neuroscience
Name: Professor Pietro Ghezzi
Academic position: Chair of Experimental Medicine; Head of Division of Clinical and Laboratory Investigation
Contact details:
Brighton and Sussex Medical School
Trafford Centre for Medical Research
University of Sussex
Falmer, Brighton BN1 9RY, UK
Tel: +44 (0) 1273 873112
Research
Biochemical mediators of inflammation (cytokines) with particular focus on the pathogenesis of ischemia reperfusion injury and neuroinflammation, and their pharmacological modulation with anti-inflammatory or neurotrophic factors.
Role of protein oxidation/reduction in the pathogenesis of inflammation and autoimmunity.
Biography
-PhD (Pharmacology) 2006
-Research Associate at Stanford University, Department of Genetics, with professor Len Herzenberg (1998-2000).
-Head, Laboratory of Neuroimmunology, "Mario Negri" Institute, Milan, Italy (1991-2008).
Research Focus
The biochemical mediators of innate immunity, including cytokines interleukin-1 (IL-1) and tumor necrosis factor (TNF) are produced as a response of the immune system to danger signals and are important mediators in the pathogenesis of inflammatory diseases, including diseases of the central nervous system. However the body responds to injury with the production of other mediators, including anti-inflammatory mediators and trophic factors, which limit the extension of damage and promote repair.
We study the complex network that regulates production of all these factors with the aim of redirecting the response in a sense more favourable to the host.
In particular, we have been interested in characterizing the neuro-protective, anti-inflammatory and neurotrophic action of erythropoietin, a mediator whose production is increased by the lack of oxygen in some tissues, such as that occurring during inflammation or ischemia.
We are also studying the role of oxidoreductive processes in inflammatory diseases. Tissue injury is often associated with oxidoreduction imbalance. However, although the concept of oxidative stress is very popular, there are not antioxidant drugs approved for use as clinical trials with antioxidants in the therapy or prevention of diseases have often produced contrasting results. We believe that this is due to the fact that these processes are not only involved in the onset or progression of tissue damage but have rather a regulatory significance. We have successfully applied state-of-the-art technologies, including proteomics and microarrays, to identify these regulatory functions of oxidoreduction processes, with particular interest on oxidoreduction of protein thiols/disulfides, and of reactive oxygen species.
PhD students
Ilaria Cervellini
Sonia Salzano
Active Collaborations
Arne Holmgren (Karolinska Institutet, Stockholm)
Kevin J. Tracey (Feinstein Institute, Manhasset, NY)
Paolo Di Simplicio (University of Siena)
Alberto Mantovani (Istituto Humanitas-University of Milan)
Anthony Cerami (Warren Instiutute, Ossining, NY)
Key papers (from over 200)
Mengozzi M, Cervellini I, Bigini P, Martone S, Biondi A, Pedotti R, Gallo B, Barbera S, Mennini T, Boraso M, Marinovich M, Petit E, Bernaudin M, Bianchi R, Viviani B, Ghezzi P. Endogenous Erithropoietin as Part of the Cytokine Network in the Pathogenesis of Experimental Autoimmune Encephalomyelitis. Mol Med. Mol Med. 2008 14:682-8
Ghezzi P, Di Simplicio P. Glutathionylation pathways in drug response. Curr Opin Pharmacol. 20077(4):398-403. Review.
Savino C, Pedotti R, Baggi F, Ubiali F, Gallo B, Nava S, Bigini P, Barbera S, Fumagalli E, Mennini T, Ghezzi P..: Delayed administration of erythropoietin and its non-erythropoietic derivatives ameliorates chronic murine autoimmune encephalomyelitis. J Neuroimmunol 2006, 172:27-37.
Laragione T, Gianazza E, Tonelli R, Bigini P, Mennini T, Casoni F, Massignan T, Bonetto V, Ghezzi P: Regulation of redox-sensitive exofacial protein thiols in CHO cells. Biol Chem 2006, 387:1371-1376.
Ghezzi P, Casagrande S, Massignan T, Basso M, Bellacchio E, Mollica L, Biasini E, Tonelli R, Eberini I, Gianazza E, et al.: Redox regulation of cyclophilin A by glutathionylation. Proteomics 2006, 6:817-825.
Sozzani S, Bosisio D, Mantovani A, Ghezzi P: Linking stress, oxidation and the chemokine system. Eur J Immunol 2005, 35:3095-3098.
Ghezzi P: Oxidoreduction of protein thiols in redox regulation. Biochem Soc Trans 2005, 33:1378-1381.
Fratelli M, Goodwin LO, Orom UA, Lombardi S, Tonelli R, Mengozzi M, Ghezzi P: Gene expression profiling reveals a signaling role of glutathione in redox regulation. Proc Natl Acad Sci U S A 2005, 102:13998-14003.
Leist M, Ghezzi P, Grasso G, Bianchi R, Villa P, Fratelli M, Savino C, Bianchi M, Nielsen J, Gerwien J, et al.: Derivatives of erythropoietin that are tissue protective but not erythropoietic. Science 2004, 305:239-242.
Fratelli M, Gianazza E, Ghezzi P: Redox proteomics: identification and functional role of glutathionylated proteins. Expert Rev Proteomics 2004, 1:365-376.
Bianchi R, Buyukakilli B, Brines M, Savino C, Cavaletti G, Oggioni N, Lauria G, Borgna M, Lombardi R, Cimen B, and Ghezzi P Erythropoietin both protects from and reverses experimental diabetic neuropathy. Proc Natl Acad Sci U S A 2004, 101:823-828.
Agnello D, Mascagni P, Bertini R, Villa P, Senaldi G, Ghezzi P: Granulocyte colony-stimulating factor decreases tumor necrosis factor production in whole blood: role of interleukin-10 and prostaglandin E(2). Eur Cytokine Netw 2004, 15:323-326.
Villa P, Bigini P, Mennini T, Agnello D, Laragione T, Cagnotto A, Viviani B, Marinovich M, Cerami A, Coleman TR, and Ghezzi P: Erythropoietin selectively attenuates cytokine production and inflammation in cerebral ischemia by targeting neuronal apoptosis. J Exp Med 2003, 198:971-975.
Laragione T, Bonetto V, Casoni F, Massignan T, Bianchi G, Gianazza E, Ghezzi P: Redox regulation of surface protein thiols: identification of integrin alpha-4 as a molecular target by using redox proteomics. Proc Natl Acad Sci U S A 2003, 100:14737-14741.
Ghezzi P, Bonetto V: Redox proteomics: identification of oxidatively modified proteins. Proteomics 2003, 3:1145-1153.
Fratelli M, Demol H, Puype M, Casagrande S, Villa P, Eberini I, Vandekerckhove J, Gianazza E, Ghezzi P: Identification of proteins undergoing glutathionylation in oxidatively stressed hepatocytes and hepatoma cells. Proteomics 2003, 3:1154-1161.
Ghezzi P, Romines B, Fratelli M, Eberini I, Gianazza E, Casagrande S, Laragione T, Mengozzi M, Herzenberg LA, Herzenberg LA: Protein glutathionylation: coupling and uncoupling of glutathione to protein thiol groups in lymphocytes under oxidative stress and HIV infection. Mol Immunol 2002, 38:773-780.
Fratelli M, Demol H, Puype M, Casagrande S, Eberini I, Salmona M, Bonetto V, Mengozzi M, Duffieux F, Miclet E, et al.: Identification by redox proteomics of glutathionylated proteins in oxidatively stressed human T lymphocytes. Proc Natl Acad Sci U S A 2002, 99:3505-3510.
Casagrande S, Bonetto V, Fratelli M, Gianazza E, Eberini I, Massignan T, Salmona M, Chang G, Holmgren A, Ghezzi P: Glutathionylation of human thioredoxin: a possible crosstalk between the glutathione and thioredoxin systems. Proc Natl Acad Sci U S A 2002, 99:9745-9749.
Siren AL, Fratelli M, Brines M, Goemans C, Casagrande S, Lewczuk P, Keenan S, Gleiter C, Pasquali C, Capobianco A, Mennini T , Cerami A, and Ghezzi P: Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress. Proc Natl Acad Sci U S A 2001, 98:4044-4049.
Bertini R, Howard OM, Dong HF, Oppenheim JJ, Bizzarri C, Sergi R, Caselli G, Pagliei S, Romines B, Wilshire JA, Herzenberg LA and Ghezzi P.: Thioredoxin, a redox enzyme released in infection and inflammation, is a unique chemoattractant for neutrophils, monocytes, and T cells. J Exp Med 1999, 189:1783-1789.