Education:
1989: High School Diploma Liceo Classico “Dante Alighieri”, Rome (Italy)
1996: Master in Science in Biological Sciences, University of Rome “La Sapienza”, Rome (Italy)
2000: PhD in Molecular and Cellular Biology, University of Milan (Italy)

Positions:
2001-2005: Post-Doc Fellow, S. Raffaele Scientific Institute, Milan (Mentor: Lawrence Wrabetz, MD)
2005-2008: Visiting Post-Doc Fellow, NIH-NINDS (Mentor: Kenneth Fischbeck, MD)
2008-2009: Staff Scientist, Dptm of Neurology, U. of Pennsylvania (Mentor: Dr J.P. Taylor, MD, PhD)
2009-2014: Group Leader, Italian Institute of Technology, Genoa, Italy
2013-2017: Assistant and Associate Professor, CIBIO, University of Trento, Trento, Italy
2017-present: Associate Professor, Department of Biomedical Sciences, University of Padova, Italy

Performed research stages at:
NINDS, National Institutes of Health, Bethesda, MD USA with Kenneth Fischebck, University of Pennsylvania, Philadelphia USA with J. Paul Taylor

Brain folding diseases, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), and polyglutamine diseases, are a broad class of neurodegenerative disorders. These diseases are characterized by selective degeneration of specific neuronal populations in the central nervous system. The basis for selective neuronal vulnerability remains an enigma. Polyglutamine diseases are a family of nine neurodegenerative diseases, including spinal and bulbar muscular atrophy (SBMA), Huntington’s disease (HD), DRPLA, and six types of spinocerebellar ataxia. Polyglutamine diseases are caused by expansion of the CAG repeat encoding glutamine in the coding region of specific genes. Amyotrophic lateral sclerosis (ALS) is characterized by the selective loss of upper and lower motor neurons and skeletal muscle atrophy, wasting and paralysis with death of patients occurring in about three-five years from diagnosis. The majority of cases are sporadic (sALS), while a restricted number of cases is familial (fALS). sALS is a complex disease that is thought to result from the interplay between environmental and genetic factors. Our laboratory focuses on the elucidation of the molecular mechanisms underlying the degeneration and death of neurons with the aim to develop novel potential therapeutic strategies for these incurable disorders.

Project 1:
Using SBMA and HD as models of polyglutamine diseases and motor neuron disease, we study the relevance of the functional relationship between protein function and structure on disease pathogenesis. We aim at identifying post-translational modifications (PTMs) of the disease proteins that either enhance or suppress neurodegeneration, and use this information to identify drugs that activate cellular pathways to induce or attenuate such PTMs for therapy development.

Project 2:
Using inducible animal models of SBMA for spatial and temporal control of expression of the disease protein, we explore the role of peripheral tissues, such as skeletal muscle, to the pathogenesis of neuromuscular diseases. In addition, we investigate the molecular details of communication between neurons and non-neuronal cells and the relevance of metabolic tissues in neuromuscular diseases.

Major contributions:
1997-2003 Showed that Synaptophyin regulates the sorting of Synaptobrevin to synaptic vesicles.
2008 Showed that demyelination is linked to endoplasmic reticulum stress, unfolded protein response and altered protein quality control in peripheral neuropathies.
2009 Showed that IGF-1/AKT modifies the pathogenesis of SBMA through direct phosphorylation of the disease protein, namely the androgen receptor.
2013-2015 Showed that arginine methylation is a key PTM in neurodegenerative diseases.
2017 Showed that PACAP/AC/PKA/CDK2 axis has a key role in neurodegeneration.

1. Polanco MJ, Parodi S, Piol D, Stack C, Chivet M, Contestabile A, Miranda HC, Lievens PMJ, Espinoza S, Jochum T, Rocchi A, Grunseich C, Gainetdinov RR, Cato ACB, Lieberman A, La Spada AR, Sambataro F, Fischbeck KH, Gozes I, Pennuto M*. (2016) CDK2 inhibition by PACAP/AC/PKA signaling reduces polyglutamine-expanded androgen receptor phosphorylation and toxicity in SBMA. Sci Transl Med 8:370ra181.
2. Rocchi A, Milioto C, Parodi S, Armirotti A, Borgia D, Pellegrini M, Urciuolo A, Molon S, Morbidoni V, Marabita M, Romanello V, Gatto P, Blaauw B, Bonaldo P, Sambataro F, Robins DM, Lieberman AP, Sorarù G, Vergani L, Sandri M, Pennuto M*. (2016) Glycolytic-to-oxidative fiber-type switch and mTOR signaling activation are early-onset features of SBMA muscle modified by high-fat diet. Acta Neuropathol 132:127-44.
3. Scaramuzzino C, Casci I, Parodi S, Lievens PMJ, Polanco MJ, Milioto C, Chivet M, Monaghan J, Mishra A, Badders N, Aggarwal T, Grunseich C, Sambataro F, Basso M, Fackelmayer FO, Taylor JP, Pandey UB, Pennuto M*. (2015) Protein arginine methyltransferase 6 enhances polyglutamine-expanded androgen receptor function and toxicity in spinal and bulbar muscular atrophy. Neuron 85: 88-100.
4. Palazzolo I, Stack C, Kong L, Musaro M, Adachi H, Katsuno M, Sobue G, Taylor JP, Sumner JC, Fischbeck HK, Pennuto M* (2009) Overexpression of muscle-specific isoform of IGF-1 in the skeletal muscle of SBMA mice extends life and attenuates disease manifestations. Neuron 63: 316-28.
5. Pennuto M, Tinelli E, Malaguti M, Del Carro U, D'Antonio M, Ron D, Quattrini A, Feltri ML, Wrabetz L. (2008) Ablation of the UPR-mediator CHOP restores motor function and reduces demyelination in Charcot-Marie-Tooth 1B mice. Neuron 57:393-405.

Telethon-Italy

Ministero della Salute

Muscular Dystrophy Association-USA

Association Fracaise Myopathies-France