Staff Profile:Dr Silvia Amadesi
- Name:
- Dr Silvia Amadesi
- Job Title:
- Associate Professor
- Responsibilities:
Module convenor for PM2C2, Part 2 Academic Year Tutor
- Areas of Interest:
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.
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
- Research groups / Centres:
- Publications:
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YNumber of items: 26.
2013
- Poole, D. P., Amadesi, S., Veldhuis, N. A., Abogadie, F. C., Lieu, T., Darby, W., Liedtke, W., Lew, M. J., McIntyre, P. and Bunnett, N. W. (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://doi.org/10.1074/jbc.M112.438184
2012
- Amadesi, S., Reni, C., Katare, R., Meloni, M., Oikawa, A., Beltrami, A. P., Avolio, E., Cesselli, D., Fortunato, O., Spinetti, G., Ascione, R., Cangiano, E., Valgimigli, M., Hunt, S. P., Emanueli, C. and 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://doi.org/10.1161/CIRCULATIONAHA.111.089763
2011
- Kränkel, N., Spinetti, G., Amadesi, S. and Madeddu, P. (2011) Targeting stem cell niches and trafficking for cardiovascular therapy. Pharmacology & Therapeutics, 129 (1). pp. 62-81. ISSN 0163-7258 doi: https://doi.org/10.1016/j.pharmthera.2010.10.002
2010
- Ceppa, E., Cattaruzza, F., Lyo, V., Amadesi, S., Pelayo, J.-C., Poole, D. P., Vaksman, N., Liedtke, W., Cohen, D. M., Grady, E. F., Bunnett, N. W. and Kirkwood, K. S. (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). G556-G571. ISSN 0193-1857 doi: https://doi.org/10.1152/ajpgi.00433.2009
2009
- Amadesi, S., Grant, A. D., Cottrell, G., Vaksmam, N., Poole, D. P., Rozengurt, E. and Bunnett, N. W. (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://doi.org/10.1002/cne.22104
- Cottrell, G., Padilla, B. E., Amadesi, S., Poole, D. P., Murphy, J. E., Hardt, M., Roosterman, D., Steinhoff, M. and Bunnett, N. W. (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://doi.org/10.1074/jbc.M109.026674
2008
- Materazzi, S., Nassini, R., Andrè, E., Campi, B., Amadesi, S., Trevisani, M., Bunnett, N. W., Patacchini, R. and 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://doi.org/10.1073/pnas.0802354105
- Andrè, E., Campi, B., Materazzi, S., Trevisani, M., Amadesi, S., Massi, D., Creminon, C., Vaksman, N., Nassini, R., Civelli, M., Baraldi, P. G., Poole, D. P., Bunnett, N. W., Geppetti, P. and 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://doi.org/10.1172/JCI34886
2007
- Kayssi, A., Amadesi, S., Bautista, F., Bunnett, N. W. and 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://doi.org/10.1113/jphysiol.2006.126599
- Grant, A. D., Cottrell, G. S., Amadesi, S., Trevisani, M., Nicoletti, P., Materazzi, S., Altier, C., Cenac, N., Zamponi, G. W., Bautista-Cruz, F., Lopez, C. B., Joseph, E. K., Levine, J. D., Liedtke, W., Vanner, S., Vergnolle, N., Geppetti, P. and Bunnett, N. W. (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://doi.org/10.1113/jphysiol.2006.121111
- Cottrell, G. S., Amadesi, S., Pikios, S., Camerer, E., Willardsen, J. A., Murphy, B. R., Caughey, G. H., Wolters, P. J., Coughlin, S. R., Peterson, A., Knecht, W., Pothoulakis, C., Bunnett, N. W. and Grady, E. F. (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://doi.org/10.1053/j.gastro.2007.03.101
- Knecht, W., Cottrell, G. S., Amadesi, S., Mohlin, J., Skaregarde, A., Gedda, K., Peterson, A., Chapman, K., Hollenberg, M. D., Vergnolle, N. and Bunnett, N. W. (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://doi.org/10.1074/jbc.M703840200
2006
- Amadesi, S., Cottrell, G. S., Divino, L., Chapman, K., Grady, E. F., Bautista, F., Karanjia, R., Barajas-Lopez, C., Vanner, S., Vergnolle, N. and Bunnett, N. W. (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://doi.org/10.1113/jphysiol.2006.111534
- Grant, A., Amadesi, S. and Bunnett, N. W. (2006) Protease-activated receptors: mechanisms by which proteases sensitize TRPV channels to induce neurogenic inflammation and pain. In: Heller, S. and Liedtke, W. B. (eds.) TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades. CRC Press, pp. 422-434. ISBN 9781420005844 doi: https://doi.org/10.1201/9781420005844.ch31 (Chapter 8)
2005
- Jacob, C., Yang, P.-C., Darmoul, D., Amadesi, S., Saito, T., Cottrell, G. S., Coelho, A.-M., Singh, P., Grady, E. F., Perdue, M. and Bunnett, N. W. (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://doi.org/10.1074/jbc.M506338200
2004
- 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://doi.org/10.1016/j.coph.2004.08.004
- Amadesi, S., Nie, J., Vergnolle, N., Cottrell, G. S., Grady, E. F., Trevisani, M., Manni, C., Geppetti, P., McRoberts, J. A., Ennes, H., Davis, J. B., Mayer, E. A. and Bunnett, N. W. (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://doi.org/10.1523/JNEUROSCI.5679-03.2004
- Cottrell, G. S., Amadesi, S., Grady, E. F. and Bunnett, N. W. (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://doi.org/10.1074/jbc.M312090200
2003
- Rigoni, M., Trevisani, M., Gazzieri, D., Nadaletto, R., Tognetto, M., Creminon, C., Davis, J. B., Campi, B., Amadesi, S., Geppetti, P. and 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. S., Amadesi, S., Schmidlin, F. and Bunnett, N. (2003) Protease-activated receptor 2: activation, signalling and function. Biochemical Society Transactions, 31 (6). pp. 1191-1197. ISSN 1470-8752
2002
- Schmidlin, F., Amadesi, S., Dabbagh, K., Lewis, D. E., Knott, P., Bunnett, N. W., Gater, P. R., Geppetti, P., Bertrand, C. and Stevens, M. E. (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://doi.org/10.4049/jimmunol.169.9.5315
- Trevisani, M., Smart, D., Gunthorpe, M. J., Tognetto, M., Barbieri, M., Campi, B., Amadesi, S., Gray, J., Jerman, J. C., Brough, S. J., Owen, D., Smith, G. D., Randall, A. D., Harrison, S., Bianchi, A., Davis, J. B. and 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://doi.org/10.1038/nn0602-852
2001
- Schmidlin, F., Amadesi, S., Vidil, R., Trevisani, M., Martinet, N., Caughey, G., Tognetto, M., Cavallesco, G., Mapp, C., Geppetti, P. and Bunnett, N. W. (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://doi.org/10.1164/ajrccm.164.7.2101157
- Amadesi, S., Moreau, J., Tognetto, M., Springer, J., Trevisani, M., Naline, E., Advenier, C., Fisher, A., Vinci, D., Mapp, C., Miotto, D., Cavallesco, G. and 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://doi.org/10.1164/ajrccm.163.5.2002079
2000
- Ricciardolo, F. L., Steinhoff, M., Amadesi, S., Guerrini, R., Tognetto, M., Trevisani, M., Creminon, C., Bertrand, C., Bunnett, N. W., Fabbri, L. M., Salvadori, S. and 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://doi.org/10.1164/ajrccm.161.5.9907133
- Steinhoff, M., Vergnolle, N., Young, S. H., Tognetto, M., Amadesi, S., Ennes, H. S., Trevisani, M., Hollenberg, M. D., Wallace, J. L., Caughey, G. H., Mitchell, S. E., Williams, L. M., Geppetti, P., Mayer, E. A. and Bunnett, N. W. (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://doi.org/10.1038/72247