I, and proteases mediate Clostridium difficile toxin A enteritis. Gastroenterology , 132 (7). pp. 2422-2437. ISSN: 0016-5085 | doi: https://dx.doi.org/10.1053/j.gastro.2007.03.101
- Grant, A. , Cottrell, G. , Amadesi, S. , Trevisani, M. , Nicoletti, P. , Materazzi, S. , Altier, C. , Cenac, N. , Zamponi, G. , Bautista-Cruz, F. , Lopez, C. , Joseph, E. , Levine, J. , Liedtke, W. , Vanner, S. , Vergnolle, N. , Geppetti, P. , Bunnett, N. (2007) Protease-activated receptor 2 sensitizes the transient receptor potential vanilloid 4 ion channel to cause mechanical hyperalgesia in mice. Journal of Physiology , 578 (3). pp. 715-733. ISSN: 0022-3751 | doi: https://dx.doi.org/10.1113/jphysiol.2006.121111
- Knecht, W. , Cottrell, G. , Amadesi, S. , Mohlin, J. , Skaregarde, A. , Gedda, K. , Peterson, A. , Chapman, K. , Hollenberg, M. , Vergnolle, N. , Bunnett, N. (2007) Trypsin IV or mesotrypsin and p23 cleave protease-activated receptors 1 and 2 to induce inflammation and hyperalgesia. The Journal of Biological Chemistry , 282 (36). pp. 26089-26100. ISSN: 1083-351X | doi: https://dx.doi.org/10.1074/jbc.M703840200
- Grant, A. , Amadesi, S. , Bunnett, N. (2006) Protease-activated receptors: mechanisms by which proteases sensitize TRPV channels to induce neurogenic inflammation and pain. In: Heller, S. and Liedtke, W. , (eds.) TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades. CRC Press pp. 422-434. ISBN: 9781420005844 | doi: https://dx.doi.org/10.1201/9781420005844.ch31 (Chapter 8)
- Amadesi, S. , Cottrell, G. , Divino, L. , Chapman, K. , Grady, E. , Bautista, F. , Karanjia, R. , Barajas-Lopez, C. , Vanner, S. , Vergnolle, N. , Bunnett, N. (2006) Protease-activated receptor 2 sensitizes TRPV1 by protein kinase Cepsilon- and A-dependent mechanisms in rats and mice. Journal of Physiology , 575 (2). pp. 555-571. ISSN: 0022-3751 | doi: https://dx.doi.org/10.1113/jphysiol.2006.111534
- Jacob, C. , Yang, P. , Darmoul, D. , Amadesi, S. , Saito, T. , Cottrell, G. , Coelho, A. , Singh, P. , Grady, E. , Perdue, M. , Bunnett, N. (2005) Mast cell tryptase controls paracellular permeability of the intestine: role of protease-activated receptor 2 and beta-arrestins. Journal of Biological Chemistry , 280 (31). pp. 936-948. ISSN: 1083-351X | doi: https://dx.doi.org/10.1074/jbc.M506338200
- Amadesi, S. and Bunnett, N. (2004) Protease-activated receptors: protease signaling in the gastrointestinal tract. Current Opinion in Pharmacology , 4 (6). pp. 551-556. ISSN: 1471-4892 | doi: https://dx.doi.org/10.1016/j.coph.2004.08.004
- Amadesi, S. , Nie, J. , Vergnolle, N. , Cottrell, G. , Grady, E. , Trevisani, M. , Manni, C. , Geppetti, P. , McRoberts, J. , Ennes, H. , Davis, J. , Mayer, E. , Bunnett, N. (2004) Protease-activated receptor 2 sensitizes the capsaicin receptor transient receptor potential vanilloid receptor 1 to induce hyperalgesia. The Journal of Neuroscience , 24 (18). pp. 4300-4312. ISSN: 1529-2401 | doi: https://dx.doi.org/10.1523/JNEUROSCI.5679-03.2004
- Cottrell, G. , Amadesi, S. , Grady, E. , Bunnett, N. (2004) Trypsin IV, a novel agonist of protease-activated receptors 2 and 4. Journal of Biological Chemistry , 279 (14). pp. 13532-13539. ISSN: 1083-351X | doi: https://dx.doi.org/10.1074/jbc.M312090200
- Rigoni, M. , Trevisani, M. , Gazzieri, D. , Nadaletto, R. , Tognetto, M. , Creminon, C. , Davis, J. , Campi, B. , Amadesi, S. , Geppetti, P. , Harrison, S. (2003) Neurogenic responses mediated by vanilloid receptor-1 (TRPV1) are blocked by the high affinity antagonist, iodo-resiniferatoxin. British Journal of Pharmacology , 138 (5). pp. 977-985. ISSN: 0007-1188
- Cottrell, G. , Amadesi, S. , Schmidlin, F. , Bunnett, N. (2003) Protease-activated receptor 2: activation, signalling and function. Biochemical Society Transactions , 31 (6). pp. 1191-1197. ISSN: 1470-8752
- Trevisani, M. , Smart, D. , Gunthorpe, M. , Tognetto, M. , Barbieri, M. , Campi, B. , Amadesi, S. , Gray, J. , Jerman, J. , Brough, S. , Owen, D. , Smith, G. , Randall, A. , Harrison, S. , Bianchi, A. , Davis, J. , Geppetti, P. (2002) Ethanol elicits and potentiates nociceptor responses via the vanilloid receptor-1. Nature Neuroscience , 5 (6). pp. 546-551. ISSN: 1546-1726 | doi: https://dx.doi.org/10.1038/nn0602-852
- Schmidlin, F. , Amadesi, S. , Dabbagh, K. , Lewis, D. , Knott, P. , Bunnett, N. , Gater, P. , Geppetti, P. , Bertrand, C. , Stevens, M. (2002) Protease-activated receptor 2 mediates eosinophil infiltration and hyperreactivity in allergic inflammation of the airway. The Journal of Immunology , 169 (9). pp. 5315-5321. ISSN: 0022-1767 | doi: https://dx.doi.org/10.4049/jimmunol.169.9.5315
- Amadesi, S. , Moreau, J. , Tognetto, M. , Springer, J. , Trevisani, M. , Naline, E. , Advenier, C. , Fisher, A. , Vinci, D. , Mapp, C. , Miotto, D. , Cavallesco, G. , Geppetti, P. (2001) NK1 receptor stimulation causes contraction and inositol phosphate increase in medium-size human isolated bronchi. American Journal of Respiratory and Critical Care Medicine , 163 (5). pp. 1206-1211. ISSN: 1535-4970 | doi: https://dx.doi.org/10.1164/ajrccm.163.5.2002079
- Schmidlin, F. , Amadesi, S. , Vidil, R. , Trevisani, M. , Martinet, N. , Caughey, G. , Tognetto, M. , Cavallesco, G. , Mapp, C. , Geppetti, P. , Bunnett, N. (2001) Expression and function of proteinase-activated receptor 2 in human bronchial smooth muscle. American Journal of Respiratory and Critical Care Medicine , 164 (7). pp. 1276-1281. ISSN: 1535-4970 | doi: https://dx.doi.org/10.1164/ajrccm.164.7.2101157
- Ricciardolo, F. , Steinhoff, M. , Amadesi, S. , Guerrini, R. , Tognetto, M. , Trevisani, M. , Creminon, C. , Bertrand, C. , Bunnett, N. , Fabbri, L. , Salvadori, S. , Geppetti, P. (2000) Presence and bronchomotor activity of protease-activated receptor-2 in guinea pig airways. American Journal of Respiratory and Critical Care Medicine , 161 (5). pp. 1672-1680. ISSN: 1535-4970 | doi: https://dx.doi.org/10.1164/ajrccm.161.5.9907133
- Steinhoff, M. , Vergnolle, N. , Young, S. , Tognetto, M. , Amadesi, S. , Ennes, H. , Trevisani, M. , Hollenberg, M. , Wallace, J. , Caughey, G. , Mitchell, S. , Williams, L. , Geppetti, P. , Mayer, E. , Bunnett, N. (2000) Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism. Nature medicine , 6 (2). pp. 151-158. ISSN: 1078-8956 | doi: https://dx.doi.org/10.1038/72247