Pierre De Rossi

Pierre De Rossi
University of Zurich | UZH · Department of Quantitative BioMedicine

PhD

About

41
Publications
5,430
Reads
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609
Citations
Introduction
I am working with Prof. Magdalini Polymenidou on developing a new mouse model to decipher cellular mechanisms of TDP-43 associated pathologies [Amyotrophic Lateral Sclerosis (ALS) and frontotemporal lobar degeneration (FTLD)]. My work is using iPSC-derived human neuronal culture, compartmentalized culture and inoculated mouse models. I have recently been awarded the career development award from the Synapsis foundation.
Additional affiliations
December 2018 - present
University of Zurich
Position
  • Research Associate
July 2014 - November 2018
University of Chicago
Position
  • PostDoc Position
January 2014 - June 2014
Lyon Neuroscience Research Center
Position
  • PostDoc Position
Description
  • Aim: elucidate the impact of auto-antibodies (limbic encephalitis) in synaptic remodeling, receptors internalization and trafficking and signaling pathway implicated. (AntiNMDAR and AntimGluR1)
Education
September 2010 - December 2013
Claude Bernard University Lyon 1
Field of study
  • Neuroscience and neurobiology
September 2008 - June 2010
Claude Bernard University Lyon 1
Field of study
  • Physiology and Neuroscience
September 2004 - June 2008
University of Nantes
Field of study
  • Biology and Biochemistry, Cellular biology and Physiology

Publications

Publications (41)
Preprint
Aggregation of the RNA-binding protein TDP-43 is the main common neuropathological feature of TDP-43 proteinopathies. In physiological conditions, TDP-43 is predominantly nuclear and contained in biomolecular condensates formed via liquid-liquid phase separation (LLPS). However, in disease, TDP-43 is depleted from these compartments and forms cytop...
Preprint
Full-text available
Hexanucleotide G 4 C 2 repeat expansions in the C9ORF72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Dipeptide repeat proteins (DPRs) generated by translation of repeat-containing RNAs show toxic effects in vivo as well as in vitro and are key targets for therapeutic intervention....
Article
Full-text available
Morphologically distinct TDP-43 aggregates occur in clinically different FTLD-TDP subtypes, yet the mechanism of their emergence and contribution to clinical heterogeneity are poorly understood. Several lines of evidence suggest that pathological TDP-43 follows a prion-like cascade, but the molecular determinants of this process remain unknown. We...
Article
Full-text available
While the initial pathology of Parkinson's disease and other α-synucleinopathies is often confined to circumscribed brain regions, it can spread and progressively affect adjacent and distant brain locales. This process may be controlled by cellular receptors of α-synuclein fibrils, one of which was proposed to be the LAG3 immune checkpoint molecule...
Article
Full-text available
Gene mutations causing cytoplasmic mislocalization of the RNA-binding protein FUS lead to severe forms of amyotrophic lateral sclerosis (ALS). Cytoplasmic accumulation of FUS is also observed in other diseases, with unknown consequences. Here, we show that cytoplasmic mislocalization of FUS drives behavioral abnormalities in knock-in mice, includin...
Article
Full-text available
Mutations disrupting the nuclear localization of the RNA-binding protein FUS characterize a subset of amyotrophic lateral sclerosis patients (ALS-FUS). FUS regulates nuclear RNAs, but its role at the synapse is poorly understood. Using super-resolution imaging we determined that the localization of FUS within synapses occurs predominantly near the...
Preprint
Full-text available
While the initial pathology of Parkinson's disease and other α-synucleinopathies is often confined to circumscribed brain regions, it can spread and progressively affect adjacent and distant brain locales. This process may be controlled by cellular receptors of α-synuclein fibrils, one of which was proposed to be the LAG3 immune checkpoint molecule...
Preprint
Full-text available
While the initial pathology of Parkinson’s disease and other α-synucleinopathies is often confined to circumscribed brain regions, it can spread and progressively affect adjacent and distant brain locales. This process may be controlled by cellular receptors of α-synuclein fibrils, one of which was proposed to be the LAG3 immune checkpoint molecule...
Article
Protein aggregation is the main hallmark of neurodegenerative diseases. Many proteins found in pathological inclusions are known to undergo liquid-liquid phase separation, a reversible process of molecular self-assembly. Emerging evidence supports the hypothesis that aberrant phase separation behavior may serve as a trigger of protein aggregation i...
Article
Gene mutations causing cytoplasmic mislocalization of the RNA-binding protein FUS, lead to severe forms of amyotrophic lateral sclerosis (ALS). Cytoplasmic accumulation of FUS is also observed in other diseases, with unknown consequences. Here, we show that cytoplasmic mislocalization of FUS drives behavioral abnormalities in knock-in mice, includi...
Preprint
Full-text available
FUS is a primarily nuclear RNA-binding protein with important roles in RNA processing and transport. FUS mutations disrupting its nuclear localization characterize a subset of amyotrophic lateral sclerosis (ALS-FUS) patients, through an unidentified pathological mechanism. FUS regulates nuclear RNAs, but its role at the synapse is poorly understood...
Preprint
Full-text available
Gene mutations causing cytoplasmic mislocalization of the RNA-binding protein FUS, lead to severe forms of amyotrophic lateral sclerosis (ALS). Cytoplasmic accumulation of FUS is also observed in other diseases, with unknown consequences. Here, we show that cytoplasmic mislocalization of FUS drives behavioral abnormalities in knock-in mice, includi...
Article
Full-text available
FUS is a primarily nuclear RNA-binding protein with important roles in RNA processing and transport. FUS mutations disrupting its nuclear localization characterize a subset of amyotrophic lateral sclerosis (ALS-FUS) patients, through an unidentified pathological mechanism. FUS regulates nuclear RNAs, but its role at the synapse is poorly understood...
Article
Full-text available
BIN1, a member of the BAR adaptor protein family, is a significant late-onset Alzheimer disease risk factor. Here, we investigate BIN1 function in the brain using conditional knockout (cKO) models. Loss of neuronal Bin1 expression results in the select impairment of spatial learning and memory. Examination of hippocampal CA1 excitatory synapses rev...
Article
Full-text available
Alzheimer's disease (AD) is pathologically characterized by the deposition of the β-amyloid (Aβ) peptide in senile plaques in the brain, leading to neuronal dysfunction and eventual decline in cognitive function. Genome-wide association studies have identified the bridging integrator 1 (BIN1) gene within the second most significant susceptibility l...
Article
Full-text available
BIN1, a member of the BAR adaptor protein family, is a significant late-onset Alzheimer disease risk factor. Here, we investigate BIN1 function in the brain using conditional knockout (cKO) models. Loss of neuronal Bin1 expression results in the select impairment of spatial learning and memory. Examination of hippocampal CA1 excitatory synapses rev...
Article
Full-text available
BIN1 is the most significant late‐onset Alzheimer's Disease (AD) susceptibility locus identified via genome‐wide association studies. BIN1 is an adaptor protein that regulates membrane dynamics in the context of endocytosis and membrane remodeling. An increase in BIN1 expression and changes in the relative levels of alternatively‐spliced BIN1 isofo...
Poster
Full-text available
Background: BIN1 was identified as the second most prevalent risk factor for late-onset Alzheimer’s disease (AD) in genome-wide association studies. A reduction in neuronal BIN1 isoform has been reported in patients with AD. Though little is known about BIN1 function in the brain, the loss of BIN1 expression has been proposed to influence BACE1 tra...
Poster
Full-text available
Background: BIN1 was identified as the second most prevalent risk factor for late-onset Alzheimer’s disease (AD) in genome-wide association studies. A reduction in neuronal BIN1 isoform has been reported in patients with AD. Though little is known about BIN1 function in the brain, the loss of BIN1 expression has been proposed to influence BACE1 tra...
Poster
Full-text available
Background: The deposition of amyloid-β (Aβ) peptide in extracellular senile plaques is a hallmark of Alzheimer’s disease (AD). Aβ is derived from the cleavage of amyloid precursor protein (APP) by the β- and γ - secretases. It has been proposed as the key trigger in the complex cascade of events which lead to AD. Genome-wide association studies h...
Article
Full-text available
Alzheimer’s disease (AD) is a devastating neurodegenerative disorder characterized by pathological brain lesions and a decline in cognitive function. β-Amyloid peptides (Aβ), derived from proteolytic processing of amyloid precursor protein (APP), play a central role in AD pathogenesis. β-Site APP cleaving enzyme 1 (BACE1), the transmembrane asparty...
Article
Full-text available
BIN1 is the second most significant Alzheimer's disease (AD) risk factor gene identified through genome-wide association studies. BIN1 is an adaptor protein that can bind to several proteins including c-Myc, clathrin, adaptor protein-2 and dynamin.BIN1is widely expressed in the brain and peripheral tissue as ubiquitous and tissue-specific alternati...
Poster
Full-text available
Accumulation of BACE1 in dystrophic neurites surrounding amyloid deposits is a shared pathological feature in human Alzheimer's disease (AD) and transgenic mouse models. Several hypotheses have been proposed to explain the amyloid deposit-associated increase in BACE1 levels, and how this presynaptic elevation of BACE1 might contribute to amyloid pr...
Article
Full-text available
Background: Genome-wide association studies have identified BIN1 within the second most significant susceptibility locus in late-onset Alzheimer's disease (AD). BIN1 undergoes complex alternative splicing to generate multiple isoforms with diverse functions in multiple cellular processes including endocytosis and membrane remodeling. An increase i...
Article
Full-text available
Vascular endothelial growth factor (VEGF) is known to be required for the action of antidepressant therapies but its impact on brain synaptic function is poorly characterized. Using a combination of electrophysiological, single-molecule imaging and conditional transgenic approaches, we identified the molecular basis of the VEGF effect on synaptic t...
Article
Full-text available
The vascular endothelial growth factor (VEGF) plays a critical role during vascular development but recent evidence indicates that it also regulates various neuronal processes in the nervous system, such as neurogenesis, hippocampal synaptic plasticity, learning and memory. Recently, we showed a novel interaction between the glutamate receptor NMDA...
Poster
Full-text available
The vascular endothelial growth factor (VEGF) is well known to play a critical role during vascular development but recent evidence indicates that it also regulates key neuronal processes in the nervous system, such as neurogenesis, hippocampal synaptic plasticity, learning and memory. However, little is known about the underlying molecular mechani...
Poster
Full-text available
The vascular endothelial growth factor (VEGF) is well known to play a critical role during vascular development but recent evidence indicates that VEGF has also direct effects on neurons, regulating among other processes hippocampal synaptic transmission and plasticity. Little is known about the underlying molecular mechanisms involved in the VEGF-...
Article
Full-text available
Autoimmune synaptic encephalitides are recently described human brain diseases leading to psychiatric and neurological syndromes through inappropriate brain-autoantibody interactions. The most frequent synaptic autoimmune encephalitis is associated with autoantibodies against extracellular domains of the glutamatergic N-methyl-d-aspartate receptor,...
Article
Full-text available
NMDA type glutamate receptors (NMDARs) are best known for their role in synaptogenesis and synaptic plasticity. Much less is known about their developmental role before neurons form synapses. We report here that VEGF, which promotes migration of granule cells (GCs) during postnatal cerebellar development, enhances NMDAR-mediated currents and Ca(2+)...