neuroscience
Name: Dr Manuela Mengozzi
Academic position: Research Fellow in Neuroimmunology
Research: Neuroinflammation, interaction between inflammatory cytokines and neuroprotective factors
Contact details:
Trafford Centre for Medical Research
Brighton and Sussex Medical School
University of Sussex
Falmer, Brighton BN1 9RY,UK
Tel: +44(0)1273 873146
Fax: +44(0)1273 877576
Biography:
Doctor in Biological Sciences, University of Pisa, Italy, 1987
Specialist in Pharmacological Research, Mario Negri Institute, Milan, Italy, 1991
Postdoctoral Research Fellow, Picower Institute, Manhasset, NY, 1993-4
Postdoctoral Research Fellow, DIBIT, Milan, Italy, 1995-1998
Postdoctoral Research Fellow, Stanford University, 1998-2000
Research Focus:
Cellular targets and mechanisms of the antineuroinflammatory and neuroprotective action of erythropoietin.
Role of endogenous erythropoietin in experimental autoimmune encephalomyelitis, a model of multiple sclerosis and of neuroinflammation.
Current Research:
My research has always focused on cytokines and chemokines and their pathogenic and protective mechanisms in inflammation and infectious diseases.
Since 2000, I have been working on erythropoietin (EPO) as an antiinflammatory and neuroprotective cytokine, with a particular interest in the protection observed in experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS) and of neuroinflammation. At the moment, my interests are:
a) finding the cellular targets responsible for the antineuroinflammatory and neuroprotective action of EPO in EAE and MS. We are currently looking at the effect of EPO on endothelial cells in terms of antiinflammation and induction of neuroprotective factors and planning to study EPO effect on remyelination using oligodendrocyte precursor cells;
b) understanding the role of endogenous EPO in EAE and MS and how to upregulate endogenous EPO production in order to protect from the disease. I found and recently published that endogenous EPO is induced in the spinal cord in the course of EAE. We have preliminary data showing that retinoic acid is a strong upregulator of hypoxia-induced EPO in neuronal cells. Since retinoids have antiinflammatory and neuroprotective effects, I am particularly interested in understanding how these two endogenous systems of neuroprotection and antineuroinflammation are linked.
Key/recent publications:
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. (2008) Endogenous erythropoietin as part of the cytokine network in the pathogenesis of experimental autoimmune encephalomyelitis. Mol Med, 14(11-12): 682-8.
Taoufik E, Petit E, Divoux D, Tseveleki V, Mengozzi M, Roberts ML, Valable S, Ghezzi P, Quackenbush J, Brines M, Cerami A, Probert L. (2008) TNF receptor I sensitizes neurons to erythropoietin- and VEGF-mediated neuroprotection after ischemic and excitotoxic injury. Proc Natl Acad Sci USA 105(16): 6185-90.
Ghezzi P, Bigini P, Mengozzi M. (2006). Role of erythropoietin in inflammatory pathologies of the CNS. In: Erythropoietin and the nervous system. Ahmet Hoke (ed.). Springer Verlag, New York, chapter 12, pp. 1-19. Book chapter.
Mennini T, De Paola M, Bigini P, Mastrotto C, Fumagalli E, Barbera S, Mengozzi M, Viviani B, Corsini E, Marinovich M, Torup L, Van Beek J, Leist M, Brines M, Cerami A, Ghezzi P. (2006) Nonhematopoietic erythropoietin derivatives prevent motoneuron degeneration in vitro and in vivo. Mol Med 12(7-8):153-60.
Mengozzi M, Latini R, Salio M, Sfacteria A, Piedimonte G, Gerwien JG, Leist M, Siren AL, Ghezzi P, Chimenti S. (2006). Increased erythropoietin production after myocardial infarction in mice. Heart 92(6): 838-9.
Losana G, Bovolenta C, Rigamonti L, Borghi I, Altare F, Jouanguy E, Forni G, Casanova JL, Sherry B, Mengozzi M, Trinchieri G, Poli G, Gerosa F, Novelli F. (2002) IFN-gamma and IL-12 differentially regulate CC-chemokine secretion and CCR5 expression in human T lymphocytes. J Leukoc Biol 72(4): 735-42.
Mengozzi M, Malipatlolla M, De Rosa SC, Herzenberg LA, Herzenberg LA, Roederer M. (2001). Naive CD4 T cells inhibit CD28-costimulated R5 HIV replication in memory CD4 T cells. Proc Natl Acad Sci U S A 98(20):11644-9.
Cota M, Mengozzi M, Vicenzi E, Panina-Bordignon P, Sinigaglia F, Transidico P, Sozzani S, Mantovani A, Poli G. (2000). Selective inhibition of HIV replication in primary macrophages but not T lymphocytes by macrophage-derived chemokine. Proc Natl Acad Sci U S A 97(16):9162-7.
Mengozzi M, De Filippi C, Transidico P, Biswas P, Cota M, Ghezzi S, Vicenzi E, Mantovani A, Sozzani S, Poli G. (1999) Human immunodeficiency virus replication induces monocyte chemotactic protein-1 in human macrophages and U937 promonocytic cells. Blood 93(6): 1851-7.
Mengozzi M, Fantuzzi G, Faggioni R, Marchant A, Goldman M, Orencole S, Clark BD, Sironi M, Benigni F, Ghezzi P. (1994). Chlorpromazine specifically inhibits peripheral and brain TNF production, and up-regulates IL-10 production, in mice. Immunology 82(2): 207-10.
Re F, Mengozzi M, Muzio M, Dinarello CA, Mantovani A, Colotta F. (1993). Expression of interleukin-1 receptor antagonist (IL-1ra) by human circulating polymorphonuclear cells. Eur J Immunol 23(2): 570-3.
Poutsiaka DD, Mengozzi M, Vannier E, Sinha B, Dinarello CA. (1993) Cross-linking of the beta-glucan receptor on human monocytes results in interleukin-1 receptor antagonist but not interleukin-1 production. Blood 82(12):3695-700.
Mengozzi M, Ghezzi P. 1993. Cytokine down-regulation in endotoxin tolerance. Eur Cytokine Netw 4(2): 89-98. Review.
Mengozzi M, Ghezzi P. (1991). Defective tolerance to the toxic and metabolic effects of interleukin 1. Endocrinology 128(3):1668-72.
Mengozzi M, Sironi M, Gadina M, Ghezzi P. (1991). Reversal of defective IL-6 production in lipopolysaccharide-tolerant mice by phorbol myristate acetate. J Immunol 147(3):899-902.
Active collaborations:
Dr Janet Holley, Peninsula Medical School, Exeter
Dr Alexander Annenkov, Queen Mary University of London
Dr Monique Stins, Johns Hopkins, Baltimore, USA
Dr Barbara Viviani, University of Milan, Italy