Brain is particularly vulnerable to toxic effects of reactive oxygen species and a clear correlation between neurodegeneration and oxidative stress has been observed. Iron is an essential element required for many physiological functions, but it is also a key player in oxidative stress induction. Therefore, we aim to characterize the physiological mechanisms of iron handling, both at cellular and mitochondrial level, in primary neurons and glial cells. Moreover, we are employing Induced Pluripotent Stem Cells (iPSCs) to investigate the molecular mechanisms underlying Friedreich’s ataxia, as well as other neurodegenerative disorders characterized by alteration of intracellular iron homeostasis.
1997 PhD in Pharmacology and Toxicology, School of Medicine, University of Milan
1992 Master’s degree in Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Milan
- Research and professional experiences
2013- Assistant professor in Physiology, Vita-Salute San Raffaele University
2000-13 Research associate, Cellular Neurophysiology Unit, S. Raffaele Scientific Institute
1998-99 Postdoctoral fellow, Cell Biology Department, Duke University Medical Center Durham, North Carolina, USA
1996-98 Postdoctoral fellow, Cellular Neurophysiology Unit S. Raffaele Scientific Institute
1992-96 Ph.D. student, Cellular Neurophysiology Unit, S. Raffaele Scientific Institute and Pharmacology Department, University of Milan
1990-92 Undergraduate student, Cardiovascular Unit, Farmitalia – C. Erba, Milan
- Teaching Appointment
2015-17 Assistant professor: course of Physiology, Dental School and course of Experimental Cell Biology and Bioimaging, II part, Medical School, Vita-Salute S. Raffaele University.
2013-14 Assistant professor , responsible for the course 0f Experimental Cell Biology and Bioimaging, II part t, Medical School, Vita-Salute S. Raffaele University.
2004-13 Adjunct Professor in Physiology, responsible for the course: “Saggi cellulari e bioimaging”, Medical School, Vita-Salute S. Raffaele University.
2000-03 Tutor in Physiology and Pharmacology Courses, Medical School, Vita-Salute S. Raffaele University.
-2017-2019: Italian Ministry of Research, Progetti di Ricerca di Interesse Nazionale (PRIN)
Project title: Early neuroprotective and anti-inflammatory treatment to prevent the development of diabetic
2017-2019: Lombardy Regional Authority
Project title: New biotechnological iPSC systems for the pharmaceutical development in neurodegenerative diseases
2017-2019: Lombardy Regional Authority
Project title: Platform for the identification of relevant pharmacological targets for the treatments of oncologic and CNS diseases
2014: National Ataxia Foundation (NAF)- Research grant
Project title: IPSC-derived neurons from Friedreich’s ataxia (FA) patients as a model to characterize pathological mechanisms and devise neuroprotective strategies
2012-2014: Friedreich’s Ataxia Research Alleance (FARA) –Research grant
Project title: Characterization of induced pluripotent stem cells from patients with Friedreich’s ataxia
1- Mechanisms of iron homeostasis in brain-derived primary cultures
This project is aimed to characterize iron handling and oxidative stress in brain derived primary cultures (neurons, glia). Molecular (gene silencing, RT-qPCR), biochemical (western blotting, subcellular fractionation, cellular assays) and advanced fluorescence optical approaches (Total Internal Reflection Microscopy and High Throughput Microscopy) will be employed, in order to study:
– the expression of molecules involved in intracellular iron import/homeostasis and its modulation under conditions of glial cell activation;
– the mechanisms of iron import and handling in mitochondria;
– the implications of synaptic activity and neuron-glia interaction on neuronal iron homeostasis;
– the evaluation of neurotoxic and the neuroprotective strategies in iron-induced neurodegeneration.
2- Role of intracellular iron dysregulation and oxidative stress in Friedreich’s ataxia
Friedreich’s ataxia is an autosomal recessive disease caused by a reduction of expression of frataxin, a ubiquitous mitochondrial protein involved in cellular iron homeostasis. In order to investigate the effects of frataxin deficiency on oxidative stress and neuronal survival, we employ single cell videomicroscopy approaches and fluorescent probes to monitor specific cellular parameters related to iron handling and cytotoxicity. We use neurons and glial cells derived from human Induced Pluripotent Stem Cell (iPSC) to overcome the known limitations of cellular and animal models.
- Codazzi F, Hu A, Rai M, Salerno Scarzella F, Mangiameli E, Pelizzoni I, Grohovaz F, Pandolfo M. Friedreich ataxia induced pluripotent stem cell-derived neurons show a cellular phenotype that is corrected by a benzamide HDAC inhibitor. Hum Mol Genet. 2016 [Epub ahead of print]
- Codazzi F, Pelizzoni I, Zacchetti D, Grohovaz F. Iron entry in neurons and astrocytes: a link with synaptic activity. Frontiers in Molecular Neuroscience 3: 8-18, 2015
- Maccarinelli F, Pagani A, Cozzi A, Codazzi F, Di Giacomo G, Capoccia S, Rapino S, Finazzi D, Politi LS, Cirulli F, Giorgio M, Cremona O, Levi S, Grohovaz F. A novel neuroferritinopathy mouse model (FTL 498InsTC) shows progressive brain iron dysregulation, morphological signs of early neurodegeneration and motor coordination deficits. Neurobiology of Disease 81:119-33, 2015
- Maltecca F, Baseggio E, Consolato F, Mazza D, Podini P, Young SM Jr, Drago I, Bahr BA, Puliti A, Codazzi F, Quattrini A, Casari G. Purkinje neuron Ca2+ influx reduction rescues ataxia in SCA28 model. J Clin Invest. J Clin Invest. 125(1):263-74, 2015
- Lazzaro M, Bettegazzi B, Barbariga M, Codazzi F, Zacchetti D, Alessio M. Ceruloplasmin potentiates nitric oxide synthase activity and cytokine secretion in activated microglia. J Neuroinflammation. 11(1):164, 2014
- Macco R, Pelizzoni I, Consonni A, Vitali I, Giacalone G, Martinelli Boneschi F, Codazzi F, Grohovaz F, Zacchetti D. Astrocytes acquire resistance to iron-dependent oxidative stress upon proinflammatory activation. J Neuroinflammation. 10:130, 2013
- Pelizzoni I, Zacchetti D, Campanella A, Grohovaz F, Codazzi F. Iron uptake in quiescent and inflammation-activated astrocytes: a potentially neuroprotective control of iron burden. Biochim Biophys Acta. 1832(8):1326-33, 2013
- Pelizzoni I, Zacchetti D, Smith CP, Grohovaz F, Codazzi F. Expression of divalent metal transporter 1 in primary hippocampal neurons: reconsidering its role in non-transferrin-bound iron influx. J Neurochem. 120:269-78, 2012
- Olivieri S, Conti A, Iannaccone S, Cannistraci CV, Campanella A, Barbariga M, Codazzi F, Pelizzoni I, Magnani G, Pesca M, Franciotta D, Cappa SF, Alessio M. Ceruloplasmin oxidation, a feature of Parkinson’s disease CSF, inhibits ferroxidase activity and promotes cellular iron retention. J Neurosci. 31:18568-772011, 2011
- Consonni A, Morara S, Codazzi F, Grohovaz F, Zacchetti D. Inhibition of lipopolysaccharide-induced microglia activation by calcitonin gene related peptide and adrenomedullin. Mol Cell Neurosci, 48:151-60, 2011
- Pelizzoni I, Macco R, Morini MF, Zacchetti D, Grohovaz F, and Codazzi F. Iron handling in hippocampal neurons: activity-dependent iron entry and mitochondria-mediated neurotoxicity. Aging Cell 10:172-83, 2011
- Bettegazzi B, Mihailovich M, Di Cesare A, Consonni A, Macco R, Pelizzoni I, Codazzi F, Grohovaz F and Zacchetti D β-secretase Activity in Rat Astrocytes: Translational Block of BACE1 and Modulation of BACE2 Expression. Eur. J. Neurosci,.33:236-43, 2011
- D’Antoni S, Zambusi L, Codazzi F, Zacchetti D, Grohovaz F, Provini L, Catania MV, Morara S. Calcitonin Gene-Related Peptide (CGRP) stimulates Purkinje cell dendrite growth in culture. Neurochemical Research 35:2135-43, 2010
- Pelizzoni I, Macco M, Zacchetti D, Grohovaz F, Codazzi F. Iron and calcium in central nervous system: a close relationship in health and sickness. Biochem. Soc. Trans., 36:1309-12, 2008
- Chiulli N, Codazzi F, Di Cesare A, Gravaghi C, Zacchetti D, Grohovaz F. Sphingosylphosphocholine effects on cultured astrocytes reveal mechanisms potentially involved in neurotoxicity in Niemann-Pick type A disease. Eur. J. Neurosci., 26(4):875-81, 2007
- Codazzi F, Di Cesare A, Chiulli N, Albanese A, Meyer T, Zacchetti D, Grohovaz F. Synergistic control of protein kinase Cgamma activity by ionotropic and metabotropic glutamate receptor inputs in hippocampal neurons. J Neurosci., 26(13):3404-11, 2006
- Negri L, Lattanzi R, Giannini E, Colucci MA, Mignogna G, Barra D, Grohovaz F, Codazzi F, Kaiser A, Kreil G, Melchiorri P. Biological activities of Bv8 analogues. Br J Pharmacol., 146(5):625-32, 2005
- Vangelista L, Soprana E, Cesco-Gaspere M, Mandiola P, Di Lullo G, Fucci RN, Codazzi F, Palini A, Paganelli G, Burrone OR, Siccardi AG. Membrane IgE binds and activates Fc epsilon RI in an antigen-independent manner. J Immunol., 174(9):5602-11, 2005
- Pietri Tonelli D, Mihailovich M, Di Cesare A, Codazzi F, Grohovaz F, Zacchetti D. Translational regulation of BACE-1 expression in neuronal and non-neuronal cells. Nucleic Acids Research, 32: 1808-1817, 2004
- Codazzi F, Teruel MN, Meyer T. Control of astrocyte Ca2+ oscillations and waves by oscillating translocation and activation of protein kinase C. Curr. Biol., 11: 1089-1097, 2001.
- Haugh JM, Codazzi F, Teruel M, Meyer T. Spatial sensing in fibroblasts mediated by 3′ phosphoinositide. J. Cell Biol., 151: 1269-1279, 2000
- Improta-Brears, T, Whorton AR, Codazzi F, York J.D, Meyer T, McDonnell PD. Estrogen-induced activation of mitogen-activated protein kinase requires mobilization of intracellular calcium. Proc Natl. Acad. Sci., USA 96:4686-4691, 1999
- Bertuzzi F, Davalli AM, Nano R, Socci C, Codazzi F, Fesce R, Di Carlo V, Pozza G, Grohovaz F. Mechanisms of Coordination of Ca2+ Signals in Pancreatic Islet Cells. Diabetes, 48: 1971-1978, 1999
- Martino G, Grohovaz F, Brambilla E, Codazzi F, Consiglio A, Clementi E, Filippi M, Comi G, Grimaldi LME. Proinflammatory cytokines regulate antigen-independent T cell activation by two separate calcium signaling pathways in multiple sclerosis patients. Ann. Neurol., 43 (3): 340-349, 1998
- Codazzi F, Racchetti G, Grohovaz F, Meldolesi J. Transduction signals induced in rat brain cortex astrocytes by the HIV-1 gp120. Febs Letters, 384:135-137, 1996
- Bastianutto C, Clementi E, Codazzi F, Podini P, De Giorgi F, Rizzuto R, Meldolesi J, Pozzan T. Overexpression of calreticulin increases the Ca2+ content of rapidly exchanging Ca2+ stores and reveals aspects of their lumenal microenvironment and function. J. Cell Biol., 130:847-855, 1995
- Lorenzon P, Zacchetti D, Codazzi F, Fumagalli G, Meldolesi J, Grohovaz F. Ca2+ waves in PC12 neurites: a bidirectional, receptor-oriented form of Ca2+ signalling. J.Cell Biol., 129:797-804, 1995
- Codazzi F, Menegon A, Zacchetti D, Ciardo A, Grohovaz F, Meldolesi J. HIV-1 gp120 glycopropein induces [Ca2+]i responses not only in type-2 but also in type-1 astrocytes and oligodendrocytes of rat cerbellum. Eur. J. Neurosci., 7: 1333-1341, 1995
- D’Andrea P, Codazzi F, Zacchetti D, Meldolesi J, Grohovaz F. Oscillations of cytosolic calcium in rat chromaffin cells: dual modulation in frequency and amplitude. Biochem. Biophys. Res. Comm., 205:1264-1269, 1994