The Institute of NeuroPhysiopathology (INP) is a training and research centre of excellence that combines basic and translational research to study neural cell organisation, function and interaction, the molecular and cellular bases of major brain diseases, and to develop innovative cellular and molecular therapeutic strategies.
The PFNT Facility is a coherent set of exploration tools in neurobiology allowing research at the molecular, cellular and integrated levels.
Dans son édition du vendredi 31 mai 2024, La Provence mettait l'INP à l'honneur dans son dossier sur la maladie d'Alzheimer. Le Pr Mathieu Ceccaldi (Service de Neurologie et Neuropsychologie Adultes & équipe 9) était interrogé sur les nouveaux traitements, pendant que François Devred (équipe 9) et Santiago Rivera (équipe 1) étaient eux interrogés sur les travaux des "six équipes qui bossent à temps plein dans ce "gros" laboratoire français de recherche sur Alzheimer"
Carla Djian joined our team for her 1-month M1 internship. Carla is a neuroscience master student at AMU.
Welcome!
The last 2 weeks, several INP teams hosted M1 students for their APP (Apprentissage Par Projet). For many, it was a first experience in a research lab! Each APP is organized around a larger project (Alzheimer's Disease, Myelin, Functional imaging) and students rotate between different labs of NeuroMarseille.
Thanks to Laurence, Christine (Team 1), Theresa, Fanny (Team 7), Naz and Marine (Team 4) for mentoring all these students!
Du lundi 15 au vendredi 19 avril 2024 s'est tenue, toujours avec succès, la troisième édition de la formation MedIM (Méthodes d'étude des Interactions Moléculaires) co-organisée par la Plateforme INteractome Timone (PINT) de l’INP, la plateforme de Biologie Structurale de l’AFMB et les plateformes de l’IMM, toutes trois labellisées "Plateformes Technologiques Aix-Marseille".
Louise (our sustainable development referent) led a Ma Terre en 180 Minutes workshop at the annual seminar for laboratory directors (DU) at DR12 of the CNRS in Saint-Raphaël, on April 18.
40 laboratory directors from the Provence and Corsica regions were able to experience the workshop developed by colleagues from the Observatoire des Sciences de l'Univers de Grenoble (OSUG). These directors had to collectively identify the levers of action for a research team in order to reduce their annual greenhouse gas emissions by 50% in a very short space of time.
On 4 April, Nora Essakhi, Roberta Stacchini and Alexandre Bertucci, PhD students in the GlioME team, presented their poster at the 5th Scientific Annual Conference - Institut Cancer et Immunologie (ICI) on the theme of "CAR T cells, advances in cellular engineering and future challenges in cancer therapy".
Nora's work on "GD3, a promising therapeutic target for CAR-T cells against glioblastoma stem cells", was recognised by the scientific committee, which awarded her the prize for best poster. Well done Nora!
The review "GD3 ganglioside is a promising therapeutic target for glioma patients" is now published in Neuro-oncology Advances.
Congratulations to Victoria Hein, Nathalie Baeza-Kallee, Alexandre Bertucci, Carole Colin, Aurélie Tchoghandjian, Dominique Figarella-Branger, Emeline Tabouret for this work.
Salma Laftimi, a L3 student at AMU, joined Team 4 for her internship. She will stay with us for 1 month.
Welcome!
The NeuroCyto lab is looking to hire a postdoctoral fellow for an exciting project at the interface of microscopy and neuronal cell biology.
Deadline for application: January 15th, 2023. Starting date (flexible): April 2023.
About the position and project
Dans son édition du vendredi 31 mai 2024, La Provence mettait l'INP à l'honneur dans son dossier sur la maladie d'Alzheimer. Le Pr Mathieu Ceccaldi (Service de Neurologie et Neuropsychologie Adultes & équipe 9) était interrogé sur les nouveaux traitements, pendant que François Devred (équipe 9) et Santiago Rivera (équipe 1) étaient eux interrogés sur les travaux des "six équipes qui bossent à temps plein dans ce "gros" laboratoire français de recherche sur Alzheimer"
Carla Djian joined our team for her 1-month M1 internship. Carla is a neuroscience master student at AMU.
Welcome!
The last 2 weeks, several INP teams hosted M1 students for their APP (Apprentissage Par Projet). For many, it was a first experience in a research lab! Each APP is organized around a larger project (Alzheimer's Disease, Myelin, Functional imaging) and students rotate between different labs of NeuroMarseille.
Thanks to Laurence, Christine (Team 1), Theresa, Fanny (Team 7), Naz and Marine (Team 4) for mentoring all these students!
Du lundi 15 au vendredi 19 avril 2024 s'est tenue, toujours avec succès, la troisième édition de la formation MedIM (Méthodes d'étude des Interactions Moléculaires) co-organisée par la Plateforme INteractome Timone (PINT) de l’INP, la plateforme de Biologie Structurale de l’AFMB et les plateformes de l’IMM, toutes trois labellisées "Plateformes Technologiques Aix-Marseille".
Louise (our sustainable development referent) led a Ma Terre en 180 Minutes workshop at the annual seminar for laboratory directors (DU) at DR12 of the CNRS in Saint-Raphaël, on April 18.
40 laboratory directors from the Provence and Corsica regions were able to experience the workshop developed by colleagues from the Observatoire des Sciences de l'Univers de Grenoble (OSUG). These directors had to collectively identify the levers of action for a research team in order to reduce their annual greenhouse gas emissions by 50% in a very short space of time.
On 4 April, Nora Essakhi, Roberta Stacchini and Alexandre Bertucci, PhD students in the GlioME team, presented their poster at the 5th Scientific Annual Conference - Institut Cancer et Immunologie (ICI) on the theme of "CAR T cells, advances in cellular engineering and future challenges in cancer therapy".
The review "GD3 ganglioside is a promising therapeutic target for glioma patients" is now published in Neuro-oncology Advances.
Congratulations to Victoria Hein, Nathalie Baeza-Kallee, Alexandre Bertucci, Carole Colin, Aurélie Tchoghandjian, Dominique Figarella-Branger, Emeline Tabouret for this work.
Salma Laftimi, a L3 student at AMU, joined Team 4 for her internship. She will stay with us for 1 month.
Welcome!
Chiara Bastiancich
"Characterization of the glioblastoma post-surgical microenvironment for developing treatment strategies to prevent tumor recurrence"
Glioblastoma (GBM) is the most frequent and aggressive primary brain tumour in adults. The standard of care therapy includes surgery followed, several weeks later, by radiotherapy and chemotherapy but inevitably leads to lethal recurrences. The local delivery of active agents is an attractive approach for GBM as it expands the number of drugs that can be used to treat this devastating disease bypassing the blood-brain barrier (BBB). Our prior work with a nanomedicine hydrogel (GemC12-LNC) demonstrated delayed recurrence onset when administered post-surgery. To enhance its anticancer efficacy, we hypothesized combining it with an immunomodulatory drug. However, the impact of surgery on tumor recurrence lacks characterization, hindering combinatory therapy development.
In this study, we investigated the impact of surgery on the brain and the post-surgical microenvironment (SMe) using a syngeneic mouse tumor resection model. We explored BBB opening via PET-SPECT and immune cell dynamics using two-photon imaging, whole mount staining, immunohistochemistry, and flow cytometry. We determined the time frames for recurrence development and observed a temporary BBB disruption that recovered within a week, providing a therapeutic window for systemic drug administration. Immune cell differences between unresected and recurrent tumors in mice revealed overexpression of pro-tumoral macrophages, border-associated macrophages, and reactive microglia in resected tumors. Combining local GemC12-LNC with systemic SMAC-mimetic drug reversed this immune response, delaying recurrence onset and increasing survival in GBM-bearing mice.
This study provides critical SMe time frames and immune cellular targets, enabling rational combinatory treatment design to delay GBM recurrence onset. These findings hold promise for translating into novel therapies aimed at improving GBM patient outcomes.
Pavlo présentera ses projets en cours sur le développement de nanoparticules lipidiques (LNPs) pour le transport d’ARNm dans les tissus et en particulier au travers de la BHE, dans le cerveau.
Nicolas SERGEANT is an Inserm Research Director who, from the natural history of Alzheimer’s disease (AD), the development of cell drug-screening models against AD and Tauopathies, and also thanks to a long-term collaboration with the organic chemistry laboratory of Pr. Patricia Melnyk has co-developed small anti-Alzheimer’s drugs that mitigate the pathophysiology of Alzheimer’s disease. One of these is currently in clinical phase II by a PharmD Company. He is also delighted to identify and validate biomarkers to assess neurodegenerative processes in neurological disorders and develop gene therapy using a molecular decoy strategy.
Seminar title: Bio-orthogonal chemistry as a tool for biological target identification and deciphering the mechanism of action of small anti-Alzheimer drug candidates
Abstract:
Our research has the potential to significantly impact the development of Alzheimer’s disease (AD) modifying drugs. Targeting amyloid deposition and neurofibrillary degeneration, along with neuroinflammation, is a challenging pharmacological strategy. We have synthesized five families of drugs, originally derived from chloroquine or amodiaquine and computer-assisted pharmacophore design, to achieve this goal (Sergeant et al., 2019; Tautou et al., 2021). Among these, novel polyaminobiaryl compounds, including PEL24-199, were produced and shown to repress amyloid production in vitro. In vivo, this water-soluble drug led to the recovery of short and long-term memory in transgenic animal models of both pathological processes of AD. This recovery was associated with a reduced Tau and amyloid pathology and the reduction of astrogliosis and neuroinflammation in both models. The drugs’ target is unknown, and based on the pharmacophore chemical structure, bioorthogonal chemistry was used to covalently couple the drug to the biological target and click-chemistry to isolate, purify, and identify the target of our drugs. This strategy thus enables, based on a phenotyping hit-screening, the identification of potent novel drug-directed development of anti-Alzheimer disease strategies, offering hope for the future of AD treatment.
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