Physiopathology of neural stem cells

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Group leader:  Annalisa Buffo 

Physiopathology of neural stem cells


Air pollution and Multiple Sclerosis: effects of the exposure to particulate matter (PM) on neuroinflammation and myelin repair.
2021-2023 | Cassa di Risparmio di Torino (CRT) Foundation

Enrica Boda, PI

In this project we will study the mechanisms underlying the negative effects of exposure to environmental particulate matter (PM) in myelin repair ( Air pollution and Multiple Sclerosis ) and the higher vulnerability to PM of subjects primed to develop autoimmunity against myelin.

SPACER: a single cell SPAtiotemporal transcriptomic atlas to unveil CERebellar development and function in mouse
2021-2022 | EASI Genomics 3 rd call for Proposals for Transnational Access Projects 2021

A. Buffo, V. Cerrato

Thanks to this support, our researchers will perform in situ gene expression analyses on rodent tissues at distinct developmental stages before and after birth. In this way, we will study the molecular processes underneath the generation and physiology of cerebellar cells, aiming at fully clarifying the mechanisms of functioning and misfunctioning of this brain area. The experiments funded by EASI Genomics will be performed in Stockholm, in a prestigious facility partner of the consortium, named SciLife Lab. 
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Pilot Project: Air pollution and Multiple Sclerosis: role of particulate matter (PM) exposure and associated extracellular vesicle trafficking in neuroinflammation and demyelination.
2020-2021 | Italian Multiple Sclerosis Foundation (FISM) 

Enrica Boda, PI
Research network: Valentina Bollati, Antonello Rigamonti (University of Milan)

In this project, we will investigate the role of particulate matter exposure as risk factor for the onset and progression of Multiple Sclerosis and the undelying cellular mechanisms

Novel Strategies for Cell-based Neural Reconstruction - NSC-Reconstruct
2020-2024 | H2020-SC1-BHC-2018-2020

Research network: Elena Cattaneo, Coordinator (University of Milano), Malin Parmar (University of Lund), Oliver Bruestle  (UniversitaetsKlinikum Bonn), Ernest Arenas (Karolinska Institutet), Roger Barker (University of Cambridge), Agnete Kirkeby (Kobenhavns Universitet), Meng Li (Cardiff University),  Magdalena Goetz (Helmholtz Zentrum Muenchen), Pierre Vanderhaeghen (VIB-KULeuven Center) , Andreas Bosio (Miltenyi Biotec GMBH), Simone Haupt (Life and Brain GMBH), Carlos Villaescusas (Novo Nordisk).

In this project we will be leading WP3 and specifically aim at developing innovative therapeutic approaches for Huntington Disease (HD) based on the transplantation of human stem cell derivatives in preclinical models of HD and on training protocols to favour the integration of the transplanted cells. Further, we will implement strategies of in situ reprogramming to obtain striatal neurons from glial cells, and investigate the mechanisms regulating reactivity and activation of a neurogenic potential in astrocytes.

Oligodendrocyte Precursor Cells for Myelin Repair and Gliomagenesis
2019-2021 | Progetti di ricerca ex-post di Ateneo (University of Torino and Compagnia di San Paolo)

A.Buffo, E. Boda

This project was conceived as part of an european ITN-ETN grant application coordinated by Fernando de Castro, Cajal Institute, Madrid. In this frame, this local funding supports our studies on the functional heterogeneity of oligodendrocyte precursor cells in response to DNA damage and oxidative stress which occur in multiple CNS pathologies and dysfunctions, from Multiple Sclerosis to chemotherapy.

Allele-specific siRNAs as therapeutic option for ADLD: in vitro pre-clinical validation on unique human experimental models
2020-2022 | ELA International, Luxembourg

Research network: E. Giorgio and A. Brusco (University of Torino), S Goldman (University of Rochester, USA).

In this project we will generate two innovative glial in vitro disease models based on induced pluripotent stem cells (iPSC) derived from ADLD (Autosomal Dominant leukodystrophy with autonomic disease) patients that will allow validating our therapeutic strategy based on Allele Specific Silencing. Our project is intended to pave the way towards a therapy for ADLD and also establish distinctive human ADLD-relevant models and therapeutic approaches that may have great importance for future studies non only on ADLD but also on the physiopathology and therapy of other leukodystrophies and genetic diseases.

Driving microglia metabolism toward remyelination and restoration of brain damage in MS  
2015-2018 | Merck Serono/Grant for Multiple Sclerosis Innovation

Annalisa Buffo, head of research unit
Research network: coordinator Claudia Verderio, Neuroscience Institute (IN) of CNR, Marta Fumagalli, University of Milan, Pierre Gressens, Inserm, Paris; Peter Cameliet, Vesalius Research CentreLeuven; Antonio Uccelli, University of Genoa

This project aims at defining the metabolic signatures that define a pro-regenerative microglial phenotype as expressed by extracellular-vescicle-mediated enhancement of remyelination by rodent oligodendrocyte progenitor cells. The ultimate goal of this research is to modulate the phenotype of human microglia so that microglia can foster myelin repair. We contribute our specific expertise in oligodendrocyte progenitors and mouse models of Multiple Sclerosis and examine how delivery of microglia-derived extracellular vescicle to the brain of mouse models affects oligodendrocyte progenitors and remyelination in vivo.

Characterization of a novel microRNA involved in myelination: a new potential pathogenetic mechanisms in multiple sclerosis
2015-2017 | Cariplo Foundation - Biomedical Research conducted by Young Researchers

Enrica Boda, head of reseach unit; Davide Lecca, University of Milan, coordinator

This project aims at elucidating the role of a novel family of miRNAs in the regulation of oligodendroglial differentiation and in the pathogenesis of Multiple Sclerosis.

Influence of maternal behaviour on the expression of brain plasticity brakes: a role in the susceptibility to anxiety?
2015-2017 | Research Project, University of Turin - Compagnia di San Paolo

Daniela Carulli co-PI with Carola Eva, NICO

This project aims at elucidating whether maternal care affects chemical/physical features of perineuronal nets in the limbic system thereby influencing neuronal communication within specific networks and, in turn, anxiety in the adult.

Neurostemcellrepair - European stem cell consortium for neural cell replacement, reprogramming and functional brain repair
2013-2017 | FP7 European Union

E Fucà, A Buffo, D Carulli participating in the research unit headed by A Vercelli;
Research network: Elena Cattaneo, University of Milan, coordinator, Ernest Arenas, Karoliska Institute, deputy coordinator, Parmar Malin, University of Lund, Stephen Dunnet, University of Cardiff, Oliver Brustle, University of Bonn, Roger Barker, University of Cambridge, Charles ffrench-Constant, University of Edimburgh, Andreas Bosio, Milteny, Ida Biunno, Isenet).

This project aims at developing new strategies for stem cell therapies in Hungtington and Parkinson diseases, including acquisition of specific neuronal identities and functional integration in the recipient brain. We contribute our expertise in rodent models of Hungtington disease, and analyse how specific training activities can ameliorate differentiation and integration of grafted cells.
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Determinants of neuronal degeneration in Ataxia-Telangiectasia
2014-2017 | Telethon Foundation

Project PIs: Domenico Delia, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, and Lorenzo Magrassi, Dipartimento di Scienze Clinico-Chirurgiche, Diagnostiche e Pediatriche, University of Pavia. Annalisa Buffo and Giulia Nato take part in the project as external collaborators.

This project aims at unveiling the functional defects that determine malfunctioning and neurodegeneration in the cerebellum of patients suffering from Ataxia-Telangiectasia. To reach this goal we study how neuronal cells obtained from the fibroblasts of patients and healthy controls mature, survive and function.

Endogenous sources of stem cells/ neural progenitors for CNS repair

2014-September 2016 | Fondazione CRT

Annalisa Buffo co-proponent with Luca Bonfanti and Paolo Peretto, NICO

This project aims at investigating the physiology of parenchymal progenitors and their gliogenic and neurogenic responses upon lesion. Based on our specific expertise, we investigate dedifferentiation/reprogramming in reactive astrocytes and the properties of oligodendrocyte progenitors.

Targeting oligodendrocyte progenitor cell division mode to improve myelin repair in the aging CNS
2014-2015 | Fondazione Umberto Veronesi - Postdoctoral Fellowship Program, Enrica Boda

Myelin is a lipid-rich ensheathment produced by specialized cells called oligodendrocytes, that enwrap neuronal axons and allow the fast conduction of nervous signals. Myelin damage causes very serious pathologies characterized by motor and cognitive symptoms. In the human brain, aging is associated with the loss of myelin, reduced oligodendrocyte production and delayed remyelination in case of insults or pathology.
This is at least in part due to molecular alterations in oligodendrocyte progenitors, that affect their division modality and regenerative/reparative functions. The identification of these molecular mechanisms is highly relevant for the comprehension of the OPC biology and age-related functional decline, and can set the basis for new therapeutical approaches aimed at improving adult oligodendrogenesis and eventually ameliorate myelin integrity and repair at old ages.
This knowledge may be also applied to the study and treatment of human neurodegenerative diseases.

Complex mechanisms underlying permanent effects of the perinatal environment on neural plasticity and vulnerability to psychopathology
2014-2015 | Fondazione CRT

D. Carulli and A. Buffo: co-PI with Carola Eva, NICO

This project aims at investigating whether maternal care has an impact on the development of perineuronal nets and myelin in the limbic system, in parallel with an alteration of emotional behavior of adult mice.

Effect of substances of abuse, psychoactive drugs, stress and maternal care on brain development and vulnerability to psychopathology
2010-2012 | PRIN2010  Italian Ministry of University and Research, N. 20107MSMA4

A Buffo, head of Unit, participant: D Carulli; Giovanni Biggio, University of Cagliari, coordinator;
Marco Riva, University of Milan, Carola Eva, University of Turin, Paola Palanza, University of Parma, Nicoletta Brunello, University of Modena.

This project examines how perinatal adverse events, known to be associated with vulnerability to the onset of psychopathology and behaviour disorders, affect the normal progression of myelination and the deposition of plasticity brakes. We contribute our expertise on oligodendrocytes, myelin and perineuronal nets.