Overview

The laboratory is interested in motor neuron diseases, specifically focusing on the mechanisms contributing to neuronal damage in a non-cell autonomous view. We focus our research on amyotrophic lateral sclerosis (ALS) and Kennedy's disease (also known as spinal and bulbar muscle atrophy or SBMA). We are intrigued by the intercellular communication between motor neurons and surrounding cells like astrocytes and muscle cells and how non-neuronal cells influence neuronal survival. We test our hypothesis in in vitro and in vivo models of disease and in patients’ biofluids.

Research direction

We are developing two major projects:

  • Deciphering the role of non-neuronal cells in Amyotrophic Lateral Sclerosis (ALS) pathobiology.

On one side, we are interested in exploring how glial cells change during disease progression, the mechanisms by which they fail to support neurons over the disease progression, and if these changes could be exploited for disease monitoring in patients. 

  • Investigating if extracellular vesicles are predictive markers of ALS and SBMA.
  • Developing a pre-clinical treatment for skeletal muscle in SBMA. We are attempting to normalize the transcriptional activity of the Androgen Receptor in Kennedy’s disease by modulating the function of its co-activators in the disease.

Group members

  • Manuela Basso, PI
  • Anna Barbieri, PhD student
  • Luisa Donini, PhD student
  • Lorena Pisoni, research fellow
  • Francesca Conci, pre-doctoral fellow
  • Francesco Rosada, research fellow
  • Rossana Borella, research fellow
  • Martina Pessagno, Master student

If you want to know our research project better, contact us. 

Collaborations

  • Maria Pennuto, Università di Padova
  • Carlo Rinaldi, University of Oxford
  • Andrea Calvo, Università di Torino
  • Raffaella Tanel and Riccardo Zuccarino, Ospedale Santa Chiara e Centro NeMO, Trento
  • Nicola Ticozzi, Antonia Ratti, Federico Verde, Ospedale Auxologico, Milan
  • Jessica Mandrioli, Università di Modena-Reggio Emilia
  • Francesco Rinaldi, Università di Padova
  • Alessandro Gori, CNR-SCITEC
  • Fulvio Chiacchiera, Dip. CIBIO
  • Francesca Demichelis, Dip. CIBIO

Funding

Bando: a cascata, fondi PNRR
Title: Metabolic switch in Amyotrophic Lateral Sclerosis and Kennedy's disease
Role: Principal Investigator, monocentric
Period: February-October 2024 

Bando: Ricerca finalizzata Ministero Salute, fondi PNRR
Title: Therapeutic development (TRL4) of muscle-specific microRNAs for Kennedy's disease
Role: Unit, One of four
Period: awarded but not started yet- the grant will last two years 

Bando: Multi-round Telethon 
Title: Targeting overexpressed transcription co-regulators to suppress SBMA
Role: Principal Investigator, monocentric
Period: October 2023-September 2025

Bando: AriSLA 2021
Title: EVTest in ALS- Extracellular vesicles in ALS: testing their use as biomarkers for disease progression
Role: Principal Investigator, coordinator of four units
Period: April 2022-March 2026

Bando: AFM Telethon 2021
Development of a therapeutic strategy to suppress LSD1 and PRMT6-mediated toxic gain of function in SBMA
Role: Partner
Period: March 2023-October 2026
Goal: To ameliorate the strategy to silence PRMT6 and LSD1 in vivo selectively in the muscle

Bando: AriSLA 2021
Title: A Gene therapy Approach Targeting TDP-43 pathology for ALS
Role: Partner
Period: April 2022-March 2026

Bando: PRIN 2022 (D.D. 104/22)
EVALS: Deciphering the role of senescence in glia-to-neuron miscommunication through extracellular vesicles in ALS
Manuela Basso, coordinatrice
Codice Protocollo: 20229HKCRT     CUP: E53D23011240006

Selected publications

Prakasam R, Bonadiman A, Andreotti R, Zuccaro E, Dalfovo D, Marchioretti C, Tripathy D, Petris G, Anderson EN, Migazzi A, Tosatto L, Cereseto A, Battaglioli E, Sorarù G, Lim WF, Rinaldi C, Sambataro F, Pourshafie N, Grunseich C, Romanel A, Pandey UB, Contestabile A, Ronzitti G, Basso M*, Pennuto M*. LSD1/PRMT6-targeting gene therapy to attenuate androgen receptor toxic gain-of-function ameliorates spinobulbar muscular atrophy phenotypes in flies and mice. Nat Commun. 2023 Feb 6;14(1):603. doi: 10.1038/s41467-023-36186-9. PMID: 36746939; PMCID: PMC9902531. (*co-corresponding). 

Pasetto L, Callegaro S, Corbelli A, Fiordaliso F, Ferrara D, Brunelli L, Sestito G, Pastorelli R, Bianchi E, Cretich M, Chiari M, Potrich C, Moglia C, Corbo M, Sorarù G, Lunetta C, Calvo A, Chiò A, Mora G, Pennuto M, Quattrone A, Rinaldi F, D’Agostino VG, Basso M#, Bonetto V#. Decoding distinctive features of plasma extracellular vesicles in amyotrophic lateral sclerosis. # Co-last and co-corresponding author. Molecular Neurodegeneration. 16, 52 (2021). https://doi.org/10.1186/s13024-021-00470-3. . (*co-last).

Migazzi A, Scaramuzzino C, Andreson N, Tripathy D, Hernandez I, Grant, Roccuzzo M, Tosatto L, Virlogeux A, Zuccato C, Caricasole A, Ratovitski T, Ross C, Pandey U, Saudou F, Pennuto M, Basso M. Huntingtin-Mediated axonal transport requires arginine methylation by PRMT6. Cell Reports, Volume 35, Issue 2, 108980, 2021.

Tripathy D, Migazzi A, Costa F, Roncador A, Gatto P, Fusco F, Boeri L, Albani D, Juárez-Hernández JL, Musio C, Colombo L, Salmona M, Wilhelmus MMM, Drukarch B, Pennuto M, Basso M. Increased Transcription of Transglutaminase 1 Mediates Neuronal Death in in Vitro Models of Neuronal Stress and Aβ1-42-mediated Toxicity. Neurobiol Dis. 2020 Jul;140:104849. doi: 10.1016/j.nbd.2020.104849. Epub 2020 Mar 25.

Basso M, Chen HH, Tripathy D, Conte M, Apperley KYP, De Simone A, Keillor JW, Ratan R, Nebbioso A, Sarno F, Altucci L, Milelli A. Designing Dual Transglutaminase 2/Histone Deacetylase Inhibitors Effective at Halting Neuronal Death. ChemMedChem. Feb 6;13(3):227-230, 2018. doi: 10.1002/cmdc.201700601.

Tripathy D; Vignoli B; Ramesh N; Polanco MJ; Coutelier M; Stephen CD; Canossa M; Monin ML; Aeschlimann P; Turberville S; Aeschlimann D; Schmahmann JD; Hadjivassiliou M; Durr A; Pandey UB; Pennuto M; Basso M. Mutations in TGM6 induce the unfolded protein response in SCA35. Human Molecular Genetics;26(19):3749-3762, 2017. doi: 10.1093/hmg/ddx259.

Basso M*, Pozzi S*, Tortarolo M, Fiordaliso F, Bisighini C, Pasetto L, Spaltro G, Lidonnici D, Gensano F, Battaglia E, Bendotti C, Bonetto V. Mutant copper-zinc superoxide dismutase (SOD1) induces protein secretion pathway alterations and exosome release in astrocytes: implications for disease spreading and motor neuron pathology in amyotrophic lateral sclerosis. The Journal of biological chemistry 288(22): 15699-15711, 2013. (*first-name co-authorship).

Basso M#, Berlin J, Xia L, Sleiman SF, Ko B, Haskew-Layton R, Kim E, Antonyak MA, Cerione RA, Iismaa SE, Willis D, Cho S, Ratan RR#. Transglutaminase inhibition protects against oxidative stress-induced neuronal death downstream of pathological ERK activation. The Journal of neuroscience : the official journal of the Society for Neuroscience 32:6561-6569, 2012. doi: 10.1523/JNEUROSCI.3353-11.2012 (# co-corresponding authorship).

McConoughey SJ*, Basso M*#, Niatsetskaya ZV, Sleiman SF, Smirnova NA, Langley BC, Mahishi L, Cooper AJ, Antonyak MA, Cerione RA, Li B, Starkov A, Chaturvedi RK, Beal MF, Coppola G, Geschwind DH, Ryu H, Xia L, Iismaa SE, Pallos J, Pasternack R, Hils M, Fan J, Raymond LA, Marsh JL, Thompson LM, Ratan RR. Inhibition of transglutaminase 2 mitigates transcriptional dysregulation in models of Huntington disease. EMBO molecular medicine 2:349-370, 2010. doi: 10.1002/emmm.201000084. (*first-name co-authorship; # co-corresponding authorship).