Amadesi, Silvia - University of Reading

研究领域

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.

近期论文

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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: 10.1074/jbc.M112.438184 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: 10.1161/CIRCULATIONAHA.111.089763 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: 10.1016/j.pharmthera.2010.10.002 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: 10.1152/ajpgi.00433.2009