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Istituto Veneto di Scienze, Lettere ed Arti - Testata per la stampa

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Paolo Bernardi

Paolo Bernardi

Professore ordinario di Patologia generale nell'UniversitÓ degli studi di Padova.

- s.c.r. 27 settembre 2006, s.e. 30 aprile 2015

STUDIES
High School Diploma Liceo Classico "Paolo Diacono", Cividale del Friuli (Italy) 1971
M.D. Degree University of Padova (Italy), cum laude 1978
APPOINTMENTS
1979 – 1987: Assistant Professor, University of Padova Medical School
1988 – 1999: Associate Professor, University of Padova Medical School
2000 – present: Full Professor, University of Padova Medical School
2001 – 2004: Deputy Dean of the Medical Faculty, University of Padova
2003 – 2009: Chairman, Department of Biomedical Sciences, University of Padova
2012 – present: Coordinator, Ph.D. Program in Biomedical Sciences, University of Padova
2012 – present: Director, Postgraduate School of Clinical Pathology, University of Padova
HONORS
1984: EMBO Fellow, University of Helsinki, Finland
1985 – 87: Fogarty Fellow, Whitehead Institute for Biomedical Research, Cambridge Massachusetts, USA
2006 – 2010: Council Member, Bioenergetics Subgroup, Biophysical Society USA
2006 – 2014: Socio Corrispondente, Istituto Veneto di Scienze, Lettere ed Arti, Venice
2008: Visiting Professor, Oregon Clinical and Translational Research Institute, Portland, Oregon, USA
2009 – 2011: Council Member, Associazione di Biologia Cellulare e del Differenziamento
2009 – present: Member, Confrérie des Chevaliers de Tastevin, Château Clos Vougeot, Bourgogne, France
2010 – 2013: President, Italian Group of Biomembranes and Bioenergetics
2010 – present: Member, Academia Europaea, Section for Biochemistry and Molecular Biology
2012: Prize for Physiology and Pathology, Ministro Beni e Attivit? Culturali, Accademia Nazionale dei Lincei, Rome
2014 – present: Council Member, Bioenergetics Subgroup, Biophysical Society USA
2015 – present: Socio Effettivo, Istituto Veneto di Scienze, Lettere ed Arti, Venice
SCIENTIFIC INTERESTS AND CAREER HIGHLIGHTS
Paolo Bernardi began his studies on mitochondrial physiology and ion transport under the guidance of Giovanni Felice Azzone, one of the founding Fathers of Bioenergetics. His education in Cellular and Molecular Biology was completed with a long-term stay at the Whitehead Institute for Biomedical Research - Massachusetts Institute of Technology, where he worked under the supervision of Harvey F. Lodish. He pioneered the field of mitochondrial channels and their role in cellular pathophysiology. In particular, he focused on the permeability transition pore (PTP), a high conductance channel that is increasingly recognized as a key player in cell death. During the early 1990s he defined key points of regulation of the PTP in isolated mitochondria (membrane potential, matrix pH, Me2+-binding sites, specific redox-sensitive sites). He then developed tools to reliably monitor mitochondrial function in situ, and addressed mechanistic questions on the PTP as a target in degenerative diseases and cancer. His studies have been extended to in vivo models, and led to the demonstration that early mitochondrial adaptation plays a key role in hepatocarcinogenesis [Kl?hn et al. (2003) Proc Natl Acad Sci USA 100, 10014-10019] and in onset of the Warburg effect [Sciacovelli et al. (2013) Cell Metab 17, 988-999]; and that mitochondrial dysfunction mediated by the PTP unexpectedly causes muscular dystrophy in collagen VI deficiency [Irwin et al. (2003) Nat Genet 35, 367-371; Angelin et al. (2007) Proc Natl Acad Sci USA 104, 991-996; Merlini et al. (2008) Proc Natl Acad Sci USA 105, 5225-5229]. These studies paved the way to a potential therapy of Ullrich Congenital Muscular Dystrophy and Bethlem Myopathy with NIM811, a non immunosuppressive analog of cyclosporin A [Zulian et al. (2014) Hum Mol Genet 23, 5353-5363]. The recent identification of the PTP, which appears to originate from dimers of the FOF1 ATP synthase [Giorgio et al. (2013) Proc Natl Acad Sci USA 110, 5887-5892; Carraro et al. (2014) J Biol Chem 23, 15980-15985; von Stockum et al (2015) J Biol Chem 290, 4537-4544], offers great promise for further molecular definition of the pore and of its function in health and disease.
Paolo Bernardi was a major actor in the Mitochondrial Renaissance of the 1990s. As early as 1992 he was one of the few to realise the importance of mitochondria in cell death well before the role of cytochrome c release was shown to be a key event in apoptosis. He pioneered the field rapidly reaching international recognition, as testified by 180 invited lectures at meetings and 121 seminars at prestigious Institutions worldwide. He has organized or coorganized key meetings on mitochondrial pathophysiology that significantly contributed to the continuing success of the field (2 meetings on New Perspectives in Mitochondrial Research, Padova, Italy 1993 and 1997; Colloquium Mitochondria in Cell Death, 8th European Bioenergetics Conference, Valencia, Spain 1994; Colloquium The Mitochondrial Permeability Transition in Accidental and Programmed Cell Death, 9th European Bioenergetics Conference, Louvain-la-Neuve, Belgium 1996; 1st (1996), 2nd (1998) and 3rd (2000) Conference Frontiers in Mitochondrial Research, Albany, NY; Symposium New Frontiers in Mitochondrial Research – from Bioenergetics to Dynamics, Bertinoro, Italy 2007; 52nd, 54th and 58th Annual Meeting of the Biophysical Society USA, Bioenergetics Subgroup Meetings Mitochondria Bioenergetics in Disease and Therapeutics (Long Beach, 2008), Mitochondria in Disease (San Francisco, 2010) and Ion Channels in the Inner Mitochondrial Membrane (San Francisco, 2014). He is the coorganizer of the 2015 Cold Spring Harbor China on Mitochondria and the organizer of the 2016 European Bioenergetics Conference. His achievements were possible through the work and training of junior personnel (from 1991 Prof. Bernardi has supervised the work of 28 Graduate Students from the University of Padova, 4 visiting Graduate Students from other Universities and 13 postdoctoral Fellows).
EDITORIAL ACTIVITIES
1. Chief Specialty Editor, Frontiers in Mitochondrial Research (from 2012) for Frontiers in Physiology.
2. Section Editor, Pathobiology of Human Disease: A Dynamic Encyclopedia of Disease Mechanisms, Elsevier.
3. Editorial Board Member: Journal of Biological Chemistry (1997-2002, 2003-2008, 2010-present), Biochimica et Biophysica Acta (1999-present), Pharmacological Research (2015-present), Archives of Biochemistry and Biophysics (1998-2003), IUBMB Life (2002-2007).
4. Guest Editor: Biochimica et Biophysica Acta "Mitochondria in Cell Death" (1998); BioFactors "New Perspectives in Mitochondrial Research" (1998); IUBMB Life Special Issue "Perspectives in Mitochondrial Research" (2001). 5. Member of the Education Committee, International Union of Biochemistry and Molecular Biology (1998-2003).
FUNDING
Ministry for the University and Scientific Research – Italy; University of Padova; Telethon – Italy; National Institutes of Health - Public Health Service (USA); AIRC (Italian Association on Cancer Research); Fondazione Cassa di Risparmio di Padova e Rovigo.
BIBLIOMETRIC INDICATIONS
As of May, 2015 Prof. Bernardi has published 215 peer-reviewed articles which have about 22,000 citations with an H index of 75 (Google Scholar). His most quoted paper [Bernardi P (1999) Mitochondrial transport of cations: Channels, exchangers and permeability transition. Physiol Rev 79, 1127-1155] has 1,269 citations; his most quoted experimental paper [Basso, E., Fante, L., Fowlkes, J., Petronilli, V. Forte, M.A. and Bernardi, P. (2005) Properties of the Permeability Transition Pore in Mitochondria Devoid of Cyclophilin D, J Biol Chem 280, 18558-18561] ranks 5th with 570 quotes. His "top ten" list gathers over 6,200 quotes.
SELECTED PUBLICATIONS (from a total of 215)
• Bernardi, P., Rasola, A., Forte, M. and Lippe, G. (2015) The Mitochondrial Permeability Transition Pore: Channel Formation by F-ATP Synthase, Integration in Signal Transduction and Role in Pathophysiology, Physiol. Rev., in corso di stampa
• von Stockum, S., Giorgio, V., Trevisan, E., Lippe, G., Glick, G.D., Forte, M., Da-Rè, C., Checchetto, V., Mazzotta, G., Costa, R., Szabò, I., and Bernardi, P. (2015) F-ATPase of D. melanogaster Forms 53-Picosiemen (53-pS) Channels Responsible for Mitochondrial Ca2+-induced Ca2+ Release, J. Biol. Chem. 290, 4537-4544
• Zulian, A., Rizzo, E., Schiavone, M., Palma, E., Tagliavini, F., Blaauw, B., Merlini, L., Maraldi, N.M., Sabatelli, P., Braghetta, P., Bonaldo, P., Argenton, F. and Bernardi, P. (2014) NIM811, a cyclophilin inhibitor without immunosuppressive activity, is beneficial in collagen VI congenital muscular dystrophy models, Hum. Mol. Genet. 23, 5353-5363
• Carraro, M, Giorgio, V., ?ileikytė, J., Sartori, G., Forte, M., Lippe, G., Zoratti, M, Szab?, I. and Bernardi, P. (2014) Channel Formation by Yeast F-ATP Synthase and the Role of Dimerization in the Mitochondrial Permeability Transition, J. Biol. Chem. 23, 15980-15985 – paper of the year
• Da-Rè, C., De Pittà, C., Zordan, M.A., Zeviani, M., Teza, G., Nestola, F., Costa, R., and Bernardi, P. (2014) UCP4C mediates uncoupled respiration in larvae of Drosophila melanogaster, EMBO Rep. 15, 586–591 • Giorgio, V., von Stockum, S., Antoniel, M., Fabbro, A., Fogolari, F., Forte, M., Glick, G.D., Petronilli, V., Zoratti, M., Szabó, I., Lippe, G., and Bernardi, P. (2013) Dimers of Mitochondrial ATP Synthase Form the Permeability Transition Pore, Proc. Natl. Acad. Sci. USA 110, 5887-5892
• Bernardi, P. (2013) The mitochondrial permeability transition pore: A mystery solved? Front.Physiol. 4, 95
• Sciacovelli, M., Guzzo, G., Morello, V., Frezza, C., Nannini, N., Calabrese, F., Laudiero, G., Esposito, F., Landriscina, M., Gottlieb, E., Defilippi, P., Bernardi, P.* and Rasola, A.* (2013) The mitochondrial chaperone TRAP1 promotes neoplastic growth by inhibiting succinate dehydrogenase, *Corresponding Authors Cell Metab. 17, 988-999
• Nowikovsky, K., Pozzan, T., Rizzuto, R., Scorrano, L. and Bernardi, P. (2012) The Pathophysiology of LETM1, J. Gen. Physiol. 139, 445-454
• von Stockum, S., Basso, E., Petronilli, V., Sabatelli, P., Forte, M.A., and Bernardi, P. (2011) Properties of Ca2+ Transport in Mitochondria of Drosophila melanogaster, J. Biol. Chem. 286, 41163-41170
• Rasola, A., Sciacovelli, M., Chiara, F., Pantic, B., Brusilow, W.S. and Bernardi, P. (2010) Activation of mitochondrial ERK protects cancer cells from death through inhibition of the permeability transition, Proc. Natl. Acad. Sci. USA 107, 726-731
• Palma, E., Tiepolo, T., Angelin, A., Sabatelli, P., Maraldi, N.M., Basso, E., Forte, M.A., Bernardi, P.* and Bonaldo, P.* (2009) Genetic ablation of cyclophilin D rescues mitochondrial defects and prevents muscle apoptosis in collagen VI myopathic mice, *Corresponding authors Hum. Mol. Genet. 18, 2024-2031
• Merlini, L., Angelin, A., Tiepolo, T., Braghetta, P., Sabatelli, P., Zamparelli, A., Ferlini, A., Maraldi, N.M., Bonaldo, P. and Bernardi, P. (2008) Cyclosporin A corrects mitochondrial dysfunction and muscle apoptosis in patients with collagen VI myopathies, Proc. Natl. Acad. Sci. USA 105, 5225-5229
• Forte, M., Gold, B., Marracci, G., Chandhary, P., Basso, E., Johnsen, D., Yu, X., Fowlkes, J., Bernardi, P. and Bourdette, D. (2007) Cyclophilin D Inactivation Protects Axons in Experimental Autoimmune Encephalomyelitis, an Animal Model of Multiple Sclerosis, Proc. Natl. Acad. Sci. USA 104, 7558-7563
• Angelin, A., Tiepolo, T., Sabatelli, P., Grumati, P., Bergamin, N., Golfieri, C., Mattioli, E., Gualandi, F., Ferlini, A., Merlini, L., Maraldi, N.M., Bonaldo, P. and Bernardi, P. (2007) Mitochondrial dysfunction in the pathogenesis of Ullrich congenital muscular dystrophy and prospective therapy with cyclosporins, Proc. Natl. Acad. Sci. USA 104, 991-996
• Bernardi, P., Krauskopf, A., Basso, E., Petronilli, V., Blachly-Dyson, E., Di Lisa, F. and Forte, M.A. (2006) The mitochondrial permeability transition from in vitro artifact to disease target, FEBS J. 273, 2077-2099 • Giorgio, M., Migliaccio, E., Orsini, F., Paolucci, D., Moroni, M., Contursi, C., Pelliccia, G., Luzi, L., Minucci, S., Marcaccio, M., Pinton, P., Rizzuto, R., Bernardi, P., Paolucci, F. and Pelicci, P.G. (2005) Electron transfer between cytochrome c and p66Shc generates reactive oxygen species that trigger mitochondrial apoptosis, Cell 122, 221-233
• D'Agostino, D.M., Bernardi, P., Chieco-Bianchi, L. and Ciminale, V. (2005) Mitochondria as functional targets of proteins coded by human tumor viruses, Adv. Cancer Res. 94, 87-142
• Penzo, D., Petronilli, V., Angelin, A., Cusan, C., Colonna, R., Scorrano, L., Pagano, F., Prato, M., Di Lisa, F. and Bernardi, P. (2004) Arachidonic Acid Released by Phospholipase A2 Activation Triggers Ca2+-dependent Apoptosis through the Mitochondrial Pathway, J. Biol. Chem. 279, 25219-25225
• Irwin, W., Bergamin, N., Sabatelli, P., Reggiani, C., Megighian, A., Merlini, L., Braghetta, P., Volpin, D., Bressan, G.M., Bernardi, P.*, and Bonaldo, P.* (2003) Mitochondrial dysfunction and apoptosis in myopathic mice with collagen VI deficiency, *Corresponding Authors Nat. Genet. 35, 367-371
• Kl?hn, P.C., Soriano, M.E., Irwin, W., Penzo, D., Scorrano, L., Bitsch, A., Neumann, H.G., and Bernardi, P. (2003) Early resistance to cell death and to onset of the mitochondrial permeability transition during hepatocarcinogenesis with 2-acetylaminofluorene, Proc. Natl. Acad. Sci. USA 100, 10014-10019
• D'Agostino, D.M., Ranzato, L., Arrigoni, G., Cavallari, I., Belleudi, F., Torrisi, M.R., Silic-Benussi, M., Ferro, T., Petronilli, V., Marin, O., Chieco-Bianchi, L., Bernardi, P., and Ciminale, V. (2002) Mitochondrial alterations induced by the p13II protein of human T-cell leukemia virus type 1: critical role of arginine residues, J. Biol. Chem. 277, 34424-34433
• Scorrano, L., Penzo, D., Petronilli, V., Pagano. F., and Bernardi, P. (2001) Arachidonic Acid Causes Cell Death through the Mitochondrial Permeability Transition. Implications for TNF Apoptotic Signaling, J. Biol. Chem. 276, 12035-12040
• Nicholls, D.G., Bernardi, P., Brand, M., Halestrap. A.D., Lemasters, J.J., and Reynolds, I. D. (2000) Apoptosis and the Laws of Thermodynamics. Nat. Cell Biol. 2, E172
• Bernardi, P. (1999) Mitochondrial Transport of Cations: Channels, Exchangers and Permeability Transition. Physiol. Rev. 79, 1127-1155
• Fontaine, E, Ichas, F. and Bernardi, P. (1998) A Ubiquinone-binding Site Regulates the Mitochondrial Permeability Transition Pore. J. Biol. Chem. 273, 25734-25740
• Scorrano, L., Petronilli, V. and Bernardi P. (1997) On the Voltage Dependence of the Mitochondrial Permeability Transition Pore. A Critical Appraisal. J. Biol. Chem. 272, 12295-12299
• Costantini, P., Chernyak, B.V., Petronilli, V. and Bernardi, P. (1996) Modulation of the Mitochondrial Permeability Transition Pore by Pyridine Nucleotides and Dithiol Oxidation at Two Separate Sites. J. Biol. Chem. 271, 6746-6751
• Nicolli, A., Basso, E., Petronilli, V., Wenger, R.M. and Bernardi, P. (1996) Interactions of Cyclophilin with the Mitochondrial Inner Membrane and Regulation of the Permeability Transition Pore, a Cyclosporin A-sensitive Channel. J. Biol. Chem. 271, 2185-2192
• Petronilli, V., Costantini, P., Scorrano, L., Colonna, R., Passamonti, S. and Bernardi, P. (1994) The Voltage Sensor of the Mitochondrial Permeability Transition Pore is Tuned by the Oxidation-Reduction State of Vicinal Thiols. Increase of the Gating Potential by Oxidants and its Reversal by Reducing Agents. J. Biol. Chem. 269, 16638-16642
• Bernardi, P., Veronese, P. and Petronilli, V. (1993) Modulation of the Mitochondrial Cyclosporin A-Sensitive Permeability Transition Pore. I. Evidence for Two Separate Me2+ Binding Sites with Opposing Effects on the Pore Open Probability. J. Biol. Chem. 268, 1005-1010
• Petronilli, V., Cola, C. and Bernardi, P. (1993) Modulation of the Mitochondrial Cyclosporin A-Sensitive Permeability Transition Pore. II. The Minimal Requirements for Pore Induction Underscore a Key Role for Transmembrane Electrical Potential, Matrix pH and Matrix Ca2+. J. Biol. Chem. 268, 1011-1016
• Nicolli, A., Petronilli, V. and Bernardi, P. (1993) Modulation of the Mitochondrial Cyclosporin A-Sensitive Permeability Transition Pore by Matrix pH. Evidence that the Pore Open-Closed Probability is Regulated by Reversible Histidine Protonation. Biochemistry 32, 4461-4465
• Bernardi, P. (1992) Modulation of the Mitochondrial Cyclosporin A-Sensitive Permeability Transition Pore by the Proton Electrochemical Gradient. Evidence that the Pore can be Opened by Membrane Depolarization. J. Biol. Chem. 267, 8834-8839
• Nicolli, A., Redetti, A. and Bernardi, P. (1991) The K+ Conductance of the Inner Mitochondrial Membrane. A Study of the Inducible Uniport for Monovalent Cations. J. Biol. Chem. 266, 9465-9470
• Bernardi, P., Angrilli, A. and Azzone, G.F. (1990) A Gated Pathway for Electrophoretic Na+ Fluxes in Rat Liver Mitochondria. Regulation by Surface Mg2+. Eur. J. Biochem. 188, 91-97
• Bernardi, P., Angrilli, A., Ambrosin, V. and Azzone, G.F. (1989) Activation of Latent K+ Uniport in Mitochondria Treated with the Ionophore A23187. J. Biol. Chem. 264, 18902-18906
• Bernardi, P., Patel, V.P. and Lodish, H.F. (1987) Lymphoid Precursor Cells Adhere to Two Different Sites on Fibronectin. J. Cell Biol. 105, 489-498
• Bernardi, P. (1984) Modulation of Ca2+ Efflux and Rebounding Ca2+ Transport in Rat Liver Mitochondria. Biochim. Biophys. Acta 766, 277-282
• Bernardi, P., Paradisi, V., Pozzan, T. and Azzone, G.F. (1984) Pathway for Uncoupler-Induced Ca2+ Efflux in Rat Liver Mitochondria: Inhibition by Ruthenium Red. Biochemistry 23, 1645-1651
• Bernardi, P. and Azzone, G.F. (1983) Regulation of Ca2+ Efflux in Rat Liver Mitochondria: Role of Membrane Potential. Eur. J. Biochem. 134, 377-383
• Bernardi, P. and Azzone, G.F. (1983) Electroneutral H+/K+ Exchange in Liver Mitochondria: Regulation by Membrane Potential. Biochim. Biophys. Acta 724, 212-223
• Bernardi, P. and Azzone, G.F. (1982) ATP Synthesis During Exogenous NADH Oxidation: a Reappraisal. Biochim. Biophys. Acta 679, 19-27
• Bernardi, P. and Azzone, G.F. (1981) Cytochrome c as an Electron Shuttle Between the Outer and Inner Mitochondrial Membranes. J. Biol. Chem. 256, 7187-7192
• Bernardi, P. and Azzone, G.F. (1979) pH-induced Ca2+ Fluxes in Rat Liver Mitochondria. Eur. J. Biochem. 102, 555-562

 



 
 
 



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