Lab Valente

Enza Maria Valente, PI

Email: enzamaria.valente@unipv.it

Valentina Serpieri, post-doc

Fulvio D'Abrusco, PhD student

Lidia Pollara, PhD student

Francesco Brunelli, PhD student

Giada Cuconato, PhD student

Concetta Mazzotta, PhD student

Alberto Imarisio, assegnista di ricerca

Caterina Galandra, data manager

Davide Franzone, borsista

Alessia Orsi, borsista

The Valente Lab has been carrying out for many years a translational research, which starts from the recruitment and clinical characterization of patients affected by rare neurogenetic disorders, to identify the underlying genetic cause, describe genotype-phenotype correlates and understand the pathogenetic mechanisms through functional studies, often based on patient-derived cell models.

Over the years, the Lab has dealt with several rare neurologic diseases, focusing on cerebral and cerebellar congenital malformations, pediatric ataxias, and Parkinson disease. In particular, the Valente Lab has been researching for over 20 years Joubert syndrome, a ciliopathy characterized by a unique cerebellar malformation and wide clinical and genetic heterogeneity. In this field, the Lab is internationally recognized as a reference center, contributing to describe the epidemiology and natural history of this syndrome, identify several disease-genes, define major genotype-phenotype correlates and understand key pathogenetic mechanisms related to the dysfunction of primary cilia.

A second relevant line of research dwells on hereditary forms of Parkinson disease, with a long-term focus on the PINK1 gene: following its discovery back in 2004, the Valente Lab has widely contributed to define the clinical picture and mutational spectrum related to this gene, and to identify novel interactors and neuroprotective functions at the neuronal level. Besides the PINK1 gene, research is also active on other genetic forms of Parkinson disease, such as those associated to the PARK2 and GBA genes, other of inherited movement disorders and rare neurodevelopmental disorders characterized by complex brain malformations.

The Lab has been funded by the European Research Council, and it is now funded by the Ministry of Health (with national and European projects), and by Telethon, Cariplo and Mariani Foundations.

Brunelli F, Torosantucci L, Gelmetti V, Franzone D, Grünewald A, Krüger R, Arena G, Valente EM. PINK1 Protects against Staurosporine-Induced Apoptosis by Interacting with Beclin1 and Impairing Its Pro-Apoptotic Cleavage. Cells. 2022 Feb 15;11(4):678.

Nuovo S, Micalizzi A, Romaniello R, Arrigoni F, Ginevrino M, Casella A, Serpieri V, D'Arrigo S, Briguglio M, Salerno GG, Rossato S, Sartori S, Leuzzi V, Battini R, Ben-Zeev B, Graziano C, Mirabelli Badenier M, Brankovic V, Nardocci N, Spiegel R, Petković Ramadža D, Vento G, Marti I, Simonati A, Dipresa S, Freri E, Mazza T, Bassi MT, Bosco L, Travaglini L, Zanni G, Bertini ES, Vanacore N, Borgatti R, Valente EM. Refining the mutational spectrum and gene-phenotype correlates in pontocerebellar hypoplasia: results of a multicentric study. J Med Genet. 2022 Apr;59(4):399-409.

Serpieri V, D'Abrusco F, Dempsey JC, Cheng YH, Arrigoni F, Baker J, Battini R, Bertini ES, Borgatti R, Christman AK, Curry C, D'Arrigo S, Fluss J, Freilinger M, Gana S, Ishak GE, Leuzzi V, Loucks H, Manti F, Mendelsohn N, Merlini L, Miller CV, Muhammad A, Nuovo S, Romaniello R, Schmidt W, Signorini S, Siliquini S, Szczałuba K, Vasco G, Wilson M, Zanni G, Boltshauser E, Doherty D, Valente EM. SUFU haploinsufficiency causes a recognisable neurodevelopmental phenotype at the mild end of the Joubert syndrome spectrum. J Med Genet. 2021 Oct 21:jmedgenet-2021-108114.

Petrucci S, Ginevrino M, Trezzi I, Monfrini E, Ricciardi L, Albanese A, Avenali M, Barone P, Bentivoglio AR, Bonifati V, Bove F, Bonanni L, Brusa L, Cereda C, Cossu G, Criscuolo C, Dati G, De Rosa A, Eleopra R, Fabbrini G, Fadda L, Garbellini M, Minafra B, Onofrj M, Pacchetti C, Palmieri I, Pellecchia MT, Petracca M, Picillo M, Pisani A, Vallelunga A, Zangaglia R, Di Fonzo A, Morgante F, Valente EM. GBA-Related Parkinson's Disease: Dissection of Genotype-Phenotype Correlates in a Large Italian Cohort. Mov Disord. 2020 Nov;35(11):2106-2111.

De Mori R, Severino M, Mancardi MM, Anello D, Tardivo S, Biagini T, Capra V, Casella A, Cereda C, Copeland BR, Gagliardi S, Gamucci A, Ginevrino M, Illi B, Lorefice E, Musaev D, Stanley V, Micalizzi A, Gleeson JG, Mazza T, Rossi A, Valente EM. Agenesis of the putamen and globus pallidus caused by recessive mutations in the homeobox gene GSX2. Brain. 2019 Oct 1;142(10):2965-2978.