Stem Cell Biology and Pharmacology of Neurodegenerative Diseases
The laboratory of Stem Cell Biology and Pharmacology of Neurodegenerative Diseases, led by Prof. Elena Cattaneo, is part of the Department of Bioscience at the University of Milan. The lab has relocated in INGM in July 2015, on the basis of a collaborative agreement between the University of Milan and INGM.
The laboratory studies Huntington’s Disease (HD), a rare genetic and neurodegenerative disease. The goal is to understand the physiopathology of this disease, in order to develop pharmacological, genetic and cellular strategies that could slow down the course of the illness or prevent its onset.
Currently, the laboratory is pursuing the following strategies:
- Investigate Huntingtin function in adulthood and throughout evolution (collaboration with Bioinformatic Unit – Dr Riccardo Rossi).
- Define the transcriptional profile of the developing human ventral telencephalon (giving rise to the striatum) at the single cell level to uncover regional/cell type-specific and time controlled expression of coding and non-coding transcripts that are involved in striatal differentiation in healthy and HD individuals (collaboration with Prof. Pagani’s Group);
- Investigate the differentiation potential of human pluripotent stem cells carrying the mutant Huntingtin to pinpoint the pathophysiological mechanisms underlying HD.
- Establish new high throughput screening methods to characterize cell identity during in vitro differentiation of human pluripotent stem cells to authentic striatal neurons, in order to optimize our striatal differentiation protocols.
The laboratory works with Huntington’s disease clinical experts in Italy and abroad, to assess the diagnostic and therapeutic potential of our research findings for clinical translation and application.
The laboratory is composed of one full professor, one associate professor, one university researcher, Post-Docs, PhD Students, Junior Fellows and Master Students, all of them are part of the University of Milan.
- Molecular Profiling of the developing human striatum.
- Optimization of striatal differentiation protocols using human pluripotent stem cells.
- Pathogenic mechanisms in Huntington’s Disease.
- Huntingtin function in adulthood and throughout evolution.
- Cholesterol delivery in the HD brain.
Elena Cattaneo has published >160 papers in peer-reviewed journals (including Science, Nature, Nature Genetics, Nature Neuroscience, Journal of Neuroscience, JBC). Her H-index is 54.
Selection of the 20 most relevant peer-reviewed publications (from 2000):
- Inhibiting pathologically active ADAM10 rescues synaptic and cognitive decline in Huntington’s Disease
Vezzoli E, Caron I, Talpo F, Besusso D, Conforti P, Battaglia E, Sogne E, Falqui A, Petricca L, Verani M, Martufi P, Caricasole A, Bresciani A, Cecchetti O, Rivetti di Val Cervo P, Sancini G, Riess O, Nguyen H, Seipold L, Saftig P, Biella G, Cattaneo and Zuccato C.
Journal of Clinical Investigation 2019 May 6; 130. pii: 120616. doi: 10.1172/JCI120616. [in press]
- Differentiation of human telencephalic progenitor cells into MSNs by inducible expression of Gsx2 and Ebf1.
Faedo A, Laporta A, Segnali A, Galimberti M, Besusso D, Cesana E, Belloli S, Moresco RM, Tropiano M, Fuca E, Wild S, Bosio A, Vercelli AE, Biella G, Cattaneo E.
Proc Natl Acad Sci U S A (2017) 114:E1234-E1242
- Cholesterol-loaded nanoparticles ameliorate synaptic and cognitive function in Huntington’s disease mice.
Valenza M, Chen JY, Di Paolo E, Ruozi B, Belletti D, Ferrari Bardile C, Leoni V, Caccia C, Brilli E, Di Donato S, Boido MM, Vercelli A, Vandelli MA, Forni F, Cepeda C, Levine MS, Tosi G, Cattaneo E.
EMBO Mol Med (2015) 7:1547-64
- Mutant Huntingtin promotes autonomous microglia activation via myeloid lineage-determining factors.
Crotti A, Benner C, Kerman BE, Gosselin D, Lagier-Tourenne C, Zuccato C, Cattaneo E, Gage FH, Cleveland DW, Glass CK.
Nat Neurosci (2014) 17:513-21
- Molecular and functional definition of the developing human striatum.
Onorati M, Castiglioni V, Biasci D, Cesana E, Menon R, Vuono R, Talpo F, Laguna Goya R, Lyons PA, Bulfamante GP, Muzio L, Martino G, Toselli M, Farina C, Barker RA, Biella G, Cattaneo E.
Nat Neurosci (2014) 17:1804-15
- Developmentally coordinated extrinsic signals drive human pluripotent stem cell differentiation toward authentic DARPP-32+ medium-sized spiny neurons.
Delli Carri A, Onorati M, Lelos MJ, Castiglioni V, Faedo A, Menon R, Camnasio S, Vuono R, Spaiardi P, Talpo F, Toselli M, Martino G, Barker RA, Dunnett SB, Biella G, Cattaneo E.
Development (2013) 140:301-12
- An evolutionary recent neuroepithelial cell adhesion function of huntingtin implicates ADAM10-Ncadherin.
Lo Sardo V, Zuccato C, Gaudenzi G, Vitali B, Ramos C, Tartari M, Myre MA, Walker JA, Pistocchi A, Conti L, Valenza M, Drung B, Schmidt B, Gusella J, Zeitlin S, Cotelli F, Cattaneo E.
Nat Neurosci (2012) 15:713-21
- Neural stem cell systems: physiological players or in vitro entities?
Conti L, Cattaneo E.
Nat Rev Neurosci (2010) 11:176-87
- Cholesterol defect is marked across multiple rodent models of Huntington’s disease and is manifest in astrocytes.
Valenza M, Leoni V, Karasinska JM, Petricca L, Fan J, Carroll J, Pouladi MA, Fossale E, Nguyen HP, Riess O, MacDonald M, Wellington C, DiDonato S, Hayden M, Cattaneo E.
J Neurosci (2010) 30:10844-50
- Molecular mechanisms and potential therapeutical targets in Huntington’s disease.
Zuccato C, Valenza M, Cattaneo E.
Physiol Rev (2010) 90:905-81
- Brain-derived neurotrophic factor in neurodegenerative diseases.
Zuccato C, Cattaneo E.
Nat Rev Neurol (2009) 5:311-22
- Phylogenetic comparison of huntingtin homologues reveals the appearance of a primitive polyQ in sea urchin.
Tartari M, Gissi C, Lo Sardo V, Zuccato C, Picardi E, Pesole G, Cattaneo E.
Mol Biol Evol (2008) 25:330-8
- Widespread disruption of repressor element-1 silencing transcription factor/neuron-restrictive silencer factor occupancy at its target genes in Huntington’s disease.
Zuccato C, Belyaev N, Conforti P, Ooi L, Tartari M, Papadimou E, MacDonald M, Fossale E, Zeitlin S, Buckley N, Cattaneo E.
J Neurosci (2007) 27:6972-83
- Normal huntingtin function: an alternative approach to Huntington’s disease.
Cattaneo E, Zuccato C, Tartari M.
Nat Rev Neurosci (2005) 6:919-30
- Dysfunction of the cholesterol biosynthetic pathway in Huntington’s disease.
Valenza M, Rigamonti D, Goffredo D, Zuccato C, Fenu S, Jamot L, Strand A, Tarditi A, Woodman B, Racchi M, Mariotti C, Di Donato S, Corsini A, Bates G, Pruss R, Olson JM, Sipione S, Tartari M, Cattaneo E.
J Neurosci (2005) 25:9932-9
- Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes.
Zuccato C, Tartari M, Crotti A, Goffredo D, Valenza M, Conti L, Cataudella T, Leavitt BR, Hayden MR, Timmusk T, Rigamonti D, Cattaneo E.
Nat Genet (2003) 35:76-83
- Opinion: neural stem cell therapy for neurological diseases: dreams and reality.
Rossi F, Cattaneo E.
Nat Rev Neurosci (2002) 3:401-9
- Loss of normal huntingtin function: new developments in Huntington’s disease research.
Cattaneo E, Rigamonti D, Goffredo D, Zuccato C, Squitieri F, Sipione S.
Trends Neurosci (2001) 24:182-8
- Shc signaling in differentiating neural progenitor cells.
Conti L, Sipione S, Magrassi L, Bonfanti L, Rigamonti D, Pettirossi V, Peschanski M, Haddad B, Pelicci P, Milanesi G, Pelicci G, Cattaneo E.
Nat Neurosci (2001) 4:579-86
- Loss of huntingtin-mediated BDNF gene transcription in Huntington’s disease.
Zuccato C, Ciammola A, Rigamonti D, Leavitt BR, Goffredo D, Conti L, MacDonald ME, Friedlander RM, Silani V, Hayden MR, Timmusk T, Sipione S, Cattaneo E.
Science (2001) 293:493-8