1999-2002: PhD in Physiology, Dept. of General Physiology and Biochemistry. University of Milano.

2002-2004: Postdoctoral Fellow, Laboratory of Molecular Physiology and Neurobiology, Dept. of General Physiology and Biochemistry, University of Milano.

2004-2009: Postdoctoral Fellow in the Molecular Neurogenetic Unit, IRCCS Foundation Neurological Institute “C. Besta”.

2009-2013: Staff Scientist in the Molecular Neurogenetic Unit, IRCCS Foundation Neurological Institute “C. Besta”.

2013-2019: Senior Investigating Scientist, MRC - Mitochondrial Biology Unit, Cambridge, UK.

2020-present: Associate Professor in Genetics, Department of Biomedical Sciences, University of Padova, IT

After a PhD in Physiology, Prof Viscomi entered the mitochondrial medicine field in 2004 as a postdoc in Dr Massimo Zeviani’s lab at the Neurological Institute “C. Besta” in Milan, Italy, where in 2009 he was appointed as a junior group leader. His main research interest since then has been focused on translational aspects with the ultimate goals of clarifying the biological basis of human diseases and developing innovative and effective therapies. To this end, he developed and characterized a panel of animal models of mitochondrial disease to investigate the molecular pathogenesis of the corresponding human syndrome. Building on the knowledge of the mechanisms leading to disease, he developed new therapeutic approaches using both pharmacological and gene therapy strategies. The main achievements of these researches have been (i) the discovery of the pathogenetic mechanism of ethylamalonic encephalopathy (EE), i.e. the accumulation of the powerful cytochrome c oxidase inhibitor hydrogen sulfide (H2S) (Tiranti et al, Nat Med, 2009) (ii) the development of a therapy based on N-acetylcysteine and metronidazole highy effective in the treatment of EE in mice and, most importantly, patients (Viscomi et al, Nat Med, 2010) (iii) the discovery that the stimulation of the PGC1alpha-dependent mitochondriogenic pathway by using either the AMPK agonist AICAR or the NAD⁺ precursor Nicotinamide Riboside (NR) was effective in ameliorating the phenotype in mouse models of cytochrome c oxidase deficiency (Viscomi et al, Cell Metab, 2011; Cerutti et al, Cell Metab, 2013) (iv) the development of AAV-mediated gene therapy approaches to treat mitochondrial diseases due to accumulation of toxic compounds, such as EE and mitochondrial gastro-intestinal-encephalomyopathy (MNGIE) (Di Meo et al, EMBO Mol Med, 2012; Torres-Torronteras et al, Mol Ther, 2014). More recently, his laboratory has demonstrated the potential of AAV-based gene therapy in other mitochondrial diseases due to defects in nuclear genes (Bottani et al, Mol Ther, 2014, Di Meo et al, Gene Therapy, 2017, Pinheiro et al, Mol Ther, 2020). Finally, in collaboration with Michal Minczuk, MBU, Cambridge, UK, he helped develop an AAV-based approach to correct specific mtDNA mutations through the use of Zinc-finger Nucleases (Gammage et al Nat Med, 2018). These studies constitute proof of fundamental principle for the transfer of these therapies to humans in the years to come.

Other studies that we carried out in my laboratory were aimed at studying the possibility of by-passing respiratory chain defects through the use of alternative oxidases (Dogan et al, Cell Metab, 2018), defining the mechanism by which rapamycin improves the phenotype of various mouse models of mitochondrial disease (Civiletto et al, EMBO Mol Med 2018), and the possibility to shape mitochondrial cristae to correct mitochondrial defects (Civiletto et al, Cell Metab, 2015; Luna-Sanchez et al, Mol Ther, 2020)

Finally, I have collaborated on numerous studies to define the functional role of various disease genes (Signes et al, EMBO Mol Med, 2019, Bottani et al, Mol Ther, 2017, Brunetti et al, EMBO Mol Med 2016).

1. Peruzzo R, Corrà S, Costa R, Brischigliaro M, Varanita T, Biasutto L, Rampazzo C, Ghezzi D, Leanza L, Zoratti M, Zeviani M, De Pittà C, Viscomi C, Costa R, Szabò I. Exploiting pyocyanin to treat mitochondrial disease due to respiratory complex III dysfunction. Nat Commun. 2021 Apr 8;12(1):2103

2. Peruzzotti-Jametti L, Bernstock JD, Willis CM, Manferrari G, Rogall R, Fernandez-Vizarra E, Williamson JC, Braga A, van den Bosch A, Leonardi T, Krzak G, Kittel Á, Benincá C, Vicario N, Tan S, Bastos C, Bicci I, Iraci N, Smith JA, Peacock B, Muller KH, Lehner PJ, Buzas EI, Faria N, Zeviani M, Frezza C, Brisson A, Matheson NJ, Viscomi C, Pluchino S. Neural stem cells traffic functional mitochondria via extracellular vesicles. PLoS Biol. 2021 Apr 7;19(4):e3001166. doi: 10.1371/journal.pbio.3001166.

3. Yin Z, Burger N, Kula-Alwar D, Aksentijević D, Bridges HR, Prag HA, Grba DN, Viscomi C, James AM, Mottahedin A, Krieg T, Murphy MP, Hirst J. Structural basis for a complex I mutation that blocks pathological ROS production. Nat Commun. 2021 Jan 29;12(1):707. doi: 10.1038/s41467-021-20942-w

4. Pérez MJ, Ivanyuk D, Panagiotakopoulou V, Di Napoli G, Kalb S, Brunetti D, Al-Shaana R, Kaeser SA, Fraschka SA, Jucker M, Zeviani M, Viscomi C, Deleidi M. Loss of function of the mitochondrial peptidase PITRM1 induces proteotoxic stress and Alzheimer's disease-like pathology in human cerebral organoids. Mol Psychiatry. 2020 Jul 7. doi: 10.1038/s41380-020-0807-4.

5. Luna-Sanchez M, Benincá C, Cerutti R, Brea-Calvo G, Yeates A, Scorrano L, Zeviani M, Viscomi C. Opa1 Overexpression Protects from Early-Onset Mpv17^-/--Related Mouse Kidney Disease. Mol Ther. 2020 Aug 5;28(8):1918-1930. doi: 10.1016/j.ymthe.2020.06.010

6. Silva-Pinheiro P, Cerutti R, Luna-Sanchez M, Zeviani M, Viscomi C. A Single Intravenous Injection of AAV-PHP.B-<i>hNDUFS4</i> Ameliorates the Phenotype of Ndufs4^-/- Mice. Mol Ther Methods Clin Dev. 2020 May

4;17:1071-1078. doi: 10.1016/j.omtm.2020.04.026

7. Signes A, Cerutti R, Dickson AS, Benincá C, Hinchy EC, Ghezzi D, Carrozzo R, Bertini E, Murphy MP, Nathan JA, Viscomi C, Fernandez-Vizarra E, Zeviani M. APOPT1/COA8 assists COX assembly and is oppositely regulated by UPS and ROS. EMBO Mol Med. 2019 Jan;11(1):e9582. doi: 10.15252/emmm.201809582

8. Civiletto G, Dogan SA, Cerutti R, Fagiolari G, Moggio M, Lamperti C, Benincá C, Viscomi C, Zeviani M. Rapamycin rescues mitochondrial myopathy via coordinated activation of autophagy and lysosomal biogenesis. EMBO Mol Med. 2018 Nov;10(11):e8799. doi: 10.15252/emmm.201708799

9. Gammage PA, Viscomi C, Simard ML, Costa ASH, Gaude E, Powell CA, Van Haute L, McCann BJ, Rebelo-Guiomar P, Cerutti R, Zhang L, Rebar EJ, Zeviani M, Frezza C, Stewart JB, Minczuk M. Genome editing in mitochondria corrects a pathogenic mtDNA mutation in vivo. Nat Med. 2018 Nov;24(11):1691-1695. doi:10.1038/s41591-018-0165-9

10. Dogan SA, Cerutti R, Benincá C, Brea-Calvo G, Jacobs HT, Zeviani M, Szibor M, Viscomi C. Perturbed Redox Signaling Exacerbates a Mitochondrial Myopathy. Cell Metab. 2018 Nov 6;28(5):764-775.e5. doi: 10.1016/j.cmet.2018.07.012

- University of Padova

- Telethon

- Associazione Luigi Comini Onlus