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Fabio Benfenati

Senior Researcher - Center Coordinator
Center Director

Center

NSYN@Unige Genova

Contacts

Largo Rosanna Benzi 10
+39 010 5558 447

About

PERSONAL DATA

Date and Place of Birth: November 5, 1954, Bologna (Italy)

Nationality and Status: Italian citizen, married, two children

CURRENT POSITION

Director, Center for Synaptic Neuroscience and Technology, The Italian Institute of Technology

Full professor of Neurophysiology, University of Genova Medical School

Adjunct Professor, The Rockefeller University, New York, NY, USA

Head, Laboratory of Molecular and Cellular Neurophysiology, University of Genova

Coordinator, Ph.D. Curriculum in Neuroscience and Brain Technologies, PhD Course in Neuroscience, University of Genova

EDUCATION

1973:“Enrico Fermi” High School, Bologna (Italy) Degree: Baccalaureate (60/60)

1979: University of Bologna, School of Medicine Degree: Doctor of Medicine (110/110 cum laude)

Field of Study: Neurochemistry

1983: University of Bologna, School of Medicine, Postdoctoral School of Neurology

Degree: Specialist in Neurology Field of Study: Neurophysiology

PROFESSIONAL EXPERIENCES

1980-1983: "Accademia Nazionale dei Lincei" fellow at the "Mario Negri" Institute (Milano, Italy)

1983-1984: Post-doctoral fellow at the Dept. of Histology and Neurobiology at the Karolinska Institutet, Stockholm (Sweden) in Kjell Fuxe’s and Thomas Hokfelt’s laboratories

1986-1989: Fogarty Fellow & Research Associate, Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York (USA) directed by Prof. Paul Greengard (Nobel Laureate in 2000)

1990-present: Member of the Adjunct Faculty, The Rockefeller University, New York (USA)

1992-1999: Associate Professor of Physiology, University of Roma, School of Medicine (Italy)

2000-present: Full Professor of Neurophysiology, University of Genova, School of Medicine (Italy)

2006-2015: Director, Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova (Italy)

2015-present: Director, Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, Genova (Italy)

 

Other Professional Experiences

1992-1996: Board Member of the Italian Society for Neuroscience

2003-2005: President, Italian Society for Neuroscience

2008-2011: Chairman, International Program Committee, 8th IBRO World Congress, Florence (Italy)

2009-2011: President, The Italian Physiological Society

2009-2012: Member, CNRS Conseil Scientifique du Dept. Sciences du Vivant, Paris (France)

2010-present: Member, International Scientific Council of the European Brain Research Institute, Rome

2005-present: Member, Scientific Committee of the International Genoa Science Festival

2012-present: President, Italian Collegium of Physiologists

2012-present: President, Advisory Board of the Clinical Research Institute of Neurological Sciences, Bologna (Italy)

2014-2016: Member of the Program Committee, Federation of the European Neuroscience Societies (FENS) Forum 2016, Copenhagen (Denmark)

RESEARCH ACTIVITY

Author of  > 250 research papers in peer-reviewed international journals, including: Science (1), Nature (2), Neuron (2), Nature Comm. (3), Nature Neuroscience (1), J. Cell Biology (5), J. Clin. Invest. (1), EMBO J. (2), Proc. Natl. Acad. Sci. USA (10), J. Neuroscience (11) and of 5 patents. Bibliometric parameters: Citations: 15193; h-Index: 66; i10-Index: 224 (Gogle Scholar)

EDITORIAL AND REVIEWER ACTIVITY

1. Associate Editor, Frontiers in Neuroscience – Section Neural Technology, The Frontiers Journals

2. Reviewer for National and international agencies (HFSP, NSF, Yale University, UK, Ireland, Norway, Singapore and Italian Research Councils, BBSRC-UK, Israel Science Foundation, Telethon, MIUR, INSERM-ANR).

2. Reviewer for International scientific journals (Nature, Nat. Phot., J. Cell Biol., Proc. Natl. Acad. Sci.  (USA, J. Neurosci., J. Neurochem., J. Cell Sci., Cell Death Diff., and many other journals).

MAIN SCIENTIFIC CONTRIBUTIONS

The main subjects of investigation of Dr. Benfenati in the last 30 years have been the molecular mechanisms of information transfer among neurons. He has begun working in the field of synaptic transmission in Paul Greengard’s laboratory in 1986. Since then, he has addressed the mechanisms of neural and synaptic communication using a variety of experimental models of human diseases by using a combination of experimental techniques ranging from cell biology, biochemistry, biophysics, live imaging, electrophysiology and molecular biology, providing the following main contributions: (i) Elucidation of the mechanisms of neurotransmitter release, synaptic vesicle trafficking and synaptic plasticity and identification of the proteins involved. A long array of papers has, for the first time, put forward the functional role of synaptic vesicle proteins in the regulation of the multi-step process of neurotransmitter release; (ii) Composition of the molecular machine that promotes membrane fusion during exocytosis and identification of the intracellular targets of tetanus/botulinum neurotoxins; (iii) Pathogenic mechanisms of synaptopathies in genetically altered mice lacking synaptic vesicle proteins as models of human neurological disorders such as epilepsy and autism; (iv) Generation of engineered neuronal networks, neuro-electronic and opto-neural interfaces by exploiting optogenetics and photovoltaic interfaces; (v) Study of the biocompatibility of graphene and graphene-related materials with neural tissue, with emphasis on the physiological effects of graphene-neuron interfaces. The double background of neurologist and cellular neurophysiologist allowed dr. Benfenati to get in depth into the cellular mechanisms that underlie normal brain function and whose dysfunction leads to the pathogenesis of neurological diseases. Fabio Benfenati is also active in scientific divulgation of Neurosciences and routinely gives talks at science festivals and at other public events.

Projects

2011-present:

- Horizon 2020. Call: H2020-MSCA-ITN-2014. “Extracellular Matrix in Epileptogenesis”. Role: PI (2015-2018)

- Cariplo Foundation 2012 Technology Call. PROJECT: "UMANA: Ultrasensitive Magnetic Array for recording of Neuronal Activity". Role: PI (2014-16)

- FP7-NMP-2013-EU-China. "Neuroscaffolds: Rapid prototyping scaffolds for the nervous system". Role: PI (2013/16)

- The Michael Stern Parkinson’s Research Foundation Foreign Research Award "Role of synaptic vesicle trafficking and presynaptic dysfunction in Parkinson disease". Role: PI (2013)

- EU Horizon 2020 - Flagship Graphene Rump-up "WP4: Health and Safety of graphene-based materials". Role: PI (2014/15)

- EU Horizon 2020 - Flagship Graphene Core 1 "WP4: Health and Environment". Role: PI (2016/17)

- EU Horizon 2020 - Flagship Graphene Core 1"WP5: "Biomedical Technologies". Role: PI (2016/17)

- CURE Epilepsy Innovator Grant "Optogenetic Regulation of the Transcription of Epilepsy Genes: an Innovative Strategy to Cure Drug-Resistant Epilepsy" (2013/14): Role: PI

- Telethon Foundation, Italy. GGP 14022: "Development and implant of the photovoltaic artificial retina in the pig with photoreceptor degeneration: towards the human Phase1 experimentation”. Role: PI (2015/16)

- EU FP7 - Health Epilepsy - "DESIRE: Development and Epilepsy - Strategies for Innovative Research to improve diagnosis, prevention and treatment in children with difficult to treat Epilepsy". Role: PI, Coordinator of WP5 (2013/2017)

- Telethon Foundation. Multicentre Project GGP 13033: “Role of the novel presynaptic protein PRRT2 in neuronal physiology and in the pathogenesis of paroxysmal neurological disorders”. Role: Coordinator (2013/15)

- Italian Ministry of Research - PRIN Multicentre Project “Excitatory/inhibitory balance in the central nervous system: synaptic transmission, plasticity and synaptopathies”. Role: Coordinator (2013/15)

- FP7-PEOPLE-2011-ITN Marie Curie. “OLIMPIA: Organic Optoelectronics integrated with living systems for neuroscience fundamental investigations and applications”. Role: PI (2012-2015)

- Telethon Foundation. GGP12033 New therapeutic approaches to Retinitis Pigmentosa” Role: PI (2013-2014)

- FP7 ICT-2009 8.7 - FET proactive 7– STREP Project: “FOCUS: Single Molecule Activation and Computing”. Role: PI (2011/13)

- MIUR PRIN “Role of synapsins in the control of synaptic transmission and plasticity: implications in the pathogenesis of epilepsy and autism”. Role: PI (2011/12)

- S. Paolo Foundation. “Information transfer in the CNS: from synaptic plasticity to the pathogenesis of brain diseases”. Role: Coordinator (2010/12)

- Telethon Foundation. Multicentre Project GGP09134 “Involvement of synapsin genes in epilepsy and autism”. Role: Coordinator (2010/12)

Selected Publications

 

SELECTED PUBLICATIONS IN REFEREED JOURNALS

 

2011-2016

Bramini M, Sacchetti S, Armirotti A, Rocchi A, Vázquez E, León Castellanos V, Bandiera T, Cesca F, Benfenati F (2016) Graphene Oxide Nanosheets Disrupt Lipid Composition, Ca2+ Homeostasis And Synaptic Transmission In Primary Cortical Neurons. ACS Nano 10: 7154-7171.

Antognazza MR, Di Paolo M, Ghezzi D, Mete M, Di Marco S, Maya-Vetencourt JF, Maccarone R, Desii A, Di Fonzo F, Bramini M, Russo A, Laudato L, Donelli I, Cilli M, Freddi G, Pertile G, Lanzani G, Bisti S, Benfenati F (2016) Characterization of a Polymer-Based, Fully Organic Prosthesis for Implantation into the Subretinal Space of the Rat. Adv Healthc Mater. 2016 May 30. doi: 10.1002/adhm.201600318 [Epub ahead of print].

Paonessa F, Criscuolo S, Sacchetti S, Amoroso D, Scarongella H, Pecoraro Bisogni F, Carminati E, Pruzzo G, Maragliano L, Cesca F, Benfenati F (2016) Regulation of neural gene transcription by optogenetic inhibition of the RE1-silencing transcription factor. Proc Natl Acad Sci USA 113: E91-100. 

Colombo E, Feyen P, Antognazza MR, Lanzani G, Benfenati F (2016) Nanoparticles: A Challenging Vehicle for Neural Stimulation. Front Neurosci. 10:105.

Perlini LE, Benfenati F, Cancedda L (2016) Synapsin III in brain development. Oncotarget 7: 15288-15289.

Valente P, Lignani G, Medrihan L, Bosco F, Contestabile A, Lippiello P, Ferrea E, Schachner M, Benfenati F, Giovedì S, Baldelli P (2016) Cell adhesion molecule L1 contributes to neuronal excitability regulating the function of voltage-gated Na+ channels. J Cell Sci. 129: 1878-1891.

Feyen P, Colombo E, Endeman D, Nova M, Laudato L, Martino N, Antognazza MR, Lanzani G, Benfenati F*, Ghezzi D* (2016) Light-evoked hyperpolarization and silencing of neurons by conjugated polymers. Sci Rep. 6: 22718.

Valente P, Castroflorio E, Rossi P, Fadda M, Sterlini B, Cervigni RI, Prestigio C, Giovedì S, Onofri F, Mura E, Guarnieri F, Antonella Marte A, Orlando M, Zara F, Fassio A, Valtorta F, Baldelli P, Corradi AM, Benfenati F (2016) PRRT2 is a key component of the Ca2+-dependent neurotransmitter release machinery. Cell Rep. 15: 117-131.

Rossi P, Sterlini B, Castroflorio E, Marte A, Onofri F, Valtorta F, Maragliano L, Corradi A, Benfenati F (2016) A novel topology of proline-rich transmembrane protein 2 (PRRT2): hints for an intracellular function at the synapse. J Biol Chem. 291: 6111-6123. 

Fassio A, Fadda M, Benfenati F (2016) Molecular machines determining the fate of endocytosed synaptic vesicles in nerve terminals. Front Synaptic Neurosci. 8: 10. 

Tagliatti E, Fadda M, Falace A, Benfenati F, Fassio A (2016) Arf6 regulates the cycling and the readily releasable pool of synaptic vesicles at hippocampal synapse. Elife Jan 5;5. pii: e10116. 

Piepgras J, Höltje M, Otto C, Harms H, Satapathy A, Cesca F, Benfenati F, Gitler D, Pich A, Zander JF, Ahnert-Hilger G, Ruprecht K (2015) Intrathecal immunoglobulin A and G antibodies to synapsin in a patient with limbic encephalitis. Neurol. Neuroimmunol. Neuroinflamm. 2: e169.

Colasante G, Lignani G, Rubio A, Medrihan L, Yekhlef L, Sessa A, Massimino L, Giannelli SG, Sacchetti S, Caiazzo M, Leo D, Alexopoulou D, Dell'Anno MT, Ciabatti E, Orlando M, Studer M, Dahl A, Gainetdinov RR, Taverna S, Benfenati F, Broccoli V (2015) Rapid conversion of fibroblasts into functional forebrain GABAergic interneurons by direct genetic reprogramming. Cell Stem Cell 17: 719-734.

Valente P, Orlando M, Raimondi A, Benfenati F, Baldelli P (2016) Fine tuning of synaptic plasticity and filtering by GABA released from hippocampal autaptic granule cells. Cereb. Cortex 26:1149-1167.

Piccini A, Perlini LE, Cancedda L, Benfenati F*, Giovedì S* (2015) Phosphorylation by PKA and Cdk5 Mediates the Early Effects of Synapsin III in Neuronal Morphological Maturation. J. Neurosci. 35: 13148-13159. * last co-authors

Antognazza MR, Martino N, Ghezzi D, Feyen P, Colombo E, Endeman D, Benfenati F, Lanzani G (2015) Shedding light on living cells. Adv. Mater. 27: 7662-7669.

Nguyen DK, Rouleau I, Sénéchal G, Ansaldo AI, Gravel M, Benfenati F, Cossette P (2015) X-linked focal epilepsy with reflex bathing seizures: Characterization of a distinct epileptic syndrome. Epilepsia 56: 1098-1108.

Cesca F, Satapathy A, Ferrea E, Nieus T, Benfenati F, Scholz-Starke J (2015) Functional Interaction between the Scaffold Protein Kidins220/ ARMS and Neuronal Voltage-Gated Na+ Channels. J. Biol. Chem. 290: 18045-18055.

Espinoza S, Lignani G, Caffino L, Maggi S, Sukhanov I, Leo D, Mus L, Emanuele  M, Ronzitti G, Harmeier A, Medrihan L, Sotnikova TD, Chieregatti E, Hoener MC, Benfenati F, Tucci V, Fumagalli F, Gainetdinov RR (2015) TAAR1 modulates cortical glutamate NMDA receptor function. Neuropsychopharmacol. 40: 2217-2227.

Zaltieri M, Grigoletto J, Longhena F, Navarria L, Favero G, Castrezzati S, Colivicchi MA, Corte LD, Rezzani R, Pizzi M, Benfenati F, Spillantini MG, Missale C, Spano P, Bellucci A (2015) Alpha-synuclein and synapsin III cooperatively regulate synaptic function in dopamine neurons. J. Cell Sci. 128: 2231-2243.

Perlini LE, Szczurkowska J, Ballif BA, Piccini A, Sacchetti S, Giovedì S, Benfenati F*, Cancedda L* (2015) Synapsin III acts downstream of semaphorin 3A/CDK5 signaling to regulate radial migration and orientation of pyramidal neurons in vivo. Cell Rep. 11: 234-248. * last co-authors

Martino N, Feyen P, Porro M, Bossio C, Zucchetti E, Ghezzi D, Benfenati F, Lanzani G, Antognazza MR (2015) Photothermal cellular stimulation in functional bio-polymer interfaces. Sci. Rep. 5: 8911.

Caiazzo M, Giannelli S, Valente P, Lignani G, Carissimo A, Sessa A, Colasante  G, Bartolomeo R, Massimino L, Ferroni S, Settembre C, Benfenati F, Broccoli V (2015) Direct conversion of fibroblasts into functional astrocytes by defined transcription factors. Stem Cell Rep. 4: 25-36.

Gill I, Droubi S, Giovedi S, Fedder KN, Bury LA, Bosco F, Sceniak MP, Benfenati F, Sabo SL (2015) Presynaptic NMDA receptors - dynamics and distribution in developing axons in vitro and in vivo. J. Cell Sci. 128: 768-780.

Milanese M, Bonifacino T, Fedele E, Rebosio C, Cattaneo L, Benfenati F, Usai C, Bonanno G (2015) Exocytosis regulates trafficking of GABA and glycine heterotransporters in spinal cord glutamatergic synapses: a mechanism for the excessive heterotransporter-induced release of glutamate in experimental amyotrophic lateral sclerosis. Neurobiol. Dis. 74: 314-324.

Orlando M, Lignani G, Maragliano L, Fassio A, Onofri F, Baldelli P, Giovedí S, Benfenati F (2014) Functional role of ATP binding to synapsin I in synaptic vesicle trafficking and release dynamics. J. Neurosci. 34:14752-14768. 

Cesca F, Limongi T, Accardo A, Rocchi A, Orlando M, Shalabaeva V, Di Fabrizio E*, Benfenati F* (2014) Fabrication of biocompatible free-standing nanopatterned films for primary neuronal cultures. RSC Adv. 4: 45696. * last co-authors

Giovedí S, Corradi A, Fassio A, Benfenati F (2014) Involvement of synaptic genes in the pathogenesis of autism spectrum disorders: the case of synapsins. Front. Pediatr. 2: 94. 

Fossati SM, Candiani S, Nödl MT, Maragliano L, Pennuto M, Domingues P, Benfenati F, Pestarino M, Zullo L (2015) Identification and expression of acetylcholinesterase in Octopus vulgaris arm development and regeneration: a conserved role for ACHE? Mol. Neurobiol. 252: 45-56.

Medrihan L, Ferrea E, Greco B, Baldelli P, Benfenati F (2015) Asynchronous GABA release is a key determinant of tonic inhibition and controls neuronal excitability: a study in the Synapsin II-/- mouse. Cereb. Cortex 25: 3356-3368.

Dell'Anno MT, Caiazzo M, Leo D, Dvoretskova E, Medrihan L, Colasante G, Giannelli S, Theka I, Russo G, Mus L, Pezzoli G, Gainetdinov RR, Benfenati F, Taverna S, Dityatev A, Broccoli V (2014) Remote control of induced dopaminergic neurons in parkinsonian rats. J. Clin. Invest. 124: 3215-3229.

Petrini EM, Ravasenga T, Hausrat TJ, Iurilli G, Olcese U, Racine V, Sibarita JB, Jacob TC, Moss SJ, Benfenati F, Medini P, Kneussel M, Barberis A (2014) Synaptic recruitment of gephyrin regulates surface GABAA receptor dynamics for the expression of inhibitory LTP. Nat. Commun. 5: 3921.

Verstegen AM, Tagliatti E, Lignani G, Marte A, Stolero T, Atias M, Corradi A, Valtorta F, Gitler D, Onofri F, Fassio A, Benfenati F (2014) Phosphorylation of synapsin I by cyclin-dependent kinase-5 sets the ratio between the resting and recycling pools of synaptic vesicles at hippocampal synapses. J. Neurosci. 34: 7266-7280.

Falace A, Buhler E, Fadda M, Watrin F, Lippiello P, Pallesi-Pocachard E, Baldelli P, Benfenati F, Zara F, Represa A, Fassio A, Cardoso C (2014) TBC1D24 regulates neuronal migration and maturation through modulation of the ARF6-dependent pathway. Proc. Natl. Acad. Sci. USA 111: 2337-2342.

Corradi A, Fadda M, Piton A, Patry L, Marte A, Rossi P, Cadieux-Dion M, Gauthier J, Lapointe L, Mottron L, Valtorta F, Rouleau GA, Fassio A, Benfenati F*§, Cossette P* (2014) SYN2 is an autism predisposing gene: loss-of-function mutations alter synaptic vesicle cycling and axon outgrowth. Hum Mol. Genet. 23: 90-103. * last co-authors;  §corresponder.

Pozzi D, Lignani G, Ferrea E, Contestabile A, Paonessa F, D’Alessandro R, Lippiello P, Boido D, Fassio A, Meldolesi J, Valtorta F, Benfenati F, Baldelli P (2013) REST/NRSF-mediated intrinsic homeostasis protects neuronal networks from hyperexcitability. EMBO J. 32: 2994-3007.

Ghezzi D, Antognazza MR, Maccarone R, Bellani S, Lanzarini E, Martino N, Mete M, Pertile G, Bisti S, Lanzani G, Benfenati F (2013) A polymer optoelectronic interface restores light sensitivity in blind rat retinas. Nature Photonics 7: 407-412. Issue Cover.

Medrihan L, Cesca F, Raimondi A, Lignani G, Baldelli P, Benfenati F (2013) Synapsin II desynchronizes neurotransmitter release at inhibitory synapses by a functional interaction with presynaptic Ca2+ channels. Nature Comm. 4:1512.

Lignani G, Ferrea E, Difato F, Amarù J, Ferroni E, Lugarà E, Espinoza S, Gainetdinov RR, Baldelli P, Benfenati F (2013) Long-term optical stimulation of channelrhodopsin-expressing neurons to study network plasticity. Front Mol Neurosci. 6: 22.

Paonessa F, Latifi S, Scarongella H, Cesca F*, Benfenati F* (2013) Specificity protein 1 (Sp1)-dependent activation of the synapsin I gene (SYN1) is modulated by RE1-silencing transcription factor (REST) and 5'-cytosine-phosphoguanine (CpG) methylation. J Biol Chem. 288: 3227-3239. * last co-authors

Lignani G, Raimondi A, Ferrea E, Rocchi A, Paonessa F, Cesca F, Orlando M, Tkatch T, Valtorta F, Cossette P, Baldelli P, Benfenati F (2013) Epileptogenic Q555X SYN1 mutant triggers imbalances in release dynamics and short-term plasticity. Hum Mol Genet. 22: 2186-2199.

Toader O, Forte N, Orlando M, Ferrea E, Raimondi A, Baldelli P, Benfenati F, Medrihan L (2013) Dentate gyrus network dysfunctions precede the symptomatic phase in a genetic mouse model of seizures. Front. Cell Neurosci. 7: 138.

Limongi T, Cesca F, Gentile F, Marotta R, Ruffilli R, Barberis A, Dal Maschio M, Petrini EM, Santoriello S, Benfenati F*, Di Fabrizio E* (2013) Nanostructured superhydrophobic substrates trigger the development of 3D neuronal networks. Small 9: 402-412. * last co-authors

Contestabile A, Greco B, Ghezzi D, Tucci V, Benfenati F, Gasparini L (2013) Lithium rescues synaptic plasticity and memory in Down syndrome mice. J. Clin. Invest. 123: 348-361.

Greco B, Managò F, Tucci V, Kao HT, Valtorta F, Benfenati F (2013) Autism-related behavioral abnormalities in synapsin knockout mice. Behav. Brain Res. 251: 65-74.

Milh M, Falace A, Villeneuve N, Vanni N, Cacciagli P, Assereto S, Nabbout R, Benfenati F, Zara F, Chabrol B, Villard L, Fassio A (2013) Novel compound heterozygous mutations in TBC1D24 cause familial malignant migrating partial seizures of infancy. Hum. Mutat. 34: 869-872.

Bragina L, Fattorini G, Giovedì S, Bosco F, Benfenati F, Conti F (2013) Heterogeneity of presynaptic proteins: do not forget isoforms. Front. Cell Neurosci. 7: 8.

Lignani G, Ferrea E, Difato F, Amarù J, Ferroni E, Lugarà E, Espinoza S, Gainetdinov RR, Baldelli P, Benfenati F (2013) Long-term optical stimulation of channelrhodopsin-expressing neurons to study network plasticity. Front. Mol. Neurosci. 6: 22.

De Faveri S, Maggiolini E, Miele E, De Angelis F, Cesca F, Benfenati F*, Fadiga L* (2013) Bio-inspired hybrid microelectrodes: a hybrid solution to improve long-term performance of chronic intracortical implants. Front Neuroeng. 7: 7. * last co-authors

Giannandrea M, Guarnieri FC, Gehring NH, Monzani E, Benfenati F, Kulozik AE, Valtorta F (2013) Nonsense-mediated mRNA decay and loss-of-function of the protein underlie the X-linked epilepsy associated with the W356× mutation in synapsin I. PLoS One 8: e67724.

Farisello P, Boido D, Nieus T, Medrihan L, Cesca F, Valtorta F, Baldelli P, Benfenati F (2013) Synaptic and extrasynaptic origin of the excitation/inhibition imbalance in the hippocampus of Synapsin I/II/III knockout mice. Cereb. Cortex 23: 581-593.

Gelsomino G, Menna E, Antonucci F, Rodighiero S, Riganti L, Mulle C, Benfenati F, Valtorta F, Verderio C, Matteoli M (2013) Kainate induces mobilization of  synaptic vesicles at the growth cone through the activation of protein kinase A. Cereb. Cortex 23: 531-541.

Cambiaghi M, Cursi M, Monzani E, Benfenati F, Comi G, Minicucci F, Valtorta F, Leocani L (2013) Temporal evolution of neurophysiological and behavioral features of synapsin I/II/III triple knock-out mice. Epilepsy Res. 103: 153-160.

Nazzaro C, Greco B, Cerovic M, Baxter P, Rubino T, Trusel M, Tkatch T, Benfenati F, Pedarzani P, Tonini R (2012). In vivo modulation of SK channels rescues striatal synaptic plasticity and habitual control in cannabinoid dependence. Nature Neurosci. 15: 284-293.

Iurilli G, Ghezzi D, Olcese U, Lassi G, Nazzaro C, Tonini R, Tucci V, Benfenati F, Medini P (2012) Sound-driven synaptic inhibition in primary visual cortex. Neuron 73: 814-828.

Ferrea E, Maccione A, Medrihan L, Nieus T, Ghezzi D, Baldelli P, Benfenati F, Berdondini L (2012) Large-scale, high-resolution electrophysiological imaging of field potentials in brain slices with microelectronic multielectrode arrays. Front. Neural Circuits 6: 80.

Zullo L, Chiappalone M, Martinoia S, Benfenati F (2012) A "spike-based" grammar underlies directional modification in network connectivity: effect on bursting activity and implications for bio-hybrids systems. PLoS One 7: e49299.

Fornasiero EF, Raimondi A, Guarnieri FC, Orlando M, Fesce R, Benfenati F, Valtorta F (2012) Synapsins contribute to the dynamic spatial organization of synaptic  vesicles in an activity-dependent manner. J. Neurosci. 32: 12214-12227.

Oulès B, Del Prete D, Greco B, Zhang X, Lauritzen I, Sevalle J, Moreno S, Paterlini-Bréchot P, Trebak M, Checler F, Benfenati F, Chami M (2012) Ryanodine receptor blockade reduces amyloid-β load and memory impairments in Tg2576 mouse model of Alzheimer disease. J. Neurosci. 32: 11820-11834.

Valente P, Casagrande S, Nieus T, Verstegen AM, Valtorta F, Benfenati F, Baldelli P (2012) Site-specific synapsin I phosphorylation participates in the expression of post-tetanic potentiation and its enhancement by BDNF. J. Neurosci. 32: 5868-5879.

Neubrand VE, Cesca F, Benfenati F, Schiavo G (2012). Kidins220/ARMS as a functional mediator of multiple receptor signalling pathways. J. Cell Sci. 125: 1845-1854.

Marconi E, Nieus T, Maccione A, Valente P, Simi A, Messa M, Dante S, Baldelli P, Berdondini L, Benfenati F (2012). Emergent functional properties of neuronal networks with controlled topology. PLoS One 7: e34648.

Succol F, Fiumelli H, Benfenati F, Cancedda L, Barberis A (2012) Intracellular chloride concentration influences the GABAA receptor subunit composition. Nat Commun 3: 738.

Ghezzi D, Antognazza MR, Dal Maschio M, Lanzarini E, Benfenati F*, Lanzani G* (2011) A hybrid bioorganic interface for neuronal photoactivation. Nature Comm. 2:166. News&Views in Nature Photonics 5: 138, 2011. * last co-authors

Cesca F, Yabe A, Spencer-Dene B, Scholz-Starke J, Medrihan L, Maden CH, Gerhardt H, Orriss IR, Baldelli P, Al-Qatari M, Koltzenburg M, Adams RH, Benfenati F*, Schiavo G* (2011) Kidins220/ARMS mediates the integration of the neurotrophin and VEGF pathways in the vascular and nervous systems. Cell Death Differ. (Nature Publ. Group) 19:194-208. *FB: co-last author

Blau A, Murr A, Wolff S, Sernagor E, Medini P, Iurilli G, Ziegler C, Benfenati F (2011) Flexible, all-polymer microelectrode arrays for the capture of cardiac and neuronal signals. Biomaterials 32: 1778-1786.

Fassio A, Patry L, Congia S, Onofri F, Piton A, Gauthier J, Pozzi D, Messa M, Defranchi E, Fadda M, Corradi A, Baldelli P, Lapointe L, St-Onge J, Meloche C, Mottron L, Valtorta F, Khoa Nguyen D, Rouleau GA, Benfenati F*, Cossette P* (2011) SYN1 loss-of-function mutations in autism and partial epilepsy cause impaired synaptic function. Hum. Mol. Genet. 20: 2297-2307. * last co-authors

Wang S, Cesca F, Loers G, Schweizer M, Buck F, Benfenati F, Schachner M, Kleene R (2011) Synapsin I is an oligomannose-carrying glycoprotein, acts as an oligomannose-binding lectin, and promotes neurite outgrowth and neuronal survival when released via glia-derived exosomes. J. Neurosci. 31: 7275-7290.

Valtorta F, Pozzi D, Benfenati F, Fornasiero EF (2011) The synapsins: multitask modulators of neuronal development. Semin. Cell Dev. Biol. 22: 378-386.

Fassio A, Raimondi A, Lignani G, Benfenati F, Baldelli P (2011) Synapsins: from synapse to network hyperexcitability and epilepsy. Semin. Cell Dev. Biol. 22: 408-415.

Perlini LE, Botti F, Fornasiero EF, Giannandrea M, Bonanomi D, Amendola M, Naldini L, Benfenati F, Valtorta F (2011) Effects of phosphorylation and neuronal activity on the control of synapse formation by synapsin I. J. Cell Sci. 124: 3643-3653.

Krabben L, Fassio A, Bhatia VK, Pechstein A, Onofri F, Fadda M, Messa M, Rao Y, Shupliakov O, Stamou D, Benfenati F, Haucke V (2011) Synapsin I senses membrane curvature by an amphipathic lipid packing sensor motif. J. Neurosci. 31: 18149-18154.

Other selected publications:

- Benfenati F., Bähler M., Brunner J., Greengard P. Electrostatic and hydrophobic interactions of synapsin I with phospholipid vesicles. J. Cell Biol. 108: 1851-1862, 1989.

- Benfenati F., Bähler M., Jahn R., Greengard P. Interaction of synapsin I with small synaptic vesicles: distinct sites in synapsin I bind to vesicle phospholipids and vesicle proteins.  J. Cell Biol. 108: 1863-1872, 1989.

- De Camilli P., Benfenati F., Valtorta F., Greengard P. The synapsins. Annu. Rev. Cell Biol. 6: 433-460, 1990.

- Benfenati F., Valtorta F., Greengard P. Computer modeling of synapsin I binding to synaptic vesicles and F-actin: implications for the regulation of neurotransmitter release. Proc. Natl. Acad. Sci. USA 88: 575-579, 1991.

- Benfenati F., Valtorta F., Chieregatti E., Greengard P. Interaction of free and synaptic vesicle-bound synapsin I with F-actin. Neuron, 8: 377-386, 1992.

- Benfenati F., Valtorta F., Rubenstein J.L., Gorelick F., Greengard P., Czernik A.J. Synaptic vesicle-associated Ca2+/calmodulin-dependent protein kinase II is a binding protein for synapsin I. Nature 359: 417-420, 1992.

- Schiavo G., Benfenati F., Poulain B., Rossetto O., Polverino de Laurato P., DasGupta B. R., Montecucco C. Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin-2. Nature, 359: 832-835, 1992.

- Greengard P., Valtorta F., Czernik A. J., Benfenati F. Synaptic vesicle phosphoproteins and regulation of synaptic function. Science, 259: 780-785, 1993.

- Benfenati F., Valtorta F., Rossi M.C., Onofri F., Sihra T., Greengard P. Interactions of synapsin I with phospholipids: possible role in synaptic vesicle clustering and in the maintenance of bilayer structures. J. Cell Biol., 123: 1845-1855, 1993.

- Jovanovic J., Benfenati F., Siow Y.L., Sihra T.S., Sanghera J.S., Pelech S.L., Greengard P., Czernik A.J. Neurotrophins stimulate phosphorylation of synapsin I by MAP kinase and regulate synapsin I-actin interactions. Proc. Natl. Acad. Sci. USA, 93: 3679-3683, 1996.

- Onofri F., Giovedì S., Vaccaro P., Czernik A.J., Valtorta F., De Camilli P., Greengard P., Benfenati F. Synapsin I interacts with c-Src and stimulates its tyrosine kinase activity. Proc. Natl. Acad. Sci. USA 94: 12168-12173, 1997.

- Kao H-T., Porton B., Czernik A.J., Feng J., Yiu G., Haring M., Benfenati F., Greengard P. A third member of the synapsin gene family. Proc. Natl. Acad. Sci. USA 95: 4667-4672, 1998.

- Jaffrey S.R., Benfenati F., Snowman A.M., Czernik A.J., Snyder S.H. Neuronal nitric oxide synthase localization mediated by a ternary complex with synapsin and CAPON. Proc. Natl. Acad. Sci. USA, 99: 3199-3204, 2002.

- Schenk U., Verderio C., Benfenati F., Matteoli M. Regulated delivery of AMPA receptor subunits to the presynaptic membrane. EMBO J., 22: 558-568, 2003.

- Guo J., Wenk M.R., Pellegrini L., Onofri F., Benfenati F., De Camilli P. Phosphatidylinositol 4-kinase type IIa is responsible for the phosphatidylinositol 4-kinase activity associated with synaptic vesicles. Proc.Natl.Acad.Sci.USA, 100, 3995-4000, 2003.

- Hilfiker S., Benfenati F., Doussau F., Nairn A.C., Czernik A.J., Augustine G.J., Greengard P. Structural domains involved in the regulation of transmitter release by synapsins.  J. Neurosci. 25: 2658 - 2669, 2005.

- Bonanomi D., Menegon A., Miccio A., Ferrari G., Corradi A., Kao H-T., Benfenati F., Valtorta F. Phosphorylation of Synapsin I by cyclic AMP-dependent protein kinase controls synaptic vesicle dynamics in developing neurons. J. Neurosci., 25: 7299-7308, 2005.

- Menegon A., Bonanomi D., Albertinazzi C., Lotti F., Ferrari G., Kao H-T., Benfenati F., Baldelli P., Valtorta F. Protein kinase A-mediated synapsin I phosphorylation is a central modulator of Ca2+-dependent synaptic activity. J. Neurosci., 26: 11670-11681, 2006

- Fassio A., Merlo D., Mapelli J., Menegon A., Corradi A., Mete M., Zappettini S., Bonanno G., Valtorta F., D'Angelo E., Benfenati F. The synapsin domain E accelerates the exo-endocytotic cycle of synaptic vesicles in cerebellar Purkinje cells. J. Cell Sci., 119: 4257-4268, 2006.

- Baldelli P., Fassio A., Valtorta F., Benfenati F. Lack of synapsin I reduces the readily releasable pool of synaptic vesicles at central inhibitory synapses. J. Neurosci.  27:13520-13531, 2007.

- Corradi A., Zanardi A., Giacomini C., Onofri F., Valtorta F., Zoli M., Benfenati F. Synapsin I and synapsin II null mice display an increased age-dependent cognitive impairment. J. Cell Sci., 121: 3042-3051, 2008.

- Chiappalone M., Casagrande S. Tedesco M., Valtorta F., Baldelli P., Martinoia S., Benfenati F. Opposite changes in glutamatergic and GABAergic transmission underlie the diffuse hyperexcitability of Synapsin I-deficient cortical networks. Cerebral Cortex, 19: 1422-1439, 2009.

- Cesca F, Baldelli P, Valtorta F, Benfenati F (2010) The Synapsins: Key Actors of Synapse Function and Plasticity. Prog. Neurobiol., 91:313-348.

 

Patent Applications:

- PCT/IB2009/050751. “POLY-MEA: Microelectrode array based on optically transparent conductive polymer materials and a method of fabrication thereof” Inventors: A Blau, F Benfenati.

- PCT/IB2012/057280. “Sistema integrato di microscopia a forza ottica e a forza atomica“ Inventors: F

Difato, B Torre, A Diaspro, F Benfenati, R Cingolani.

- ITTO2012A000331. “Novel methods of 3D neuronal cell culture using superhydrophobic substrates” Inventors: E Di Fabrizio, T Limongi, F Gentile, R Marotta, F Benfenati, F Cesca.

- PCT/IB2012/052327(E0085129); Publication date 15/5/2012: “Catto-electrode Electroporation Device” Inventors: L Cancedda, GM Ratto, F Benfenati.

- US 13/351046 (publication date 16/1/2012). “A hybrid bioorganic interface for neuronal photoactivation” Inventors: MR Antognazza, D Ghezzi, M Dal Maschio, E Lanzarini, G Lanzani, F Benfenati.

- TO2013A000665. “Organic device for photoinhibition of excitable cells" Inventors: MR Antognazza, D Ghezzi, G Lanzani, G Pertile, M Mete, F Benfenati.

Awards

1979: "Thesis Prize" and thesis publication by the University of Bologna

1980: Prize for Neurobiology, Accademia Nazionale dei Lincei,

1986-1987: Fogarty International Center Fellowship from the US Public Health Service

1988: “Italian Society for Neuroscience” Prize for young neuroscientists

1997: Fullbright Advanced Research and University Lecturing Award

2003: Research Award, Foundation of the Fisher Center for Alzheimer’s Disease, USA

2012: Foreign Scientist Award, The Michael Stern Foundation for Parkinson's Disease, USA

2012: Smart Cup and National Innovation Prize (PNI) for Life Sciences for the project "ON-IRIS, the photovoltaic artificial retina"

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I numeri di IIT

L’Istituto Italiano di Tecnologia (IIT) è una fondazione di diritto privato - cfr. determinazione Corte dei Conti 23/2015 “IIT è una fondazione da inquadrare fra gli organismi di diritto pubblico con la scelta di un modello di organizzazione di diritto privato per rispondere all’esigenza di assicurare procedure più snelle nella selezione non solo nell’ambito nazionale dei collaboratori, scienziati e ricercatori ”.

IIT è sotto la vigilanza del Ministero dell'Istruzione, dell'Università e della Ricerca e del Ministero dell'Economia e delle Finanze ed è stato istituito con la Legge 326/2003. La Fondazione ha l'obiettivo di promuovere l'eccellenza nella ricerca di base e in quella applicata e di favorire lo sviluppo del sistema economico nazionale. La costruzione dei laboratori iniziata nel 2006 si è conclusa nel 2009.

Lo staff complessivo di IIT conta circa 1440 persone. L’area scientifica è rappresentata da circa l’85% del personale. Il 45% dei ricercatori proviene dall’estero: di questi, il 29% è costituito da stranieri provenienti da oltre 50 Paesi e il 16% da italiani rientrati. Oggi il personale scientifico è composto da circa 60 principal investigators, circa 110 ricercatori e tecnologi di staff, circa 350 post doc, circa 500 studenti di dottorato e borsisti, circa 130 tecnici. Oltre 330 posti su 1400 creati su fondi esterni. Età media 34 anni. 41% donne / 59 % uomini.

Nel 2015 IIT ha ricevuto finanziamenti pubblici per circa 96 milioni di euro (80% del budget), conseguendo fondi esterni per 22 milioni di euro (20% budget) provenienti da 18 progetti europei17 finanziamenti da istituzioni nazionali e internazionali, circa 60 progetti industriali

La produzione di IIT ad oggi vanta circa 6990 pubblicazioni, oltre 130 finanziamenti Europei e 11 ERC, più di 350 domande di brevetto attive, oltre 12 start up costituite e altrettante in fase di lancio. Dal 2009 l’attività scientifica è stata ulteriormente rafforzata con la creazione di dieci centri di ricerca nel territorio nazionale (a Torino, Milano, Trento, Parma, Roma, Pisa, Napoli, Lecce, Ferrara) e internazionale (MIT ed Harvard negli USA) che, unitamente al Laboratorio Centrale di Genova, sviluppano i programmi di ricerca del piano scientifico 2015-2017.

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IIT: the numbers

Istituto Italiano di Tecnologia (IIT) is a public research institute that adopts the organizational model of a private law foundation. IIT is overseen by Ministero dell'Istruzione, dell'Università e della Ricerca and Ministero dell'Economia e delle Finanze (the Italian Ministries of Education, Economy and Finance).  The Institute was set up according to Italian law 326/2003 with the objective of promoting excellence in basic and applied research andfostering Italy’s economic development. Construction of the Laboratories started in 2006 and finished in 2009.

IIT has an overall staff of about 1,440 people. The scientific staff covers about 85% of the total. Out of 45% of researchers coming from abroad 29% are foreigners coming from more than 50 countries and 16% are returned Italians. The scientific staff currently consists of approximately 60 Principal Investigators110 researchers and technologists350 post-docs and 500 PhD students and grant holders and 130 technicians. External funding has allowed the creation of more than 330 positions . The average age is 34 and the gender balance proportion  is 41% female against 59% male.

In 2015 IIT received 96 million euros in public funding (accounting for 80% of its budget) and obtained 22 million euros in external funding (accounting for 20% of its budget). External funding comes from 18 European Projects, other 17 national and international competitive projects and approximately 60 industrial projects.

So far IIT accounts for: about 6990 publications, more than 130 European grants and 11 ERC grants, more than 350 patents or patent applications12 up start-ups and as many  which are about to be launched. The Institute’s scientific activity has been further strengthened since 2009 with the establishment of 11 research nodes throughout Italy (Torino, Milano, Trento, Parma, Roma, Pisa, Napoli, Lecce, Ferrara) and abroad (MIT and Harvard University, USA), which, along with the Genoa-based Central Lab, implement the research programs included in the 2015-2017 Strategic Plan.

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