Centre de Référence Maladies Rares

U1035 INSERM

Biotherapy of genetic diseases, inflammatory disorders and cancer (BMGIC)

FR: Biologie Fondamentale Appliquée à la Médecine

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Next meetings

team meetings, conferences, thesis

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Journal club

The 29 January 2018 from 14:30 to 15:30.

réunion labo : équipe MiRCaDe

The 22 January 2018 from 14:30 to 15:30.

réunion labo : équipe hémato

The 15 January 2018 from 14:30 to 15:30.

réunion labo : équipe immuno-dermato

The 08 January 2018 from 14:30 to 15:30.

Réunion labo : équipe dermato

The 18 December 2017 from 14:30 to 15:30.

réunion labo : équipe biothérapie

The 11 December 2017 from 14:30 to 15:30.

Journal club

The 04 December 2017 from 14:30 to 15:30.

journée Fr TransBioMed

The 30 November 2017 at 09:00.

Merci de noter la date de La Journée Scientifique de la Fédération de Recherche TransBioMed qui aura lieu le jeudi 30 novembre 2017 au Domaine du Haut-Carré à Talence.

Si vous avez d'éventuelles questions, n'hésitez pas à contacter directement les organisateurs de la session 2017 :
Marion Bouchecareilh - BaRITOn Inserm U 1053 - marion.bouchecareilh@ibgc.cnrs.fr
Isabelle Coupry - MRGM Inserm U1211 - isabelle.coupry.ext@chu-bordeaux.fr

Nous vous enverrons très prochainement le programme détaillé de la journée, mais vous êtes invités à vous inscrire dès maintenant sur le site internet et à proposer votre participation aux sessions posters et flash-posters :

http://www.transbiomed.u-bordeaux.fr/journee-scientifique-fr-transbiomed-2017/

Read more

réunion labo : équipe MiRCaDe

The 27 November 2017 from 14:30 to 15:30.

réunion labo : équipe hémato

The 20 November 2017 from 14:30 to 15:30.

réunion labo : équipe immuno-dermato + focus accord confidentialité

The 13 November 2017 from 14:30 to 15:30.

en début de réunion : Karine ABADO, responsable du Service "Recherche Contractuelle et Valorisation Commerciale" Direction Innovation, Partenariats, Entreprises de l'Université de Bordeaux, viendra faire une présentation du focus accord confidentialité et répondra aux questions que vous souhaiterez poser.

Réunion labo : équipe biothérapie

The 06 November 2017 from 14:30 to 15:30.

réunion labo- équipe Dermato

The 30 October 2017 from 14:30 to 15:30.

Journal Club : Nano String Technology

The 23 October 2017 from 14:30 to 15:30.

Présentation de la Nano String Technology organisé par Katia Boniface.
Le thème de ce journal club sera la technologie Nanostring®, deux personnes de cette société viendront présenter la technologie : principe, avantages, applications...

La technologie du Nanostring® permet d'étudier notament le transcriptome des cellules même dans les situations où la quantité d'ARN est limitée (analyse simultanée de 700/800 gènes). La technologie est disponible sur notre site (acquisition de l'appareil par le CHU de Bordeaux)
Le principe repose sur 2 étapes clés: 2 sondes sont conçues spécifiquement pour chaque cible d'intérêt:

- Une sonde de capture, couplée à la biotine, utilisée pour immobiliser les molécules d'intérêt sur un support dédié au comptage.
- Une sonde appelée « rapporteur », spécifique de la molécule d'intérêt, qui contient une succession de 6 fluorochromes de 4 couleurs différentes, dont l'arrangement définit un code-barre propre à chaque cible d'intérêt. Ce code-barre permet la sensibilité de cette technique et l'analyse d'une faible quantité de matériel biologique.

Suivant ce principe, 800 transcrits peuvent être comptés simultanément.
La détection est directe (ARN, lysats cellulaires), sans étape de reverse transcription ou d'amplification par PCR.
Une technologie 3D analysant ADN, ARN et protéines à partir d'un même échantillon est également en développement.

La réunion sera suivie d'une table ronde pour permettre aux personnes qui le souhaitent de discuter plus en détails de vos projets et de l'utilisation possible de la technologie

réunion labo-équipe MirCaDe

The 16 October 2017 from 14:30 to 15:30.

thèse de Pierre-Yves Dumas. Equipe Hématologie

The 10 October 2017 at 10:00.

PIERRE-YVES DUMAS soutiendra publiquement ses travaux de thèse (Biologie Cellulaire et Physiopathologie) intitulés :

"Microenvironnement médullaire et résistance des LAM FLT3-ITD aux inhibiteurs de tyrosine kinase. Rôle pivot du récepteur TAM AXL."

dirigés par Monsieur Jean-Max PASQUET.
Lieu : Université de Bordeaux, 146 rue Léo Saignat, 33000 Bordeaux, salle des thèses

réunion labo : équipe hémato - ANNULEE

The 09 October 2017 from 14:30 to 15:30.

réunion labo : équipe dermato

The 02 October 2017 from 14:30 to 15:30.

réunion labo : équipe biothérapie

The 25 September 2017 from 14:30 to 15:30.

réunion labo : équipe Immuno-dermato

The 18 September 2017 from 14:30 to 15:30.

réunion labo de rentrée. Hygiène et sécurité

The 11 September 2017 at 14:30.

informations de rentrée
Le point sur l'hygiène et la sécurité

conférence Jean Krutmann

The 04 July 2017 at 14:00.

Invitation : Alain Taïeb – Inserm U 1035

Jean Krutmann
IUF – Leibniz Research Institute for Environmental Medicine
IUF – Leibniz-Institut für umweltmedizinische Forschung gGmbH
Düsseldorf

“The AHR as a sensor of environmental stress to skin.”

Mardi 4 juillet à 14h00
Salle de conférences de la Plateforme Génomique fonctionnelle – site de Carreire zone sud, université de Bordeaux

Chronic exposure to solar radiation is a major cause of environmentally-induced skin aging, which is therefore traditionally referred to as photoaging. We and others have shown that within the solar spectrum, wavelengths in the Ultraviolet (UV) B and A range, but also visible light and near infrared radiation can cause skin aging (reviewed in 1). More recent studies suggest, however, that extrinsic skin aging is more than photoaging and, in particular, that traffic related air pollution independently contributes to skin aging. In epidemiological studies chronic exposure to ambient particulate matter (PM) as well as nitrogen oxide (NO2) was found to be significantly associated with more pigment spots on cheeks of elderly Caucasian as well as Han Chinese (2,3). This association was modified by genetic variants. Accordingly, we observed a significant interaction between air pollution and Arylhydrocarbon Receptor (AHR) /Arylhyrocarbon Receptor Repressor genetic risk scores on cheek lentigines. Women with a high genetic risk score for AHR/AHRR develop 52 % more lentigines on the cheeks after an increase of 4.45 μg/m3 (IQR) in PM2.5 and 36 % more lentigines after an increase of 5.54 μg/m3 (IQR) in PM10, whereas there was no association in women with a low risk score. We thus show that gene environment interactions are involved in environmentally-induced skin aging in general and air pollution-induced lentigines formation in particular. These results also indicate that AHR signaling is involved in environmentally-induced skin aging. In line with this assumption are in vitro studies in which topical application of ambient relevant Diesel Exhaust Particles caused AHR-dependent gene transcription in ex vivo human skin models. Interestingly, AHR signaling may also be induced in skin by UVB irradiation (4) and critically contribute to photocarcinogenesis. In contrast to AHR +/+ mice, AHR -/- animals developed 50 % less skin tumors in a chronic UVB irradiation study. In subsequent experiments we found that this procarcinogenic action of AHR signaling is due to a negative regulation of DNA damage responses in UVB irradiated keratinocytes which critically involves the interaction of AHR with p27 (5). Taken together these studies suggest that AHR might be a molecular target for the prevention of extrinsic skin aging / skin cancer (6). We have therefore recently developed a competitive AHR antagonist which can be topically applied to human skin and inhibit UVB radiation as well as air pollution-induced AHR activation in human skin cells in vitro and in vivo (7).

Conférence Beat Imhof

The 14 March 2017 at 11:00.

Salle de Conférences de l’IBGC

Beat Imhof
Department of Pathology and Immunology, University of Geneva

Invitation : Alain Taieb – Inserm U 1035

» New Molecular Targets for Angiogenesis driven diseases. »

Angiogenesis is a process that plays a key role in tumor development, wound healing and chronic inflammation. We and others found that recruitment of a subpopulation of human angiogenic monocytes and the production of the matricellular molecule Olfml-3 are two critical cues. We studied extravasation of these monocytes by using human tumor xenograft models and live-imaging of trans endothelial migration of proangiogenic monocytes composed of CD14dimCD16+ patrolling and CD14+CD16+ intermediate cells. We found that the inflammatory cytokine IFNg-increased expression of CX3CL1 chemokine on vascular endothelium and mediates retention of pro-angiogenic monocytes in the vascular lumen. Expression of the angiogenic factor VEGF and the inflammatory cytokine TNFa by tumor or inflamed cells specified a molecular expression program in the endothelium that caused CX3CL1 repression and allowed extravasation of these monocytes. The de novo recruited proangiogenic monocytes boosted tumor angiogenesis by secreting MMP-9, leading to release of matrix bound VEGF, and by this way amplifying the entry of more proangiogenic monocytes into tumors. Uncovering the luminal retention role of CX3CL1 and this cancer-related recruitment process sets the stage for future approaches in tumor and chronic inflammation therapies. The second mechanism that will be described is driven by matricellular molecules that bridge the cell surface to the extracellular matrix and forms a microenvironment for angiogenic endothelium. Our laboratory recently described Olfactomedin-like 3 (Olfml3), a novel matricellular molecule with the ability to regulate vascular remodeling under normal and pathological conditions. Olfml3 is expressed at high levels during development in the presumptive vasculogenic regions of the embryo. Yet, Olfml3 knockout mice are viable but exhibit mild vascular morphogenetic defects. Expression of Olfml3 in adult animals is largely limited to tissue undergoing remodeling including placenta and tumors. Tumor-derived Olfml3 is produced by both tumor endothelial cells and accompanying pericytes, and deposited in the perivascular compartment. Olfml3 alone or through binding to bone morphogenetic protein 4 (BMP4), a potent pro-angiogenic growth factor, enhances the canonical SMAD1/5/8 signaling pathway required for BMP4-induced angiogenesis. Blockade of Olfml3 by anti-Olfml3 antibodies is highly effective in reducing tumor vascularization, pericyte coverage, and tumor growth. These findings indicate that Olfml3 blockade provides a novel strategy to control tumor growth by targeting two distinct cell types within the tumor microenvironment using a single matricellular molecule. Given the potential side effects and resistance linked to current anti-angiogenic therapies, a better understanding of novel angiogenic signaling circuits can accelerate the development of alternative and more selective strategies. Blocking Olfml3 and pro-angiogenic monocytes are two examples.

conférence Radiothérapie interne du mélanome métastasé

The 09 February 2017 at 11:00.

Salle de Conférences de l’IBGC

Françoise Degoul – Jacques Rouanet – Hussein Akil
Université d’Auvergne – UMR 990

Invitation : Muriel Cario-André – Inserm U1035

« Radiothérapie interne du mélanome métastasé »

L’UMR 1240 INSERM/Université Clermont Auvergne propose une approche focalisée principalement, mais de façon non exclusive, vers le diagnostic et le traitement de la maladie cancéreuse. Notre stratégie repose sur le développement de vecteurs moléculaires capables de cibler un tissu ou un mécanisme biochimique particulier. Le radiomarquage de ces vecteurs ouvre des champs d’application prometteurs pour la radiothérapie interne (RTI) et/ou l’imagerie scintigraphique de nombreuses pathologies parmi lesquelles le mélanome. Les molécules traceurs de mélanines sélectionnées pour l´imagerie et la thérapie sont très sélectives des tissus pigmentés (Cachin et al, 2014 ; Viallard et al, 2014 ; Rbah-Vidal et al, 2016). Cette propriété implique une sélection des patients à inclure lors du transfert clinique, la phase I consistera d´ailleurs en une étude d´escalade de dose d´[131I]ICF01012. Nous avons montré que des petites molécules d´ADN (CoDbait) désorganisant les systèmes de réparation potentialisent l´effet de la RTI (Viallard et al, 2016). Des études sur des sphéroïdes pour analyser la réponse à la RTI en fonction de la pigmentation et du statut BRAF/PTEN seront également présentées.

Cachin F, J Nucl Med. 2014 Jan;55(1):15-22. doi: 10.2967/jnumed.113.123554.
Viallard C Eur J Dermatol. 2015 Jan-Feb;25(1):29-35. doi: 10.1684/ejd.2014.2481.
Viallard C. Oncotarget. 2016 Mar 15;7(11):12927-36. doi: 10.18632/oncotarget.7340
Rbah-Vidal L, Neoplasia. 2016 Dec 14;19(1):17-27. doi: 10.1016/j.neo.2016.11.001

conférence Martin Dutertre

The 29 November 2016 at 11:00.

Invitation : Aksam Merched – Mircade U 1035

Mardi 29 novembre à 11 h
Salle de conférences IBGC, site de Carreire zone sud, université de Bordeaux

Martin Dutertre
Institut Curie, UMR 3348 CNRS, Team « RNA biology linked to DNA damage », Orsay, France.

« Alternative splicing and polyadenylation in tumor progression and drug response »

It is now well established that gene expression mis-regulation in cancer occurs at many steps beyond transcription initiation, especially pre-messenger RNA splicing and miRNA-mediated regulations. Firstly, the seminar will illustrate that gene expression can be controlled quantitatively at the level of transcription elongation, as well as the efficiency of pre-mRNA maturation (e.g., splicing). Secondly, qualitative regulation is not mediated only by alternative splicing, but also by alternative promoters and alternative polyadenylation. In particular, I will describe how genome-wide approaches reveal the widespread involvement of a novel mechanism of gene regulation involving alternative last exons (also called intronic polyadenylation) in two processes: tumor cell metastasis and response to genotoxic drugs.

Conference Robert Ballottii

The 24 November 2016 from 11:00 to 17:00.

“Melanoma Initiating Cells, Senescence and Resistance: MITF Takes the Central Stage”

Robert Ballotti Inserm U1065, est invité par Pr taieb, pour nous cette conférence, salle de conférences de l’IBGC, site de Carreire zone sud, université de Bordeaux.

Among several hypotheses that might explain the resistance of melanoma to current therapies, one of the trendiest
suggests the existence of a poorly differentiated melanoma cell population that would also account for the well
recognized melanoma heterogeneity and invasiveness. This population, which displays an increase in mesenchymal
and stemness phenotypes, can be referred as Melanoma Initiating Cells (MIC). Previous works, including ours,
identified a low-MITF population endowed with all the properties of MIC, but in the absence of surface marker a full
characterization of this population was not possible.
To overcome this hurdle, we engineered, using homologous recombination, a melanoma cell model expressing a
MCherry flag upstream the exon 1 of the M-MITF. Using these cells, we have been able to isolate live LowMCherry/low-MITF
cells and to confirm their high tumorigenic potential, as well as their resistance to BRAF inhibitors.
DNA microarray analysis of Low-Mcherry vs High Mcherry allowed us to identify a repertoire of genes overexpressed in
the MIC that is different from that found in after MITF silencing. Among these genes several surface markers were
identified and we focused our attention on 2 of them; NGFR/CD271 that was already associated with MIC and ITGBL1 a
poorly studied member of integrin family.
Finally, preliminary analysis of the histone methylation/acetylation marks in Low-MITF vs High-MITF cells involves
epigenetic regulation in the control of the phenotypic switch between MIC and their differentiated progeny.
In summary, our data brought new insight into molecular mechanisms controlling melanoma cell plasticity,
tumorigenicity and resistance to drugs. Further investigations, will allow evaluating the importance these surface
markers and epigenetic modifications in melanoma treatment.

Conférence Francoise Pflumio

The 22 November 2016 from 11:00 to 15:00.

"Interactions between T-ALL and the BM microenvironment influence the leukemic development and the resistance to certain drugs"

Francoise Pflumio , CEA - Laboratoire des cellules Souches Hématopoïétiques et des Leucémies – LSHL
Salle de conférences de l’IBGC, site de Carreire zone sud, université de Bordeaux

T-cell acute lymphoblastic leukemia (T-ALL) is a T-cell progenitor malignancy, which mainly
affects children and young adults. In T-ALL development, leukemic cells home to various
bone marrow (BM) sites that include adipocyte-poor (red marrow) and adipocyte-rich (yellow
marrow) niches. Using xenografts of human and mouse T-ALL, we explored the impact of
these distinct BM sites on leukemic cells. We demonstrate that T-ALL cells invade all studied
BM sites but with different kinetics depending on those sites. T-ALL cells also displayed BMniche
specific characteristics in terms of cell surface phenotype, metabolism, cell cycle
progression albeit genomic abnormalities were similar wherever the T-ALL cells were isolated
from. Overall, our current results demonstrate that distinct BM sites differentially orchestrate
T-ALL development and during my talk I will also show how such BM niches may participate
into chemo-resistance.

thèse Emilie Indersie. Equipe MiRCaDe

The 18 November 2016 at 14:00.

Soutenance de thèse en vue de l'obtention du doctorat ne biologie cellulaire et physiopathologie.
"Nouveau modèle d'étude de l'hépatoblastome in vivo et identification de microARNs régulateurs de la béta-catenine" présentée par Emilie INDERSIE.
Composition du jury :
M. DOIGNON François, Professeur, Université de Bordeaux,
Mme ESPINOS-PARROU Estelle, Professeur, Université de Toulouse, Rapporteur,
M. GROSSET Christophe, Directeur de recherche, INSERM Bordeaux, Directeur de thèse,
Mme PERRET Christine, Directrice de recherche, Université Paris-Descartes, Rapporteur.

IMPORTANT !

[FR] Les chefs d’équipe sont responsables de l’organisation des réunions.

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