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Conference : Synaptic mechanisms of neurodegeneration and neuroprotection in Amyotrophic Lateral Sclerosis

Synaptic mechanisms of neurodegeneration and neuroprotection in Amyotrophic Lateral Sclerosis

25 février 2020,  12h à 13h30, amphithéâtre Babinski
Entrée libre et sans inscription

Francesco Roselli
guess : Maria-Grazia Biferi

In vivo electrophysiology and multiplexed chemogenetics demonstrate that, rather than hyperexcitation, ALS MNs experience postsynaptic disruptions and decreased synaptic responses. Synaptic restoration by cAMP/PKA improves disease pathobiochemistry stimulating MN firing, supporting a synaptic failure model for ALS.

 

biography

NAME: Francesco Roselli

POSITION TITLE: Principal Investigator

EDUCATION/TRAINING

INSTITUTION AND LOCATION

DEGREE

 

Completion Date

MM/YYYY

 

FIELD OF STUDY

 

Bari University-School of Medicine, Bari, Italy

MD

07/2001

Human Medicine

Bari University-Dept. of Neurology, Bari, Italy

Board Neurol.

 

10/2006

Neurology

Max-Planck Institute of Psychiatry and Bari University Natural Sciences Faculty

 

Friedrich Miescher Institute for Biomedical Research

PhD

 

 

Post-doc

03/2010

 

 

08/2014

Experimental Neurobiology

 

Neurodegeneration/

Motoneuron disease

 

Ulm University

Habilitation

12/2016

Neurology

 

  1. Personal Statement

Francesco Roselli is group leader in the neuroscience program of the Dept. of Neurology at the Ulm University and at the German Center for Neurodegenerative Diseases (DZNE)-Ulm. The Roselli group focuses on the exploration and manipulation of neuronal circuits and synaptic biology in acute and chronic neurodegenerative conditions, such as traumatic brain injury and ALS. The Roselli group exploits a set of in vivo approaches (anterograde and retrograde viral tools for the structural analysis of neuronal connectivity together with tissue clearing, confocal microscopy, STED microscopy and light-sheed microscopy) and in vitro approaches (including the study of iPSC-derived motoneurons and cerebral organoids). The Roselli group also exploits a number of chemiogenetic approaches to control the activity of neurons as well as specific signaling cascades in neuronal and non-neuronal cells.

  1. Positions and Honors
  2. Positions

2014-current Principal Investigator, Dept. of Neurology, Ulm University

2018-current Executive director, Neurozentrum Ulm University

2018-current Research groupleader, German Center for Neurodegenerative Diseases-Ulm

  1. Honors

2001                           Medal of Excellence, University of Bari

2006-2007                  Vigoni Fellowship (Conferenza dei Rettori delle Università Italiane, CRUI)           

2008-2010                  Max Planck Institute of Psychiatry (MPIP) fellowship

2011-2013                  European Molecular Biology Organization (EMBO) long-term fellowship          

  1. Contributions to science (10 recent, highly relevant publications)
  2. Ludolph AC, Dorst J, Dreyhaupt J, Weishaupt JH, Kassubek J, Weiland U, Meyer T, Petri S, Hermann A, Emmer A, Grosskreutz J, Grehl T, Zeller D, Boentert M, Schrank B, Prudlo J, Winkler AS, Gorbulev S, Roselli F, Schuster J, Dupuis L; LIPCAL-ALS Study Group. Effect of high-caloric nutrition on survival in

amyotrophic lateral sclerosis. Ann Neurol. 2019 Dec 17. doi: 10.1002/ana.25661.

  1. Catanese A, olde Heuvel F, Mulaw M, Demestre M, Higelin J, Barbi G, Freischmidt A, Weishaupt JH, Ludolph AC, Roselli F*, Boeckers TM*. Retinoic acid worsens ATG10-dependent autophagy impairment in TBK1-mutant hiPSC-derived motoneurons through SQSTM1/p62 accumulation. Autophagy, 2019 Oct;15(10):1719-1737. *co-senior authors
  2. Commisso B, Ding L, Varadi K, Gorges M, Bayer D, Boeckers TM, Ludolph AC, Kassubek J, Müller OJ, Roselli F. Stage-dependent remodeling of projections to motor cortex in ALS mouse model revealed by a new variant retrograde-AAV9. Elife. 2018 Aug 23;7.
  3. Catanese A, Garrido D, Walther P, *Roselli F, *Böckers TM. Nutrient limitation affects presynaptic structures through dissociable Bassoon autophagic degradation and impaired vesicle release. Journal Cereb Blood Flow Metab 2018 Jul 4:271678X18786356. *co-senior authors
  4. Chandrasekar A, olde Heuvel F, Tar L, Hageston AM, Palmer A, Linkus B, Ludolph AC, Huber-Lang M, Böckers TM, Bading H, Roselli F. Parvalbumin interneurons shape neuronal vulnerability in blunt TBI. Cerebral Cortex Jun 30. doi: 10.1093/cercor/bhy139
  5. Ouali Alami N, Schurr C, Olde Heuvel F, Tang L, Li Q, Tasdogan A, Kimbara A, Nettekoven M, Ottaviani G, Raposo C, Röver S, Rogers-Evans M, Rothenhäusler B, Ullmer C, Fingerle J, Grether U, Knuesel I, Boeckers TM, Ludolph A, Wirth T, *Roselli F, *Baumann B. NF-κB activation in astrocytes drives a stage-specific beneficial neuroimmunological response in ALS. EMBO J. 2018 Jun 6. pii: e98697. doi: 10.15252/embj.201798697. *co-senior authors News&Views commentary
  6. Martinez-Silva ML, Imhoff-Manuel RD, Sharma A, Heckman CJ, Shneider NA, Roselli F, Zytnicki D, Manuel M. Hypoexcitability precedes denervation in the large fast-contracting motor units in two unrelated mouse models of ALS. eLife. 2018 Mar 27;7. Insight commentary and cover story
  7. Vogl AM, Brockmann MM, Giusti SA, Maccarrone G, Vercelli CA, Bauder CA, Richter JS, Roselli F, Hafner AS, Dedic N, Wotjak CT, Vogt-Weisenhorn DM, Choquet D, Turck CW, Stein V, Deussing JM, Refojo D. Neddylation inhibition impairs spine development, destabilizes synapses and deteriorates cognition. Nat Neurosci. 2015 Feb;18(2):239-51 Nat Neurosci preview

9.Saxena S*, Roselli F*, Katyayani S,Leptien K, Julien JP, Gros-Louis F, Caroni P. Endogenous neuroprotection signaling through excitability and mTOR required in motoneurons to ameliorate disease process and extend survival in ALS mice. Neuron. 2013 Oct 2;80(1):80-96. *equal contribution  Neuron preview                    

  1. Roselli F, Tirard M, Lu J, Hutzler P, Lamberti P, Livrea P, Morabito M, Almeida OF. Soluble beta-amyloid1-40 induces NMDA-dependent degradation of postsynaptic density-95 at glutamatergic synapses. J Neurosci. 2005 Nov30;25(48):11061-70. JNeurosci highlight         
  1. Research Support

2020-2023    DFG- RO-5004/8-1, “Post-synaptic disruption drives motoneuron vulnerability and disease progression in ALS”                                                                                                        (210.000 €)

2020-2022    Fondation Thierry Latran, co-investigator (with Luc Dupuis), “Hypothalamic alterations as a cause of weight loss and clinical progression in ALS” (HypotALS)                                (125.000 €)

2019-2022    DFG-SFB1149/2 (renewed funding period-project B05) “Ethanol intoxication in TBI: mechanisms of neuroprotection and neuroglial modulation”                                                                (400.000 €)

2019-2020    Radala Foundation for ALS research Co-investigator (with Daniel Zytnicki), “Synaptically-driven neuroprotection in ALS”                                                                                           (200.000 CHF/2)

2019-2021    Fondation Thierry Latran, principal investigator, “Translational modulation of synaptic inputs to MN through PKA-coupled receptors: bringing excitation to the clinics” (TRiALS)            (100.000 €)

2017-2018    Investigator-Initiated Research (Grant4Application program) agreement with Bayer Ltd for the project “FGFR inhibitors in acute and subacute brain trauma”                                                           (55.000 €)

2017-2020    Principal Investigator in the ERANET-Neuron MICRONET consortium “Cortical microcircuitry after traumatic brain injury: molecules to networks”                                                        (150.000 €)

2015-2017    Research Agreement with Hoffmann-La Roche Ltd on the project “CB2 receptor-mediated neuroprotection in preclinical models of Amyotrophic Lateral Sclerosis”                          (52.000 €)

2015-2018    DFG-SFB1149 (project B05) “Ethanol intoxication as relevant comorbidity in Traumatic Brain Injury: innovative approaches to neuroprotection in TBI”                                                                          (373.500 €)

2015-2018    Baustein Program, “Chemogenetic exploration of neuroprotective pathways in motoneuron disease” University of Ulm                                                                                                                        (105.000 €)

2014-2016    Synapsis Foundation Grant “Chemogenetic approaches to investigate astrocyte role in Alzheimer´s Disease and ALS” (three years)                                                                              (210.000 CHF)

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