STÉPHANE BELIN

Technics

•     Ex-vivo and in-vivo model of injury
•     Molecular biology: PCR-qPCR, NGS...
•     Virus production and manipulation (AAV, lentivirus, rabies)
•     Cell biology: IF, 
•     Biochimistry:immunoprecipitation, western blot, labelling puromycin, Puro-PLA, proteomic
•     Cell culture: primary neurons, cell lines, explant, microfluidic 
•     Microscopy: live imaging, spinning disk, confocal, 3D

Teaching in Master 1 and Master 2 at Université Grenoble Alpes

·         Education and key qualifications

2023: Habilitation à Diriger des Recherches-HDR - Grenoble Alpes University- Ecole Doctorale Chimie Sciences du Vivant (France)

2020: Experimental surgery on rodent Grenoble Alpes University

2009: PhD in Molecular Biology at University of Lyon (France): role of ribosome biogenesis in cancer development (supervisor Dr. Jean-Jacques Diaz).

2008: DIU animal experimentation level 1 at Ecole Normal Superieur Lyon (France)

2005: Master degree in Functional Genetics and Oncology at University of Lyon (France)

·         Current position(s)

2018- present: Group Leader of the team Translation regulation in normal and pathological conditions at Grenoble Institute of Neuroscience GIN-INSERM U1216 (France). 7 articles, 3 reviews

2017-present: Assistant Professor CRCN INSERM at Grenoble Institute of Neuroscience INSERM U1216 (France).

·         Previous position(s)

2016-2017: Postdoctoral Fellow at Grenoble Institute of Neuroscience INSERM U1216 (France). Laboratory of Pr. Frederic Saudou Role of HTT in glaucoma and CNS injury. (1 award)

2010-2016: Postdoctoral Fellow in the department of Neurology at Harvard Medical School/ Boston Children’s Hospital (USA). Laboratory of Pr. Zhigang He and Dr. Judith Steen Characterization of injury response of CNS neurons at the protein level to identify new pro-regenerative and pro-survival pathways. (6 articles, 2 reviews, 3 awards)

2005-2009:  Graduate Student at the University of Lyon (France) in Molecular and Cellular Genetic Center. Laboratory of Dr. Jean-Jacques Diaz. Implication of ribosome biogenesis and translation in pathological processes. (7 articles, 2 chapters of book, 1 review, 2 awards)

•          FUNDING (selected)

2023-2026: Agence National de la Recherche (ANR-highly competitive French grant) PRC MATRIX (Principal Investigator) 530k€

2023 -2027: ANR PRC Rocketeer (co-Principal Investigator) 800k€

2022-2025: UNADEV project RING (Principal Investigator) 181k€

2021-2025: ANR PRC RIRHE (co-Principal Investigator) 340k€

2020-2021: LABEX ARCAN (co-Principal Investigator). 50k€

2019-2023: ANR JCJC. SPECCTRE (Principal Investigator). 280k€

2018-2021: Initiative Recherche Stratégique (IRS-UGA) (Principal Investigator). 90 k€

•          FELLOWSHIPS AND AWARDS

2024 award « Les Grandes Avancées Françaises en Biologie » French science academy

2016-2018 Postdoctoral fellowship re-integration from Foundation of Medical Research (France)

2016-2017 Postdoctoral fellowship from Berthe-Fouassier Foundation de France (declined)

2010-2013 Postdoctoral fellowship from William Randolph Hearst Foundation (USA). Granted 3 times

2009-2010 PhD Grant from Association against Cancer (ARC, France)

2005-2008 PhD grant from National League Against Cancer (LNCC, France)

•          INVITED PRESENTATIONS

Grenoble Institute of Neuroscience 2015 (France), Institute of Neuroscience Montpellier 2015 (France), Vision Institute Paris 2015 (France); Burke Rehabilitation and Research Center/Cornell University 2016 (USA); Centre Leon Berard Lyon 2018 (France); Molecular Chemistry department 2018 (Grenoble-Alpes University, France). French Neuroscience Meeting (Strasbourg, France) 2021; Cell Biology of Neurons and beyond , Paris (France) 2023; INMG-Melys, Lyon (France) 2023; IGBMC, 2023 Strasbourg (France), 2024 Academie des Sciences (France); 2024 EMBO Axonal Degeneration and Regeneration (Osaka, Japan)

•          INSTITUTIONAL RESPONSIBILITIES

2023- present: Deputy director at Neurodis foundation

2018- present: I am part of the scientific direction board of the Grenoble Institute of Neuroscience and I play a role in the development of the institute by organizing meetings, journal clubs and scientific animations

2019- present: Member of scientific committee at Neurodis foundation

2019- 2023 present: Member of directive committee of the animal facility PHTA Grenoble

2016- present: In charge of organizing institutional seminars at Grenoble Institute of Neuroscience

·         MEMBERSHIPS OF SCIENTIFIC SOCIETIES

2015- present: Member of the French Neuroscience Society

2015- present: Member of the American Society for Neuroscience

2021- present: Member of the French society of developmental biology

2021- present: Member of the French society of biochemistry and molecular biology

•          REVIEWING ACTIVITIES

Journal reviewer: Frontiers in Cellular Neuroscience (2018-); Molecular and Cellular Neuroscience (2019-); Neural Regeneration Research (2021-), Journal of proteomics (2022-), Breast Cancer Research (2022-); cells (2023-), Int J Mol sciences (2022-), frontiers in Neuroscience (2023-), Experimental Neurology (2022-), Cell Chemical Biology (2023-) for an average of 6 articles/year

Grant reviewer: Pasteur Institute (2017-); ANR (2024-); ERC StG (2024-)

•          EDITORIAL ACTIVITIES

2023- Guest editor of a special issue in Biology (topic Molecular Mechanisms of Axon Regeneration: Beyond Transcriptional Regulation)

2021- Guest editor of a special issue in Frontiers in Molecular Neuroscience (topic axonal growth in normal and pathological conditions)

10 selected publications:

  Customization of translational complex regulates mRNA-specific translation to control CNS regeneration. Julia Schaeffer, Noemie Vilallongue, Beatrice Blot, Nacera El Bakdouri, Charlotte Decourt, Elise Plissonnier, Blandine Excoffier, Antoine Paccard, Jean-Jacques Diaz, Sandrine Humbert, Frederic Catez, Frederic Saudou, Homaira Nawabi^*, Stephane Belin^*#  Neuron. 2023 Jul 7:S0896-6273(23)00465-8. doi: 10.1016/j.neuron.2023.06.005. PMID: 37442131^* co-corresponding ^#  and lead contact.

 The RSK2-RPS6 axis promotes axonal regeneration in the peripheral and central nervous systems Charlotte Decourt, Julia Schaeffer, Beatrice Blot, Antoine Paccard, Blandine Excoffier, Mario Pende, Homaira Nawabi, Stephane Belin. PLoS Biol. 2023 Apr 17;21(4):e3002044.  doi: 10.1371/journal.pbio.3002044. eCollection 2023 Apr.

 Guidance landscapes unveiled by quantitative proteomics to control reinnervation in adult visual system Noemie Vilallongue, Julia Schaeffer, Anne-Marie Hesse, Céline Delpech, Antoine Paccard, Yohan Couté, Stephane Belin*, Homaira Nawabi*.*co-last authors Nature Communications 2022 Oct 13;13(1):6040. doi: 10.1038/s41467-022-33799-4.PMID: 36229455 

Adult Mouse Retina Explants: From ex-vivo to in-vivo Model of Central Nervous System Injuries. Schaeffer J, Delpech C, Albert F, Belin S*, Nawabi H*. Front Mol Neurosci. 2020 Nov 25;13:599948. doi: 10.3389/fnmol.2020.599948. eCollection 2020.PMID: 33324161  * co-corresponding and co-last authors

 non-canonical inhibitory circuit dampens behavioral sensitivity to light. Takuma Sonoda, Jennifer Y. Li1, Nikolas W. Hayes, Jonathan C. Chan, Yudai Okabe, Stephane Belin, Homaira Nawabi, Tiffany M. Schmidt. Science 2020 may 1 68(6490):527-531

Doublecortin-Like Kinases Promote Neuronal Survival and Induce Growth Cone Reformation via Distinct Mechanisms. Nawabi* H, Belin* S, Cartoni* R, Williams PR, Wang C, Latremolière A, Wang X, Zhu J, Taub DG, Fu X, Yu B, Gu X, Woolf CJ, Liu JS, Gabel CV, Steen JA, He Z. *equal contribution Neuron. 2015 Nov 18;88(4):704-19. doi: 10.1016/j.neuron.2015.10.005. Epub 2015 Oct 29.

Injury-induced decline of intrinsic regenerative ability revealed by quantitative proteomics. Belin* S, Nawabi* H, Wang C, Tang S, Latremoliere A, Warren P, Schorle H, Uncu C, Woolf CJ, He Z, Steen JA. *equal contribution Neuron. 2015 May 20;86(4):1000-14. doi: 10.1016/j.neuron.2015.03.060. Epub 2015 Apr 30. (Article cited as Editor’s choice in Science Signaling 26 May 2015 Vol.8 issue378

 Short hairpin RNA against PTEN enhances regenerative growth of corticospinal tract axons after spinal cord injury. Zukor K, Belin S, Wang C, Keelan N, Wang X, He Z. J Neurosci. 2013 Sep 25;33(39):15350-61. doi: 10.1523/JNEUROSCI.2510-13.2013.

  Evidence for rRNA 2'-O-methylation plasticity: Control of intrinsic translational capabilities of human ribosomes. Erales J, Marchand V, Panthu B, Gillot S, Belin S, Ghayad SE, Garcia M, Laforêts F, Marcel V, Baudin-Baillieu A, Bertin P, Couté Y, Adrait A, Meyer M, Therizols G, Yusupov M, Namy O, Ohlmann T, Motorin Y, Catez F, Diaz JJ.Proc Natl Acad Sci U S A. 2017 Dec 5;114(49):12934-12939. doi: 10.1073/pnas.1707674114. Epub 2017 Nov 20.PMID: 29158377

p53 acts as a safeguard of translational control by regulating fibrillarin and rRNA methylation in cancer. Marce*l V, Ghayad* SE, Belin* S, Therizols G, Morel AP, Solano-Gonzàlez E, Vendrell JA, Hacot S,Mertani HC, Albaret MA, Bourdon JC, Jordan L, Thompson A, Tafer Y, Cong R, Bouvet P, Saurin JC,Catez F, Prats AC, Puisieux A, Diaz JJ. *equal contribution Cancer Cell. 2013 Sep 9;24(3):318-30. doi:10.1016/j.ccr.2013.08.013.

Over the last 6 years, I set-up my independent lab on the molecular mechanisms of axon regeneration in the central nervous system. Since then, I published 10 scientific articles/reviews in peer reviewed journal. Several publications have been accepted in the most prominent journal in the field of neuroscience (Neuron) and general audience journals (Nature Communication, PLoS Biology, Science). Those listed below demonstrated my impact in the field of axon regeneration and protein translation. Since my establishment as independent researcher, I demonstrated my ability to secure grants (competitive national Grant form ANR, UNADEV…) and successfully drive project leading to major breakthroughs and publications. I have also set-up key and fruitful collaboration to develop project around mass spectrometry, RNAseq analysis, neuronal recording/stimulation and ribosome structure as represented by the number of common publications with collaborators.

During my PhD with Dr Jean-Jacques Diaz, I identified modifications of the ribosome induced by different physio-pathological stresses such as virus infection (Belin et al., RNA, 2010), cancer progression (Belin* et al., Plos One, 2009a and b) and cancer development (Marcel* et al., Cancer Cell, 2013).  My work has profound implication in the reinterpretation of the role of the ribosome and the translational complex in the regulation of translation. Indeed, my work has shed light on the existence of different pools of ribosomes and the direct involvement of ribosome composition in translation regulation of specific mRNA. This led to the emergence of several studies on rRNA chemical modifications role on translation.  I then pursued my career as a postdoc in the laboratories of Pr Zhigang He and Dr Judith Steen (Harvard Children Hospital). I extended my analysis of translation control during stress by investigating the injury response of central nervous system (CNS) neurons to injury. I developed a quantitative based proteomics approach of pure neuron population. Based on this analysis, I demonstrated that c-myc is essential for neuronal survival and can induce strong CNS axon regeneration when expressed before or after injury. In addition this protein synergizes with mTOR and JAK/STAT pathways to induce strong regeneration close to the original targets (Belin* et al., Neuron, 2015). Second, I demonstrated that DCLK2 is essential for neuron survival by controlling axonal transport and for axonal regeneration by promoting growth cone formation after injury by the stabilization of microtubules and actin (Nawabi* et al., Neuron, 2015a). Finally I highlighted the crucial role of translation regulation during injury (Belin* et al., Neuron, 2015b). I established an independent laboratory in the Grenoble Institute of Neuroscience (France) in 2018 in order to analyze the exact composition of the translational complex (ribosome, translation and associated factors) and define its implication into the control of protein synthesis and its role for neuroprotection and regeneration in adult nervous system. I have developed a new ex-vivo model of axon regeneration and injury that reproduces all the features of the in-vivo model. This powerful system is perfect to analyze molecular events at a single axon resolution and is particularly pertinent for local translation analysis (Schaeffer et al, Frontiers in Mol Neuro, 2021). I participated to the characterization of axon guidance modalities in adult during regeneration. Using proteomic analysis, we defined a comprehensive map of guidance cue in the visual system (Vilallongue et al., Nat Communication 2022). I also determined that ribosomal proteins composition can differ according mice organs (Brunchauld et al in preparation). My analysis of the translational complex also reveals HTT as a new ribosome interactant, controlling specifically mRNA translation important for CNS axon regeneration (Schaeffer et al, Neuron 2023). Finally, I characterized the central role of RSK pathway and the phosphorylation of ribosomal protein in both peripheral (PNS) and central (CNS) nervous system regeneration (Decourt et al, PLoS Biology 2023). My work has shed light on key molecular mechanisms necessary to promote axon regeneration and circuit formation in adults and reinforces the notion of specialized ribosome.