Pierre De Rossi PhD Neuroscience

Course and current status

12/2018 - today

Research associate in the Polymenidou group

University of Zurich

Zurich, Switzerland

Aim: Development of new models to study ALS and FTLD pathogenesis in vitro and in vivo

 

06/2014 – 11/2018

Post-doctoral Scholar in the Thinakaran lab

the University of Chicago

Chicago, IL, USA

Aim1: BIN1 physiological roles in the brain in myelination process and synaptic plasticity, learning and memory.

Aim2: BIN1 pathological implication in Amyloid pathology and/or Tau pathology 

 

01/2014 – 06/2014

Post-doctoral Fellow

Lyon Neuroscience Research Center

ONCOFLAM team (Neuro-oncology and neuro-inflammation)

Lyon, France

Aim: Elucidate the impact of auto-antibodies (limbic encephalitis) in synaptic remodeling, receptors internalization and trafficking and signaling pathway implicated.

 

Scientific summary

I am a neuroscientist specialized in cellular and molecular neurobiology. My goal is to develop a research team focusing on early mechanisms involved in neurodegenerative diseases and to explore possible common mechanism in neurodegeneration.

During my Ph.D., I studied the regulation of synaptic plasticity and synaptogenesis by VEGF, a vascular growth factor, and its consequences on learning and memory. I demonstrated that VEGF/VEGFR2 regulates NMDAR and AMPAR synaptic localization and increases the number of synaptic sites when coupled with synaptic activity. Moreover, I found that VEGF/VEGFR2 signaling at the synapse can trigger specific pathways implicated in learning and memory, and that the deletion of VEGFR2 in animal models decreased learning capacities (De Rossi et al, 2016). After my Ph.D., I spent 6 months studying the effects of autoantibodies, implicated in limbic encephalitis, on the synaptic homeostasis and signaling pathway regulation. I studied the effects of NMDAR antibodies on hippocampal functions (Mikasova et al, 2012) and mGluR1 antibodies role in cerebellar ataxia.

In 2014, I joined Prof. Gopal Thinakaran's lab at the University of Chicago to perform research in the cellular biology of Alzheimer disease. My project focused on BIN1, a recently identified gene as a major genetic risk factor for late-onset Alzheimer’s disease. It was important to first characterize BIN1 expression and localization pattern in the brain, as comprehensive studies were lacking on the subject (De Rossi et al, 2016, De Rossi et al, 2017). Next, I aimed to investigate a unique profile of BIN1 aggregation within the amyloid deposits in several mouse models of Alzheimer’s disease (De Rossi et al, 2018, Andrew et al, 2019). My work used complementary approaches of cellular biology (cell culture, transfection, trafficking and microscopy), molecular biology (plasmid design for in vitro interaction binding experiment and antibodies development) and animal models (behavior, IHC, IHF and biochemistry). Over the years, I have acquired experience in different microscopy techniques including STORM microscopy, 3D STED and confocal microscopy and I have experience in electron microscopy analyses. My last project uncovered the presynaptic localization of BIN1 at excitatory synapses and highlighted a new role for BIN1 in presynaptic release of glutamate and learning and memory (De Rossi et al, 2020). Before leaving the University of Chicago, I was finalizing a study demonstrating a role for BIN1 in the regulation of oligodendrocytes cytoskeleton organization and oligodendrocytes maturation (on-going studies in the Thinakaran lab). I was funded by the Alzheimer’s Association and the Brightfocus Foundation to explore the role of BIN1 in the seeding and propagation of Tau pathology in the brain (on-going studies in the Thinakaran lab).

In December 2018, I joined the Department of Quantitative BioMedicine (DQBM) at the University of Zurich (UZH). Here, 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.

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