Present position
• Full Professor of Biochemistry at the Dept. of Biology, Univ. of Rome “Tor Vergata”;
• Nominated member of the Commission for Amyotrophic Lateral Sclerosis of the Italian Ministry of Health.
• Elected member of the directing counsel of the Inter-University Centre for Research on the Molecular Basis of Neurodegenerative Diseases, Italy.
• Group leader of the laboratory for Neurochemistry at the Foundation Santa Lucia IRCCS, Roma

Memberships
The American Society for Biochemistry and Molecular Biology (ASBMB)
Italian Society for Biochemistry (SIB)
Italian Society for Neurosciences (SINS)
International Society for Neurochemistry (ISN)
European ALS Association (EALS)
Italian Network for the Study of Motor Neuron Disease
Inter-University Centre for Research on the Molecular Basis of Neurodegenerative Diseases, Italy
Member of the editorial board of The Open Biology Journal

Past work experience
1981 - 1983: visiting scientist at the Institute of Histology, Faculty of Sciences, University of Rome "La Sapienza", Italy
1983: visiting scientist (EMBO fellowship) at the Biozentrum, University of Basel, Switzerland
1984 - 1986: post-doctoral fellow at the Dept. of Genetics and Molecular Biology, Faculty of Sciences, University of Rome "La Sapienza" supported by fellowships from the Foundation Anna Villa Rusconi and the Foundation G. and L. Shenker.
1986 - 2001: Staff scientist at the Dept. of Biology, University of Rome “Tor Vergata”, Italy
2001-2006: Associate Professor of Biochemistry, Faculty of Sciences, University of Rome “Tor Vergata”, Italy
1996-2002 : Lectured the course of Cellular Biochemistry at the Faculty of Sciences, University of Rome “Tor Vergata”, Italy
1998- 2007 : Coordinator of the laboratories in the Centre for Experimental Neurobiology “Mondino–Tor Vergata” and group leader of the laboratory of Neurochemistry at the Fondazione Santa Lucia IRCCS, Rome, Italy


Main research topics
Prof. Carrì has more than 15 years’ experience with neurodegenerative processes caused by mutations in the SOD1 gene, the main cause of the familiar form of Amyotrophic Lateral Sclerosis (ALS). In particular, she is now studying mitochondrial alterations caused by aggregated mutant SOD1. She is author of about 80 publications in international peer reviewed journals, including more than 45 publications on the molecular mechanisms of ALS.
Past research interests include :
DNA replication and genome organisation (1981-1986)
Structure and function of the snRNAs (1983)
Structure and enzyme mechanism of Cu, Zn superoxide dismutase (1986-1996)
Regulation of the expression of Cu, Zn superoxide dismutase (1990-1994)
Copper metabolism in eukaryotes (1990 – today)
Pathogenesis of Alzheimer’s disease and Parkinson's disease (2000-today)

GRANTED by EC, ALS Association, Telethon, Fondation Thierry-Latran, AISLA, Fondazione Cariplo, MIUR, CNR, Min. Salute

Internazional Scientific Collaborations (active)
Prof. B. Keller – Univ. di Gottingen, Germania
Prof. J.-P. Loeffler - Université Louis Pasteur, Strasbourg, France
Dr. T. Achsel - KU Leuven, Belgium
Prof. J. Garcia. Sancho - Univ. Valladoilid - Spain

Ongoing projects :
1. Damage to mitochondria has emerged as a central feature that contributes to neurodegeneration in Amyotrophic Lateral Sclerosis (ALS). Recent evidence indicates that mitochondria are one of the primary location of damage inside motor neurons and astrocytes, which both contribute to the disease. Dysfunction of mitochondria is observed early in patients (and in experimental models for ALS) and causes the death of neurons, which underlies onset of paralysis and death of patients (Cozzolino et al., 2008).
Mitochondria are ‘the powerhouse of the cell’ because of their ability to convert nutrients into ATP and they also play an essential role in intermediate metabolism and in maintaining cellular Ca2+ homeostasis. However, mitochondria are also the main source of reactive oxygen species (ROS) and function as gatekeepers in the intrinsic apoptotic processes. Thus, mitochondrial dysfunction can result in cell death, either by bioenergetics failure, oxidative stress or apoptosis.
In this project, we propose to attempt rescue of correct mitochondria function in experimental models for SOD1-linked familial ALS by genetic manipulation of the p66Shc-dependent molecular pathway which underlies oxidative stress and mitochondrial damage in cells.
Indeed, a novel signaling mechanism involving the 66-kilodalton isoform of the growth factor adapter Shc (p66Shc), that is operative in the pathophysiological condition of oxidative stress, has been recently identified. The protein p66Shc is an alternatively spliced isoform of a growth factor adapter that is phosphorylated upon oxidative stress. In this form, a fraction of p66Shc localizes to mitochondria, where it binds to cytochrome c and acts as oxidoreductase, generating reactive oxygen species (ROS) and leading to organelle dysfunction and cell death (Giorgio et al., 2005; Pinton et al., 2007). p66Shc-/- mice exhibit a 30% extended lifespan, reduced H2O2 levels, and an enhanced resistance against oxidative stress, indicating that p66Shc acts as a key molecular sentinel that controls cellular stress responses and mammalian lifespan (Migliaccio et al., 1999).
Taking advantage of the p66Shc-/- mice model, which will be available in our lab, we will assess whether it is possible to prevent neuronal damage through preservation of mitochondrial functionality in mutant SOD1 mice. Up to date no effective therapy exists for ALS and only support treatment is administered to patients, that invariably die a few years after onset of symptoms. Individuation of new strategies to intercept damage due to the action of mutant SOD1 on mitochondria may allow devising new therapeutic approaches.

2. The objective of this study is to understand whether rescue of mitochondrial damage in ALS is possible through the modulation of the Rac1 pathway.
Rac1 is a member of the Rho family of small GTPases that regulate multiple signaling pathways controlling the organization of cytoskeleton, gene expression, and cell proliferation. Rac1 is also an essential regulator of NADPH-dependent membrane oxidase (NOX) that produces superoxide anions.
In a previous study we have demonstrated that 1. expression of mutant SOD1 in neuronal cells is accompanied by decreased activity of Rac1; 2. Rac1 inhibition is oxidative in nature and possibly linked to mitochondrial damage; 3. expression of a constitutively active, dominant form Rac1 protects neuronal cells from mutSOD1-induced mitochondrial damage and apoptosis. Thus, activation of Rac1 seems a promising target for ALS treatment.
Specific aims of this study are:
1. to understand whether and how alteration of the Rac1 pathway is linked to neurodegeneration in vitro and in vivo in different models for familial ALS;
2. to attempt rescue of neuronal cells expressing fALS mutant proteins through genetic manipulation of Rac1;
3. to attempt rescue of G93A-SOD1 mice by treatment with Cytotoxic Necrotizing Factor 1 (CNF1), a bacterial protein endowed with Rho GTPase activating properties.
Results from this study may allow collecting further evidence that it is possible to prevent neuronal damage through preservation of mitochondrial functionality and help to devise new strategies for the therapy of ALS.

Selected, last 5 years :

1: Iaccarino C, Mura ME, Esposito S, Carta F, Sanna G, Turrini F, Carrì MT,
Crosio C. Bcl2-A1 interacts with pro-caspase-3: Implications for amyotrophic
lateral sclerosis. Neurobiol Dis. 2011 May 25. [Epub ahead of print]
2: Crosio C, Valle C, Casciati A, Iaccarino C, Carrì MT. Astroglial inhibition of NF-κB does not ameliorate disease onset and progression in a mouse model for
amyotrophic lateral sclerosis (ALS). PLoS One. 2011 Mar 18;6(3):e17187.
3:Lenzken SC, Romeo V, Zolezzi F, Cordero F, Lamorte G, Bonanno D, Biancolini D,Cozzolino M, Pesaresi MG, Maracchioni A, Sanges R, Achsel T, Carrì MT, Calogero RA, Barabino SM. Mutant SOD1 and mitochondrial damage alter expression and splicing of genes controlling neuritogenesis in models of neurodegeneration. Hum Mutat. 2011 Feb;32(2):168-82.
4: Ferri A, Fiorenzo P, Nencini M, Cozzolino M, Pesaresi MG, Valle C, Sepe S,
Moreno S, Carrì MT. Glutaredoxin 2 prevents aggregation of mutant SOD1 in
mitochondria and abolishes its toxicity. Hum Mol Genet. 2010 Nov
15;19(22):4529-42.
5: Loizzo S, Pieri M, Ferri A, Carrì MT, Zona C, Fortuna A, Vella S. Dynamic
NAD(P)H post-synaptic autofluorescence signals for the assessment of
mitochondrial function in a neurodegenerative disease: monitoring the primary
motor cortex of G93A mice, an amyotrophic lateral sclerosis model. Mitochondrion. 2010 Mar;10(2):108-14.
6: Arciello M, Capo CR, Cozzolino M, Ferri A, Nencini M, Carrì MT, Rossi L.
Inactivation of cytochrome c oxidase by mutant SOD1s in mouse motoneuronal NSC-34 cells is independent from copper availability but is because of nitric oxide. J Neurochem. 2010 Jan;112(1):183-92.
7: D'Ambrosi N, Finocchi P, Apolloni S, Cozzolino M, Ferri A, Padovano V,
Pietrini G, Carrì MT, Volonté C. The proinflammatory action of microglial P2
receptors is enhanced in SOD1 models for amyotrophic lateral sclerosis. J
Immunol. 2009 Oct 1;183(7):4648-56.
8: Kupershmidt L, Weinreb O, Amit T, Mandel S, Carri MT, Youdim MB.
Neuroprotective and neuritogenic activities of novel multimodal iron-chelating
drugs in motor-neuron-like NSC-34 cells and transgenic mouse model of amyotrophic lateral sclerosis. FASEB J. 2009 Nov;23(11):3766-79.
9: Jaiswal MK, Zech WD, Goos M, Leutbecher C, Ferri A, Zippelius A, Carrì MT,
Nau R, Keller BU. Impairment of mitochondrial calcium handling in a mtSOD1 cell
culture model of motoneuron disease. BMC Neurosci. 2009 Jun 22;10:64.
10: Bendotti C, Carrì MT. Amyotrophic lateral sclerosis: mechanisms and
countermeasures. Antioxid Redox Signal. 2009 Jul;11(7):1519-22.
11: Cozzolino M, Pesaresi MG, Amori I, Crosio C, Ferri A, Nencini M, Carrì MT.
Oligomerization of mutant SOD1 in mitochondria of motoneuronal cells drives
mitochondrial damage and cell toxicity. Antioxid Redox Signal. 2009 Jul;11(7):1547-58.
12: Pizzasegola C, Caron I, Daleno C, Ronchi A, Minoia C, Carrì MT, Bendotti C.
Treatment with lithium carbonate does not improve disease progression in two
different strains of SOD1 mutant mice. Amyotroph Lateral Scler. 2009
Aug;10(4):221-8.
13: Ferri A, Nencini M, Cozzolino M, Carrara P, Moreno S, Carrì MT. Inflammatory
cytokines increase mitochondrial damage in motoneuronal cells expressing mutant
SOD1. Neurobiol Dis. 2008 Dec;32(3):454-60.
14: Ferraro E, Pulicati A, Cencioni MT, Cozzolino M, Navoni F, di Martino S,
Nardacci R, Carrì MT, Cecconi F. Apoptosome-deficient cells lose cytochrome c
through proteasomal degradation but survive by autophagy-dependent glycolysis.
Mol Biol Cell. 2008 Aug;19(8):3576-88.
15: Cozzolino M, Ferri A, Carrì MT. Amyotrophic lateral sclerosis: from current
developments in the laboratory to clinical implications. Antioxid Redox Signal.
2008 Mar;10(3):405-43.
16: Carrì MT. Minocycline for patients with ALS. Lancet Neurol. 2008 Feb;7(2):118-9.
17: Cozzolino M, Amori I, Pesaresi MG, Ferri A, Nencini M, Carrì MT. Cysteine 111 affects aggregation and cytotoxicity of mutant Cu,Zn-superoxide dismutase
associated with familial amyotrophic lateral sclerosis. J Biol Chem. 2008 Jan
11;283(2):866-74.
18: Iaccarino C, Crosio C, Vitale C, Sanna G, Carrì MT, Barone P. Apoptotic
mechanisms in mutant LRRK2-mediated cell death. Hum Mol Genet. 2007 Jun
1;16(11):1319-26.
19: Celsi F, Svedberg M, Unger C, Cotman CW, Carrì MT, Ottersen OP, Nordberg A,
Torp R. Beta-amyloid causes downregulation of calcineurin in neurons through
induction of oxidative stress. Neurobiol Dis. 2007 May;26(2):342-52.
20: Maracchioni A, Totaro A, Angelini DF, Di Penta A, Bernardi G, Carrì MT,
Achsel T. Mitochondrial damage modulates alternative splicing in neuronal cells:
implications for neurodegeneration. J Neurochem. 2007 Jan;100(1):142-53.

No projects are available to students for the current accademic year.