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Dott.ssa Benedetta Elena Fornasari

Contatti

Tutore

Prof. Giovanna Gambarotta

Curriculum vitae

Curriculum Vitae

Tesi di dottorato

Neuregulin1 expression following peripheral nerve injury and new tools to improve nerve regeneration

 

 

 

Attività di ricerca

 

Neuregulin1 expression following peripheral nerve injury and new tools to improve nerve regeneration

Neuregulin1 (NRG1) is a growth factor belonging to the EGF-family, and it is a ligand for tyrosine-kinase receptors of the ErbB family. NRG1 has different isoforms and it is involved in many biological processes. In the central nervous system it plays a role in neuronal migration during development, in the peripheral nervous system it is involved in  nerve development and its regeneration after injury. In the peripheral nervous system we showed that, immediately after a nerve injury, the expression of soluble NRG1 and its isoforms α, β, a, and b, is highly up-regulated. Injured nerves without a proper repair can degenerate, and in the distal stump of these nerves the expression of soluble NRG1 is strongly down-regulated and Schwann cells undergo atrophy, suggesting that NRG1 lacking might explain Schwann cell impairment. Indeed, when the repair time is delayed, the outcome is worse than after an immediate repair. We hypothesized that the supply of exogenous NRG1 might improve nerve regeneration when NRG1 is not sufficiently provided by endogenous Schwann cells, like in hollow conduits or in delayed repair. To this aim, we performed preliminary assays introducing inside a hollow chitosan tube, used to bridge proximal and distal stumps of an injured nerve, skeletal muscle fibres, which express and release soluble NRG1, showing that for immediately repaired short gaps its use is effective. These data suggest that the introduction of muscle fibres releasing soluble NRG1 might be a promising strategy to obtain a better outcome also when the repair is delayed in time. As an alternative, we developed biomaterials that might be functionalized to release soluble NRG1: we demonstrated, in vitro, that random and aligned gelatin and chitosan fibres, with their morphology, enhance Schwann cell proliferation, adhesion and migration, characteristics making them a suitable internal filler for nerve conduits. We also demonstrated that soluble NRG1 isoforms are chronically over-expressed in the nerves of the most common inherited peripheral neuropathy (Charcot-Marie-Tooth1A), that is characterized by demyelination. Finally, in the central nervous system, we showed that NRG1α and β are expressed in the cortex and we demonstrated in vitro that both isoforms can stimulate the migration of neuronal progenitors.

 

 

 

-Data Report XXVIII ciclo, 14:00-16:00, 25-26 February 2014

-"Essere giovani protagonisti in H2020: il CV e opportunità di finanziamento attraverso la mobilità internazionale" Claudia Barale, Università di Torino.

 - Corso di scrittura: "How to write a scientific paper"- Sonal Jhaveri, Department of Brain and Cognitive Sciences, Massachussets Institute of Technology, Cambridge, MA. 9:00-12:00, 10-12 July 2014, Aula A di Anatomia Umana, corso Massimo d'Azeglio, 52. 

- Neural Development and Neurodevelopmental Disorders (NensCourse Torino) 22-26 settembre, PhD course

-Allen Institute for Brain Science Informational Overview and Training Workshop, 3 Oct 2014, Turin 

-Data Report XXIX cycle, 14:00-16:00, 24-25 February 2015

- Corso di Statistica, 15,23 june, 13 july, MBC, Torino, Italy

-Neurobiology I. Cellular and molecular organization of the nervous system, 14:00-18:00 22 June-21 July 2015

-D-day 2015, Turin (Aula Magna Rettorato), 16th September 2015

- International PhD Course on The Aging Brain: Cellular Mechanisms Interfacing Human Pathology -  Turin, September 28- October 2, 2015

-English Course, 14:00-16:00 (25 lessons), from November 16, 2015

-Biostatistica per il Dottorato in neuroscienze - Turin, May 2- July , 2016

-D-day 2016, Turin (MBC, via Nizza 52), 15th September 2016

-Giornata dedicata alla valorizzazione delle competenze dei dottori di ricerca e al postdoc, ,Turin (Aula Magna Cavallerizza Reale, via Verdi 9), October 4, 2016

-Workshop: "Essential Public Speking Skills for postdocs", Turin (Sala Multifunzionale, Cavallerizza Reale, via Verdi 9), October 4, 2016

-Seconda edizione del Premio Aldo Fasolo, Accademia delle Scienze (Torino), December 16,  2016 

-Course: "The Brain in Extreme Environments", March 6 and April 10-11, 2017

-D-day 2017, Turin (MBC, via Nizza 52), 17th September 2017

 

 

1) G. Ronchi*, B.E.Fornasari*, A. Crosio, C.A. Budau, P. Tos, I. Perroteau, B. Battiston, S. Geuna, S. Raimondo, G. Gambarotta. Chitosan Tubes Enriched with Fresh Skeletal Muscle Fibers for Primary Nerve Repair. BioMed Research International. 2018 June 13. 2018:9175248. doi: 10.1155/2018/9175248. 

2) M. El Soury, B.E. Fornasari, M. Morano, E. Grazio, G. Ronchi, D. Incarnato, M. Giacobini, S. Geuna, P. Provero, G. Gambarotta. Soluble Neuregulin1 down-regulates myelination genes in Schwann cells. Frontiers in Molecular Neuroscience. 2018 May 14. 14;11:157. doi: 10.3389/fnmol.2018.00157. 

3) S. Gnavi, M. Morano, B.E. Fornasari, C. Riccobono, C. Tonda-Turo, M. Zanetti, G Ciardelli, G. Gambarotta, I. Perroteau, S. Geuna, S. Raimondo. Combined influence of gelatin fibre topography and growth factors on cultured dorsal root ganglia neurons. Anatomical Record (Hoboken). 2018 Apr 30. doi: 10.1002/ar.23846. Corresponding author

4) M. Morano, G. Ronchi, V. Nicolò, B.E. Fornasari, A Crosio, I. Perroteau, S. Geuna, G. Gambarotta, S. Raimondo, Modulation of the Neuregulin 1/ErbB system after skeletal muscle denervation and reinnervation. Scientific Reports. 2018 Mar 22;8(1):5047. doi: 10.1038/s41598-018-23454-8. 

5) B.E. Fornasari, G. Ronchi, D. Pascal, D. Visigalli, G. Capodivento, L. Nobbio, I. Perroteau, A. Schenone, S. Geuna, G. Gambarotta, Soluble Neuregulin1 is strongly up-regulated in the rat model of Charcot-Marie-Tooth 1A disease, Experimental Biology and Medicine. 2018 Feb; 243(4):370-374. doi: 10.1177/1535370218754492. 

6) G. Ronchi, M. Cillino, G. Gambarotta, B.E. Fornasari, S. Raimondo, P. Pugliese, P. Tos, A. Cordova, F. Moschella, S. Geuna,  Irreversible changes occurring in long-term denervated Schwann cells affect delayed nerve repair, Journal of Neurosurgery. 2017 Jan 6:1-14. doi: 10.3171/2016.9.JNS16140.

7) B.E. Fornasari, M. El Soury, S. De Marchis, I. Perroteau, S. Geuna, G. Gambarotta, Neuregulin1 alpha activates migration of neuronal progenitors expressing ErbB4, Molecular and Cellular Neuroscience. 77(2016) 87-94. doi:10.1016/j.mcn.2016.10.008.

8) S. Gnavi, B.E. Fornasari,  C. Tonda-Turo, R. Laurano, M. Zanetti, G. Ciardelli, S. Geuna, In vitro evaluation of gelatin and chitosan electrospun fibers as artificial guide in peripheral nerve repair: a comparative study, Journal of Tissue Engineering and Regenerative Medicine.  2016 Nov 12. doi: 10.1002/term.2351. 

9) S. Gnavi, B.E. Fornasari, C. Tonda-Turo, R. Laurano, M. Zanetti, G. Ciardelli, S. Geuna, The effect of electrospun fibre alignment on Schwann cell and axonal behaviour and organization, International Journal of Molecular Sciences. 2015 Jun 8;16(6):12925-42. doi: 10.3390/ijms160612925. 

10) G. Ronchi, K. Haastert-Talini, B.E. Fornasari, I. Perroteau, S. Geuna, G. Gambarotta, The Neuregulin 1/ErbB system is selectively regulated during nerve degeneration and regeneration, European Journal of Neuroscience. 2016 Feb;43(3):351-64. doi: 10.1111/ejn.12974. 

11) S. Gnavi, B.E. Fornasari, C. Tonda-Turo, G. Ciardelli, M. Zanetti, S. Geuna, I. Perroteau, The influence of electrospun fibre size on Schwann cell behaviour and axonal outgrowth, Materials Science and Engineering C. 2015 Mar;48:620-31. doi: 10.1016/j.msec.2014.12.055. doi: 10.3390/ijms160612925. 

 

1)       B.E. Fornasari, C.Tonda-Turo, E. Cipriani, M. Zanetti, G. Ciardelli, I. Perroteau, S. Geuna and S. Gnavi - The influence of fibre diameter on electrospun substrates on Schwann cell behaviour and axonal outgrowth for nerve tissue engineering, 2nd International Symposium on Peripheral Nerve Regeneration, Turin, January 23-25, 2014.

2)       B.E. Fornasari, C.Tonda-Turo, E. Cipriani, M. Zanetti, G. Ciardelli, I. Perroteau, S. Geuna, S. Gnavi - Influence of gelatine fibre diameter on Schwann cell behaviour and axonal outgrowth, Fens Forum, Milan (Italy), July 5-9, 2014.

3)       B.E. Fornasari, C.Tonda-Turo, E. Cipriani, M. Zanetti, G. Ciardelli, I. Perroteau, S. Geuna and S. Gnavi - Gelatin fibre diameter influences  Schwann cell behaviour and axonal outgrowth,  XXIV Convegno Nazionale Gruppo Italiano per lo Studio della Neuromorfologia, Bologna (Italy), November 28-29, 2014. (ORAL SPEECH)

4)        S. Gnavi, B.E. Fornasari, C. Tonda-Turo, R. Laurano, M. Zanetti, G. Ciardelli, S.Geuna - The influence of electrospun fibre alignment on Schwann cell behaviour and axonal outgrowth, Quinta Riunione Annuale dell'Associazione italiana per lo studio del Sistema Nervoso Periferico (ASNP). Turin (Italy), April 9-11, 2015.

5)       G. Ronchi, K. Haastert-Talini, B.E. Fornasari , N. Viano,  I. Perroteau, S. Geuna, G. Gambarotta -  Selective regulation of the Neuregulin1/ErbB system after peripheral nerve injury, 2015 PNS Biennial Meeting, Quebec City (Canada), June 28-July 2, 2015

6)       G. Ronchi, M. Cillino, B.E. Fornasari, G. Gambarotta, L. Montafia, S. Raimondo, P.Tos, F. Moschella, S. Geuna - Are the changes occuring in the nerve distal to chronic transection reversibile?, 3nd International Symposium on Peripheral Nerve Regeneration, Hannover (Germany), September 23-25, 2015.

7)       S. Gnavi, C. Tonda Turo, M. Morano, B.E. Fornasari, C. Riccobono, M. Zanetti, G. Ciardelli, I. Perroteau and S. Geuna - Electrospun gelatin fibers features modulate Schwann cells and DRG neuron behaviour, 3nd International Symposium on Peripheral Nerve Regeneration, Hannover (Germany), September 23-25, 2015.

8)       G. Gambarotta, G. Ronchi, K. Haastert-Talini, B.E. Fornasari, A. Crosio, I. Perroteau, S. Geuna - The regulation of the neuregulin1/ErbB system in the degenerating and regenerating nerve, 3nd International Symposium on Peripheral Nerve Regeneration, Hannover (Germany), September 23-25, 2015.

9)       G. Gambarotta, G. Ronchi, K. Haastert-Talini, B. E. Fornasari, A. Crosio, I. Perroteau, S. Geuna - Neuregulin1/ErbB expression regulation in the injured rat peripheral nerve during degeneration and regeneration, Neuroscience 2015, Chicago, Illinois (USA), October 17-21, 2015

10)     B.E. Fornasari, G. Ronchi, A. Crosio, P. Pugliese, L. Montafia, I. Perroteau, S. Geuna,G. Gambarotta - Empty chitosan tube as a model to study peripheral nerve regeneration in an isolated system, Congresso Nazionale della Società  Italiana di Microchirurgia (SIM), Turin (Italy), November 26-28, 2015. (ORAL SPEECH)

11)    B.E. Fornasari, S. Gnavi, C. Tonda-Turo, M. Zanetti, G. Ciardelli, S. Geuna - In vitro evaluation of gelatin and chitosan electrospun nanofibers as artificial guide in peripheral nerve repair, European Chapter Meeting of the Tissue Engineering and Regenerative Medicine International Society (TERMIS), Uppsala (Sweden), June 28- July 1, 2016. 

12)   G. Gambarotta, B.E. Fornasari, G. Ronchi, D Pascal, S. Raimondo, M. El Soury, C.A. Budau, D. Visigalli, L. Nobbio, A. Schenone, S. Geuna - Regulation of the NRG1/ErbB system in CMT1a peripheral nerves, 6th International Charcot-Marie-Tooth and related neuropathy consortium (CMTR) meeting, Venice-Mestre, 8-10 september, 2016.  Journal of the Peripheral Nervous System 21:229-314 (2016). 

13) B.E. Fornasari, G. Gambarotta, G. Ronchi, S. Raimondo, A. Crosio, C.A. Budau, P. Tos, B. Battiston, S. Geuna - Chitosan tubes enriched by skeletal muscle for peripheral nerve regeneration, 6th Vienna Symposium on Surgery of Peripheral Nerves (PNS), Vienna (Austria),  March 17-19, 2017.

14) B.E. Fornasari, G. Ronchi, S. Raimondo, A. Crosio, C.A. Budau, P. Tos, I. Perroteau, B. Battiston, S. Geuna, G. Gambarotta - Fresh skeletal muscle fibers as internal filler of chitosan tubes for nerve repair, 4th International Symposium on Peripheral Nerve Regeneration (ISPNR), Barcellona (Spagna), July 6-8, 2017. (ORAL SPEECH)

15) M. Morano, B. E. Fornasari, S. Gnavi, C. Riccobono, C. Tonda-Turo, M. Zanetti, G. Ciardelli and S. Geuna-The influence of gelatin fibres topography and growth factors on dorsal root ganglia neurons, 4th International Symposium on Peripheral Nerve Regeneration (ISPNR), Barcellona (Spagna), July 6-8, 2017.

16)  B.E. Fornasari, G. Ronchi, S. Raimondo, A. Crosio, C.A. Budau, P. Tos, I. Perroteau, B. Battiston, S. Geuna, G. Gambarotta -Fresh skeletal muscle fibres as internal filler of chitosan tubes for primary and delayed nerve repair,-XVII SINS National Congress, Lacco Ameno (Italia), October 1-4,2017

17) B.E. Fornasari, G. Ronchi, S. Raimondo, G. Gambarotta, M. Cillino, P. Pugliese, A.Cordova, F. Moschella, P. Tos, S. Geuna - Delayed nerve repair negatively affects peripheral nerve regeneration and functional recovery, 27° Congresso Nazionale Società Italiana di Microchirurgia (SIM), Mondello (Italy),October 26-28, 2017 

 

-2end International Symposium on Peripheral Nerve Regeneration, 23-25 January, Turin

- 1st International Workshop on "Intrinsic and extrinsic mechanism of axonal regeneration", may 27th 2014, Brussels

-FENS 6-9 July, Milan

- XXIV Convegno Nazionale Gruppo Italiano per lo Studio della Neuromorfologia (G.I.S.N.) Bologna, November 28-29, 2014.

-Quinta Riunione Annuale dell'Associazione italiana per lo studio del Sistema Nervoso Periferico (ASNP). Torino, April 9 - 11, 2015.

-Summer School Transkills: competenze strategiche per giovani ricercatori. Villa Vigoni (Lago di Como), July 8-11  2015. 

-3nd International Symposium on Peripheral Nerve Regeneration, Hannover (Germany), September 23-25, 2015.

- 27° Congresso Nazionale della Società  Italiana di Microchirurgia (SIM), Turin (Italy), November 26-28, 2015.

-NIS COLLOQUIUM "L'interazione fra nano-oggetti e neuroni: dalla biofisica alla nanomedicina", Torino, Sala dei mappamondi, Accademia delle Scienze di Torino, November 30, 2015 

-"ENABLING TECHNOOGIES IN 3D CANCER ORGANOID", Turin(MBC, via izza 52), March 8-9, 2016

-European Chapter Meeting of the Tissue Engineering and Regenerative Medicine International Society (TERMIS-EU 2016), Uppsala (Sweden), June 28- July 1, 2016.

-6th Vienna Symposium on Surgery of Peripheral Nerves (PNS), Vienna (Austria), March 17-19, 2017.

- 4th International Symposium on Peripheral Nerve Regeneration (ISPNR), Barcellona (Spagna),July  6-8, 2017

 -XVII SINS (Società italiana Neuroscienze) National Congress, Lacco Ameno (Italia), October 1-4,2017

-Congresso Nazionale Società Italiana di Microchirurgia (SIM), Mondello (Italy),October 26-28, 2017 

-"International Stereology Course" S. Geuna, Dipartimento di Scienze cliniche e biologiche, Università di Torino. January 27-28, 2014

-"Mechanisms of cortical plasticity: from the visual to the motor cortex" M. Caleo, Istituto di Neuroscienze, CNR, Pisa. NICO, Torino. April 4, 2014

- "Pluripotent stem cells as a model of in vitro neurogenesis" Federico Cremisi, Ricercatore della Classe di Scienze, Scuola Normale Superiore di Pisa. 30 May 2014- NICO

- "The role of thalamic imputs in the development of the prefrontal cortex and its relevance in schizofrenia" Zakaria Ouaz, dottorando Università Cadi Ayyad di Marrakech. 4 June 2014 - NICO

-"Genome-wide activity of unliganded Estrogen Receptor alpha in breast cancer cells" Livia Caizzi, Post-doc fellow, Departement of Molecular Biology Max Plank Institute for Biophysical Chemistry Gottingen, Germany, 20 October 2014- Palazzina Polo Biologico

-"Cytoskeletal Mechanisms of Axon Growth and Regeneration" Frank Bradke (German Center for Neurodegenerative Diseases, Bonn). 9 February 2015, Azienda Ospedaliero-Universitaria San Luigi Gonzaga

-"Molecular fine-tuning in the perineuronal nets orchestrate plasticity and repair in the CNS" Jessica Kwok,  John van Geest Centre for Brain Repair, University of Cambridge (UK), NICO 23 February 2015

-"Linking fatty acid metabolism to peripheral neuropathy" Mirco Nitro, Department of Pharmacological and Biomolecular Sciences, University of Milan, NICO 27 February 2015

-"Extrinsic mechanisms regulate the GPR17 receptor during oligodendrocyte precursor cell maturation: implications for the development of new remyelinating strategies" Marta Fumagalli (Laboratory of Molecular and Cellular Pharmacology of Purinergic Transmission, Department of Pharmacological and Biomolecular Sciences, University of Milan). NICO, Torino. April 17, 2015

- "Optogenetic Regulation of Transcription: modulation of the RE1-Silencing Transcription Factor (REST) and its possible applications in brain diseases" Fabio Benfenati, Professor of Neurophysiology, University of Genova, Department od Neuroscience and brain technologies, the italian institute of technology. 22th May 2015

- "Dissecting Alternative Pathways and Functions of the microRNA biogenesis machinery in mammalian neurogenesis and neurodevelopmental disorders, Davide De Petri Tonelli, Neurobiology of miRNAs lab. Istituto di Tecnologia, Genova, NICO, Torino. 4th june 2015.

- "The role of the extracellular matrix molecule Bral1 in the nodes of Ranvier and action potential conduction" Toshitaka Oohashi, Department of Molecular Biology and Biochemistry, Okayama University, Japan, NICO, Torino. 12th June 2015 

- "Glio-trasmettitori nel sistema nervoso periferico", Valerio Magnaghi, Department of Pharmacological and Biomolecular Sciences, University of Milan, 10th July 2015 

- "The protein quality control system in motoneuron diseases" Angelo Poletti, Department of Pharmacological and Biomolecular Sciences, University of Milan, NICO 11th September 2015

-TRAINING COURSE OF PERSONS CARRYING OUT ANIMAL EXPERIMENTS, organized by the Neuroscience Institute Cavalieri-Ottolenghi (NICO). 10, 19, 23th June, 2nd July and 15th Dicember 2015

-"Gli anticorpi intracellulari come potenziali strumenti terapeutici per le malattie neurodegenerative" Alessio Cardinale, Laboratory of Molecular and Cellular Neurobiology, Istituto San Raffaele (Roma); NICO, 22th January 2016  

-"NGF and neuro-behavioural plasticity: coping with stress in mice, rats and parachutists" Enrico Alleva, Director, Section of Behavioural Neurosciences- Istituto Superiore di Sanità(Roma); Adjunct Professor of Ethology at "Sapienza" University of Rome; NICO 18th October 2016

-"NGF and neuro-behavioural plasticity: coping with stress in mice, rats and parachutists" Enrico Alleva, Director, Section of Behavioural Neurosciences- Istituto Superiore di Sanità(Roma); Adjunct Professor of Ethology at "Sapienza" University of Rome; NICO 18th October 2016

- "Two photon microscopy for in vivo functional imaging" , Serena Bovetti, IIT Genova; Aula C, Department of life sciences and systems biology; December 16, 2016.

- "How stem cells signal to host immune" - Stefano Pluchino, Department of Clinical Neuroscience, Cambridge, UK; NICO, Orbassano, March 16, 2017

- "Introduction of Kyutech & inorganic-organic hybrids for bone and nerve regeneration" Yuki Shirosaki, Kyushu Institute of Technology Fukuoka, Japan; Aula Seminari Department of Clinical and Biological Sciences , Orbassano (TO) April 12, 2017

- "Gene Regulation of Functional Brain Networks" Michele Caselle, Università di Torino, Dipartimento di Fisica e INFN; NICO, Orbassano, May 11, 2017

- "Neuronal signalling pathway responsiveness to temporally-encoded inputs - new insights and new tools" Michael Courtney, Turku Centre for Biotechnology, University of Turku and Abo Academy University, Finland; NICO - Orbassano, May 26, 2017

- "Novel models of stretch-induced injury in mouse oligodendrocytes and organotypic culture of cerebellar slices: study of pathophysiological mechanisms" Elena Chierto, Paris Descartes University; NICO, September 22, 2017.

 

-Contributo giovani ricercatori(TRAVEL GRANT) per XXIV Convegno Nazionale Gruppo Italiano per lo Studio della Neuromorfologia, Italy, 28-29 November 2014

- European Society for the Study of Peripheral Nerve Repair and Regeneration (ESPNR), from May 2014

- Società italiana di neuroscienze (SINS), from May 2017  

 

benedetta.fornasari@gmail.com

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