19/01 : LE 13H DE AUDREY FERRAND @ RESTORE

Deciphering the intestinal epithelium regulation : a multidisciplinary approach

I obtained in 2004 a PhD in Pharmacology from the University of Toulouse. My research interest in the laboratory of Digestive Biology (INSERM U531) was to decipher the signaling pathways involved in the initiation of colon and pancreas cancers.

In 2005, I joined the laboratory of Jeffrey Settleman at the Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School, in Boston (USA) where I characterized the differential drug response of mutated EGFR in non-small cell lung cancer. In 2006, I moved to the Surgery Department of the University of Melbourne (Australia) where I identified the crucial role of gastrin precursors in the tumor-initiating capacity of CD133-positive colon cancer cells.  In 2009, I have been recruited as a junior assistant professor (INSERM CRCN) to establish a research program aiming to identify therapeutic targets in colorectal cancer.

Since 2018, I lead a research group at the IRSD (Institut de Recherche en Santé Digestive) studying the interactions between the intestinal epithelium and the environment, either luminal or stromal. By combining morphological, functional, pharmacological and microfluidic approaches to 3D cell primocultures of colorectal organoids and fibroblasts, we study the interactions between the intestinal epithelium and the fibroblasts in the context of inflammatory bowel diseases and the risk of tumorigenesis.

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CR1 INSERM, Institut de Recherche en Santé Digestive,

INSERM u1220, INRA u1416, Université Paul Sabatier, Ecole Nationale Vétérinaire de Toulouse, Toulouse.

12/01 : LE 13H DE CHRISTOPHE PELLEFIGUES @ RESTORE

Contrôle de la résolution de l'inflammation par les basophiles dans un modèle de lésion cutanée chez la souris âgée

Pro-resolution M2-like macrophages are critical for wound healing. Aging-associated systemic chronic inflammation alters their functions and favors the development of chronic wounds, a major morbidity in elderly patients. Basophils, rare circulating granulocytes known for their pro-inflammatory roles in allergic and parasitic diseases, can potently promote M2-like macrophage’s pro-resolution functions due to their high innate production of type 2 cytokines.

In this work in progress, we explore the roles of basophils in skin wound healing using mice models of specific basophil depletion or gene deletion, and reanalysis of published transcriptomic datasets. We show that basophils infiltrate skin wounds early during inflammation and express Interleukin 4 (IL-4) for at least three weeks. They inhibit the accumulation of pro-inflammatory monocytes/macrophages during the resolution phase in an IL-4 dependent manner and accelerate wound closure while favoring keratinocyte differentiation during re-epithelialization.In aged mice, basophils have a more activated and immature phenotype but unexpectedly show enhanced pro-resolution properties.

Thus, basophils display pro-resolution properties favoring the skin wound healing response in both adult and elder mice. Unraveling the molecular mechanisms controlling these properties may hold promise to restore optimal healing and resolution in the elderly.

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CR CNRS au Centre de Recherche sur l’Inflammation à Paris, dans l’équipe de Nicolas Charles et Ulrich Blank “Basophiles, mastocytes et Immunopathologie”

17/11 : LE 13H DE ALAIN DOGLIO @ RESTORE

Etiopathology of gingival inflammation: towards a new paradigm based on virus - bacteria synergy

Periodontitis is one of the most common human inflammatory condition. This disease is responsible for tooth mobility and tooth loss, and it is also a significant risk factor for dozens of seemingly unrelated systemic illnesses. A polymicrobial dysbiosis model was proposed for periodontitis with colonization of subgingival teeth sites with different Gram-negative bacteria, identified as “keystone pathogens”.

So far, most studies have focused on bacterial populations, while less attention has been paid to the viral component. We notably investigated the pathogenic role of the Epstein-Barr virus in periodontitis showing that the virus can promote breakdown of innate barriers, pro-inflammatory signaling, and immune dysregulation and thus deeply worsening severity of the disease

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Alain DOGLIO is the director of the MICORALIS laboratory (Université Côte d’Azur, Nice), a research team focused on oral microbiology, immunity and global health. He is also the head of the cell therapy facility of the CHU de Nice.

20/10 : LE 13H DE ARGYRIS PAPANTONIS @ RESTORE

Lessons for disease learned from cellular ageing: a 3D genome perspective

We wish to uncover the rules governing gene expression in response to developmental and extra-cellular cues. Genome architecture is thought to be a major determinant in this. What we strive to understand is how chromatin (re)folds to accommodate responses to such cues in 3D nuclear space and dynamically over time. In the end, we anticipate these rules to be general ones, which once deciphered will allow us to predict how a cell might respond upon signalling, in the context of disease, or during cellular ageing.

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Argyris Papantonis studied biology at the University of Athens, Greece, where he also obtained his PhD in gene expression regulation. He did his postdoctoral work with Peter Cook at the University of Oxford, where he also served as a Lecturer for Biochemistry. In 2013, he was appointed as a Junior Group Leader at the University of Cologne, and in 2018 he was elected Professor of Translational Epigenetics at the University of Goettingen. Currently, he is also the Speaker of the SPP2202 German Priority Program for “3D genome organization in development and disease”.

13/10 : LE 13H DE EMILIE GREGORI @ RESTORE

Bénéfices & Applications de la technologie CyTOF pour la cytométrie et l’imagerie tissulaire

Avoir la possibilité de monter en puissance dans le nombre de paramètres à étudier simultanément en cytométrie et en imagerie tissulaire est un enjeu crucial pour vos recherches.
L’objection majeure à cette escalade est toutes les limites des technologies liées aux fluorochromes : compensation, déconvolution, autofluorescence, normalisation, etc… Imaginez que toutes ces contraintes soient enlevées.
Entrevoir des panels de 50 paramètres ou plus en cytométrie et 35 paramètres en imagerie tissulaire devient beaucoup plus facile. C’est la solution que Standard Biotools vous propose. Recentrez-vous sur vos questions biologiques nous nous occupons du reste.

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Field Application Specialist
Standard Biotools

22/09 : LE 13H DE PAULINE ASSEMAT @ RESTORE

Mécano-biologie des tissus hétérogènes par changement d’échelles :application à l’ostéosarcome

Collaborations: A. Gomez-Brouchet (PUPH, CRCT), J Sales de Gauzy (PUPH, IMFT), A. Mancini (Ph.D st), A Moreno (Ph.D), M Quintard (DR CNRS, IMFT), P Swider (PR Université de Toulouse, IMFT)

Résumé:
L’ostéosarcome est une tumeur osseuse primitive qui survient principalement chez les adolescents et les jeunes adultes. Le taux de survie à 5 ans est de 70% et chute à 25% pour les patients présentant des métastases ou ne répondant pas au traitement. De nouveaux développements sont nécessaires pour améliorer la prise en charge spécifique des patients. Ce type de tumeurs présente de fortes hétérogénéités spatiales dans la micro-architecture osseuse, la densité cellulaire mais aussi dans la réponse aux traitements. A l’échelle tissulaire et du point de vue de la biophysique, le micro-environnement de l’ostéosarcome peut être considéré comme un milieu poreux fortement hétérogène sensible aux effets mécaniques.

Nous proposons une méthode de changement d’échelles pour caractériser les propriétés mécaniques de ce milieu. La méthodologie est adaptée à des images de grandes tailles et notamment les images binaires de coupes histologiques d’ostéosarcome obtenues en routine clinique. Le transport et l’élasticité sont étudiés. Les paramètres équivalents de type perméabilité tissulaires et coefficients de raideurs tissulaires sont déterminés avec fiabilité.

Dans une étude rétrospective préliminaire, des corrélations entre les propriétés mécaniques tissulaires et les paramètres cellulaires sont démontrées. Une cohorte réduite de patients montre que la réponse au traitement peut être corrélée à l’architecture du micro-environnement et à ses propriétés mécaniques. Ces quantifications pourraient ainsi ouvrir la voie à la définition de nouveaux marqueurs mécano-biologiques de l’ostéosarcome et de sa dynamique complexe dans l’espace et le temps.

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CR CNRS Institut de Mécanique des Fluides de Toulouse | IMFT · Milieux Poreux et Biologiques
 

13/07 : LE 13H DE PETER J. H. SCOTT @ RESTORE

PET Imaging and Theranostics in the Age of Personalized Medicine

With the emergence of theranostics and the expected impact of artificial intelligence on our work, it is an exciting time to be in the field of nuclear medicine. For about 60 years, the Division of Nuclear Medicine at the University of Michigan has been developing radiopharmaceuticals for diagnostic imaging (e.g. positron emission tomography, PET), as well as radiotherapy, and translating them for clinical care.

This presentation will give an overview of our work providing clinical care to the University Hospital, as well as both the clinical and basic research being conducted by our division today, including new methods for producing PET imaging agents, and the new radiopharmaceuticals being developed and translated at our academic medical center. The presentation will conclude imaging the future impact of Artificial Intelligence from bench-to-bedside.

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Pr. Peter J. H. Scott FRSC CChem (born 27 July 1979) is a British and American chemist and radiochemist who is an Associate Professor of Radiology and Pharmacology, as well as a Faculty Scientist in the Interdepartmental Program in Medicinal Chemistry and a Core Member of the Rogel Cancer Center at the University of Michigan in the United States

23/06 : LE 13H DE CARINE JOFFRE @ RESTORE

Autophagy, a major metabolic regulator involved in AML therapy resistance

Malgré l’efficacité des chimiothérapies et l’arrivée de thérapies ciblées, les rechutes restent fréquentes et le pronostic vital des patients atteints de Leucémies Aiguës Myéloïdes (LAM) faible. Il est maintenant admis que la résistance aux traitements des cellules LAM nécessite une adaptation de leur métabolisme. Nous émettons l’hypothèse que cette adaptation soit contrôlée par l’autophagie, un processus catabolique impliqué dans la régulation du métabolisme cellulaire ayant des effets ambivalents sur la biologie des cellules cancéreuses.

Comprendre son mode de régulation et les mécanismes via lesquels elle soutient la croissance des cellules leucémiques va donc aboutir à l’identification de nouvelles cibles dont la modulation, en association aux traitements conventionnels, devrait perturber le métabolisme des LAM et ainsi rétablir leur sensibilité aux traitements.

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Dr Carine JOFFRE

Chercheuse au CRCT, Équipe METAML.

16/06 : LE 13H DE MAUDE LE GALL @ RESTORE

Gastric and intestinal adaptations in response to bariatric surgery and their contribution to glycemic improvement

The team gathers physiologists of the gastro-intestinal tract, basic scientists and clinicians (digestive surgeons, gastroenterologists and nutritionists) to develop basic and transitional researches to study gastrointestinal adaptations in response to obesity, surgical remodeling, and nutritional status (undernutrition / malnutrition). More specifically they deciphered mechanisms of gastrointestinal adaptations in response to weight-loss surgical therapies (bariatric surgeries) and massive intestinal resection, main cause of intestinal failure (short bowel syndrome).

The pharmacotherapy of obesity remains inconstant and today bariatric surgeries are the only effective treatments when obesity becomes morbid. While these surgeries are generally extremely beneficial especially on comorbidities as Type 2 Diabetes Mellitus, non-alcoholic fatty liver disease … they can also lead to severe malnutrition and fragility.

Combining experimental research in preclinical rat models with clinical studies, we identified differences in intestinal adaptation that contribute to improve glucose homeostasis after the 2 most popular bariatric surgeries: Roux-en-Y Gastric Bypass (RYGB) and Vertical Sleeve Gastrectomy (VSG).

We demonstrated how gastric and intestinal adaptations contribute to increase the secretion of Glucagon Like Peptide 1, GLP-1 an hormone that potentiates insulin secretion in response to hyperglycemia. In addition, we identified the stomach as a putative source of GLP-1. Finally, we revealed that RYGB increases intestinal glucose disposal whereas VSG delays glucose absorption; thwarting the intuitive idea that RYGB and VSG must share a common mechanism of action for similar efficiency on glycemic improvements.

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Dr Maude LE GALL

Directrice de recherche au centre de recherche sur l’inflammation à Paris (UMR 1149 INSERM-Université Paris Diderot).

Co-directrice de l’équipe ” Plasticité des muqueuses gastro-intestinales dans les pathologies nutritionnelles et après chirurgie (PIMS)”

09/06 : LE 13H DE JULIE BATUT @ RESTORE

From olfactory organ formation using embryonic, mathematical and microfluidic models to a PhD student mentoring programme with CBI and Femmes & Sciences responses?

Julie Batut est biologiste, spécialiste de la neurogenèse ainsi que de l’identité et la forme des cellules au cours du développement embryonnaire. Chercheuse au CNRS, elle étudie la mise en place de l’épithélium olfactif chez l’embryon de poisson zèbre en utilisant de l’imagerie en temps réel et un modèle mathématique. Elle est également engagée au sein de l’association Femmes & Sciences où elle développe en autre le mentoring pour les doctorantes et récemment au sein des Chemins Buissonniers pour transmettre ses passions, la recherche et l’embryologie, au plus grand nombre.

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Dr Julie BATUT

Chargée de recherche CNRS

Centre de Biologie Intégrative (CBI) – TOULOUSE