Valéria NAIM

CNRS UMR 9019 Paris-Saclay

Intégrité du génome et cancer

Gustave Roussy, Villejuif

"Understanding genome instability from S-phase to mitosis"

contact : Eric JULIEN (Inserm/CNRS)

Replication stress resulting from slowing or stalling of DNA replication forks is a major driver of genome instability during cancer initiation and progression. DNA replication can be challenged as a consequence of oncogene activation or by agents that interfere with DNA synthesis, such as the ones used in chemotherapy. To accomplish genome duplication and prevent chromosomal instability, cells have evolved mechanisms that protect, stabilize and/or restart replication forks while delaying cell cycle progression, which avoids entering mitosis with under-replicated DNA. Over the last years, however, work from several laboratories including ours has shown that cells can progress into mitosis with under-replicated DNA. This led to the identification of mechanisms, mediated by the Fanconi anemia (FA) and Homologous Recombination (HR) repair pathways, that promote post-replication repair and rescue of under-replicated DNA in mitosis, allowing cells to divide and continue proliferating. I will discuss how these findings have advanced our understanding of the link between replication stress and genome instability; I will present a molecular pathway that connects mitochondrial stress and functions of FA proteins in genome maintenance; finally, I will show that mechanisms involved in mitotic rescue of under-replicated DNA may represent promising targets to selectively kill cancer cells that sustain intrinsically high levels of replication stress.

Leila AKKARI

Division of Tumor Biology & Immunology, Oncode Institute.

Cancer Genomics Center Consortium

Netherlands Cancer Institute (NKI), Amsterdam

"Dissecting and Rewiring Immune Cell Heterogeneity in the Cancer Ecosystem: Myeloid Cells at Play"

contact : Nathalie Bonnefoy (Inserm)

Leila Akkari, PhD is Assistant Professor and Junior Group Leader at the Netherlands Cancer Institute in Amsterdam. In 2019, she was nominated Junior Member of the Oncode Institute. After an MSc between Montpellier (France) and Manchester (UK), she performed her PhD studies in Cell Biology at the Institute of Molecular Genetics of Montpellier, CNRS - French National Research Center, France, and completed her postdoctoral training in cancer biology, immunology and genetics, first at the Memorial Sloan Kettering Cancer Center in New York City, USA, and then at the Ludwig Cancer Center in Lausanne, Switzerland. In 2017 she joined the Netherlands Cancer Institute in Amsterdam, where she established her research laboratory. Since early on in her scientific career, she has been interested in understanding the complex interactions between cancer cells and normal cells within tumors and she works towards elucidating how external signals regulate cancer malignancy. Research in her group focuses on the role of immune cells in tumor maintenance and therapeutic resistance in brain and liver cancer, in order to harness these cells in personalized anti-cancer treatments.She is recipient of prestigious personal research grants, such as the Vidi Research Grant from the Dutch Science Research Council (NWO) in 2020 and three research grants from the Dutch Cancer Society (KWF), including the Young Investigator Grant, Bas Mulder Award in 2017. In 2020, she was selected by the renowned life sciences organization European Molecular Biology Organization (EMBO) for their Young Investigator Program. In 2022, she is leading a multi-million euros consortium to target brain cancer with different immunotherapies and novel nanocarriers (NWO).

 

Attention ! séminaire décalé au 09 juin 14h.

Rafael J. Argüello

Centre d'Immunologie de Marseille-Luminy (CMIL), CNRS-INSERM, Université Aix-Marseille

"One Cell At a Time : A Change of Perspective for metabolic Studies"

contact : Laurent Le Cam (Inserm)

Dans le cadre des séminaires hebdomadaires du LabEx MAbImprove, nous vous rappelons que le prochain séminaire externe aura lieu mercredi 19 avril à 9h30 à Tours (salle TO Conf 2 - Fac de Médecine) et retransmis en visioconférence à Montpellier (salle de conférence de l'IRCM). Exceptionnellement, nous assisterons à deux présentations successives. Invités par Lucie Pellissier, Clive R Bramham - Professor, Head of Neuroscience Research Group, Department of Biomedicine, University of Bergen, Norway - Molecular Control of Synaptic Plasticity, nous présentera ses travaux sur le thème "The Arc of Synaptic Memory: From Hub Protein to Retroviral-like Capsid" et Antonino Cattaneo - Professor of Neurobiology at the Scuola Normale Superiore (Pisa), European Brain Research Institute Roma, and also Director of the Biology Lab Bio@SnS nous présentera ses travaux sur un thème dont le titre vous sera communiqué ultérieurement.   Abstract ( Clive R Bramham) The immediate early gene, Arc, is a pivotal regulator of synaptic plasticity, memory, and cognitive flexibility. But what is Arc protein?  How does it work? Inside the neuron, Arc is a protein interaction hub and dynamic regulator of intracellular signaling in synaptic plasticity. In remarkable contrast, Arc can also self-assemble into retrovirus-like capsids that are released in extracellular vesicles and capable of intercellular transfer of RNA. Elucidation of the molecular basis of Arc hub and capsid functions, and the relationship between them, is vital for progress. The talk will present recent findings on Arc molecular structure-function regulation of oligomerization, and synaptic function in neurons. A major goal is to develop new tools for probing Arc function. To this end, we are evaluating anti-Arc nanobodies, selected from immunized Alpaca, for various applications.  The bacterially expressed, purified nanobodies bind to the retroviral homology capsid domain of Arc with high-affinity.  Crystal structure analysis shows that one of the nanobodies (Arc Nb-H11) binds to the ligand binding pocket of the capsid domain, important for Arc protein-protein interactions and signaling. Arc Nb-H11 expressed as intrabody in HEK 293 cells also binds selective to the capsid domain and allows immunoprecipitation of full-length Arc. 

MATTHIAS DROSTEN (ATTENTION Séminaire décalé au vendredi 02 Juin à 14h)

Centro de Investigación del Cáncer (CIC) and Instituto de Biología Molecular y Celular del Cáncer (IBMCC), CSIC-USAL, Salamanca, Spain

"Targeting RAS signaling in lung cancer"

contact : Antonio Maraver (Inserm) -ATTENTION Séminaire décalé au vendredi 02 Juin à 14h

KRAS oncogenes have been identified in a quarter of all human lung tumors. Recently, several inhibitors were developed that target specific mutant KRAS isoforms and two of them, directed against the KRAS G12C oncoprotein, have just been approved. However, most patients develop resistance against these inhibitors and no actual survival benefits have been observed in clinical trials. Thus, it is urgently required to identify novel therapeutic options applicable to most if not all patients with KRAS-mutant tumors. I will discuss what we have learned from genetically engineered mouse models about the development of resistance to KRAS inhibition. Moreover, I will present novel insights into the mechanisms of KRAS signaling in lung cancer and how a better understanding of KRAS signaling may help to overcome resistance to targeting either KRAS itself or its MAPK effector pathway.

SABINE COLNOT

Centre de Recherche des Cordeliers, INSERM UMRS1138, Paris

"Beta-catenin signaling, metabolism and epigenetics: a node for theranostics in primary liver cancers"

contact : Florence Cammas (Inserm/CNRS)

Publié le 06/02/2023Offer: The laboratory of Dr Nathalie Bonnefoy, Immunity and Cancer team, at the research cancer instituteof Montpellier (IRCM, INSERM U1194: https://www.ircm.fr) is looking for a full-time postdoctoral researchfellow to take on an exciting highly translational project to innovate in anti-cancer RAN based vaccine in thecontext of a European consortium project. The position is offered for 24 months with a possible reconduction for 1 year; selected candidate will workunder the supervision of Dr Julien Faget.Keywords: Neutrophil, lung cancer, immunotherapy, single-cell multi-omics, epigenetics, image masscytometry, genetic engineered mouse models  More...

Publié le 06/02/2023Offer: The laboratory of Dr Nathalie Bonnefoy, Immunity and Cancer team, at the research cancerinstitute of Montpellier (IRCM, INSERM U1194: https://www.ircm.fr) is looking for a full-timepostdoctoral research fellow to take on an exciting highly translational project to decipher tumorpromoting neutrophils biogenesis in non-small cell lung cancer patients and mouse models.The position is offered for 24 months with a possible reconduction for 1 year; selected candidate willwork under the supervision of Dr Julien Faget.Keywords: Neutrophil, lung cancer, immunotherapy, single-cell multi-omics, epigenetics, image masscytometry, genetic engineered mouse models  More...

Eric Julien, research director at IRCM - Institut de Recherche en Cancérologie de Montpellier and his team received financial support from the @laliguecancer of the Pyrénées-Orientales for the early detection and treatment of aggressive prostate cancer.Thanks for their financial support ?  En savoir plus : https://www.lindependant.fr/2022/11/30/pyrenees-orientales-bientot-un-depistage-precoce-des-cancers-de-la-prostate-agressifs-grace-aux-dons-locaux-10835512.php 

The fluorescence module of the slide scanner is installed!It is currently being validated by #MRI_Montpellier before being opened to the scientific community.Thank you to the Rotary clubs for their support of cancer research at the #IRCM and the #ICM