Conférence | Comment l'environnement social et les déterminants sociaux influencent le risque de cancer, sa prise en charge et son évolution | Dr Sébastien Lamy (CERPOP/IUCT)
2023-04-21 11:00 - 12:00 (Europe/Paris) | Salle Cazaux + Visio Teams
Lien vers la visioconférence

Workshop axe 2 "RNA & cancer"
2023-05-12 | Amphithéâtre IUCT-O

Conférence | Understanding and predicting the role of the immune microenvironment in lung adenocarcinoma | Dr Michaël Kammer
2023-06-02 11:00 - 12:00 | Salle Cazaux + Visio Teams
Lien vers la retransmission MS Teams

Conférence | Metabolic plasticity in ovarian cancer: a new therapeutic opportunity? | Pr Francesc Viñals
2023-06-09 11:00 - 12:00 | Salle Cazaux + Visio Teams

Conférence | Multimodal data integration for genetic diseases | Dr Anaïs Baudot
2023-06-16 11:00 - 12:00 | Salle Cazaux + Visio Teams

Conférence | Multiscale in silico modeling of life | Dr David Simoncini et Dr Sylvain Cussat-Blanc
2023-06-23 11:00 - 12:00 | Salle Cazaux + Visio Teams
Lien vers la retransmission vidéo sur MS Teams

Conférence | Self-organizing principles driving tumor stemness and hierarchy | Carlos Pérez-González (Institut Curie)
2023-06-28 13:30 - 14:30 | Salle Cazaux + Visio Teams
Colorectal tumors are heterogeneous and hierarchical. Tumor growth relies on the proliferation of cancer stem cells, which constantly produce non-proliferative differentiated cells that eventually die. Despite this hierarchy, treatments targeting cancer stem cells often fail at eradicating the tumor, because the remaining cancer cells dedifferentiate to replenish the stem cell pool. It is thus crucial to understand which factors compose the tumor stem cell niche to induce cancer stemness. While most research focuses on niche factors produced by the stroma, we studied the appearance of stem cells in tumor organoids cultured in the absence of niche factors. In these minimal conditions, stem cells spontaneously appear at the center of the organoid after 3 days in culture. Physical confinement of the organoid boosts the appearance of stem cells, showing that stemness can be mechanically induced by cell crowding. Furthermore, while small organoids mostly contain cancer stem cells after 5 days of culture, large organoids position the stem cell niche at the organoid edge and develop a differentiated area in the center. These organoids establish a functional hierarchy: stem cells proliferate at the edge, migrate towards the organoid center, differentiate, and die. This spatial distribution of cell types and functions is strikingly similar to that observed in real tumors. Our results show that cancer cells have an intrinsic ability to generate a stem cell niche in the absence of external signals and that there is a critical size to establish a functional hierarchy. Further experiments will reveal the molecular mechanisms governing these self-organizing principles, as well as their contribution to tumor progression.
References:
Pérez-González C*, Ceada G* et al. Mechanical compartmentalization of the intestinal organoid enables crypt folding and collective cell migration. Nat Cell Biol 23, 745–757 (2021).
Barbazan J*, Pérez-González C* et al. Cancer-associated fibroblasts actively compress cancer cells and modulate mechanotransduction. bioRxiv 2021.04.05.438443 (2021).
Pérez-González C*, Alert R* et al. Active wetting of epithelial tissues. Nat. Phys. 15, 79–88 (2019).

Lien vers la retransmission MS Teams

Conférence | Mechanical forces and microenvironment heterogeneity promote leukemic stem cell resistance | Dr Sylvain Lefort | CRCL, Lyon
2023-09-22 11:00 - 12:00 | Salle Cazaux + Visio Teams
Lien vers la visioconférence

Abstract :
In myeloid leukaemias, the rapid clonal expansion of leukemic cells in the bone marrow leads to alterations of microenvironment properties, and reduction of the overall availability for each cell type in the constrained space of the medullar niche. In addition, bone marrow fibrosis that often occurs in myeloid leukemias induces physical modifications of the microenvironment. Reciprocally, the leukemic niche through a symmetrical mechanic response can also affect the intrinsic stiffness of leukemic cells. Therefore, our goal is to understand how leukemic bone marrow microenvironment can support leukemic progression or alter treatment response in myeloid malignancies. For this purpose, we use a standardized 3D human co-culture model, which allows maintenance of hematopoietic stem cells capacities, to track CML leukemic stem cells dormancy upon treatment. In addition, we have identified that resistant AML cells harbors different intrinsic rigidities and mechanotransduction pathways activation compared to sensitive cells. Our current strategy includes study of the interplay between leukemic cells and extracellular matrices of different natures (composition and stiffness) and usage of a soft cell confinement system.
Selected Publications:
– Voeltzel T*, Fossard G, Degaud M, Geistlich K, Gadot N, Jeanpierre S, Mickaelian I, Brevet M, Anginot A, Le Bousse-Kerdiles MC, Trichet V, Lefort S*, Maguer-Satta V*. A minimal standardized human bone marrow microphysiological system to assess resident cell behavior during normal and pathological processes. Biomaterials Science. 2022 Jan 18;10(2):485-498.
– Lefort S, El-Naggar A, Tan S, Colborne S, Negri GL, Pellacani D, Hirst M, Gusterson B, Morin GB, Sorensen PH, Eaves CJ. De novo and cell lines models of human mammary cell transformation reveal an essential role for Yb-1 in multiple stages of human breast cancer. Cell Death Differ. 2022 Jan; 29(1):54-64.
– Jeanpierre S, Arizkane K, Thongjuea S, Grockowiak E, Geistlich K, Barral L, Voeltzel T, Guillemin A, Gonin-Giraud S, Gandrillon O, Nicolini FE, Mead A, Maguer-Satta V*, Lefort S*. The quiescent fraction of chronic myeloid leukemic stem cells depends on BMPR1B, Stat3 and BMP4-niche signals to persist in patients in remission. Haematologica. 2021 Jan 1 ;106(1) :111-122.
– Prunet A, Lefort S, Delanoë-Ayari H, Laperrousaz B, Simon G, Saci S, Argoul F, Guyot B, Rieu J-P, Gobert S*, Maguer-Satta V*, Rivière C*. Development of a soft cell confiner to decipher the impact of mechanical stimuli on cells. Lab Chip. 2020 Nov 7 ;20(21) :4016-4030
– Bulaeva E, Pellacani D, Nakamichi N, Hammond C.A, Beer P.A, Lorzadeh A, Moksa M, Carles A, Bilenky M, Lefort S, Shu J, Wilhelm B.T, Weng A.P, Hirst M, Eaves C.J. MYC-induced human acute myeloid leukemia requires a continuing IL3/GM-CSF co-stimulus. Blood. Dec 10 ;136(24) :2764-2773.
– Lefort S*, Balani S, Pellacani D, Guyot B, Gorski SM, Maguer-Satta V, Eaves CJ. Monitoring autophagy heterogeneity in normal and de novo transformants of human mammary cells. Sci Rep. 2020 Nov 20 ;10(1) :20266
– Lefort S*, Tan S, Balani S, Rafn B, Hirst M, Eaves CJ. Initiation of human mammary cell tumorigenesis by mutant KRAS requires YAP inactivation. Oncogene. 2019 Nov 26.
– Voeltzel T, Flores-Violante M, Zylbersztejn F, Lefort S, Billandon M, Jeanpierre S, Joly S, Fossard G, Milenkov M, Mazurier F, Nehme A, Belhabri A, Paubelle E, Thomas X, Michallet M, Louache F, Nicolini FE, Caron de Fromentel C, Maguer-Satta V. A new signaling cascade linking BMP4, BMPR1A, ΔNp73 and NANOG impacts on stem-like human cell properties and patient outcome. Cell Death Dis. 2018 Sep 27;9(10):1011.
– Lefort S, Thuleau A, Kieffer Y, Sirven P, Bieche I, Marangoni E, Vincent-Salomon A, Mechta-Grigoriou F. CXCR4 inhibitors could benefit to HER2 but not to triple-negative breast cancers patients. Oncogene 2017 Mar 2;36(9):1211-1222. doi: 10.1038.
– Nguyen LV*, Pellacani D*, Lefort S, Kannan N, Osako T, Makarem M, Cox CL, Kennedy W, Beer P, Carles A, Moksa M, Bilenky M, Balani S, Babovic S, Sun I, Rosin M, Aparicio S, Hirst M, Eaves CJ. Barcoding reveals complex clonal dynamics of de novo transformed human mammary cells. Nature. 2015 Dec 10; ;528(7581):267-71.
– Lefort S*, Joffre C*, Kieffer Y, Givel AM, Bourachot B, Zago G, Bieche I, Dubois T, Meseure D, Vincent-Salomon A, Camonis J, Mechta-Grigoriou F. Inhibition of autophagy as a new means of improving chemotherapy efficiency in high-LC3B triple-negative breast cancers. Autophagy. 2014;10(12):2122-42.
Mini Bio:
Tout au long de mes travaux de recherche, j’ai cherché à identifier des mécanismes intrinsèques et extrinsèques essentiels à l’homéostasie, à l’initiation et la progression tumorale. Ainsi durant mon PhD (2005-2009), j’ai identifié des mécanismes consécutifs à l’infection par KSHV permettant l’établissement de la pathologie et de la tumorigénèse. J’ai ensuite rejoint l’Institut Curie (2009-2013), où mes travaux ont permis d’identifier des cibles thérapeutiques tumorales ou microenvironnementales spécifiques de sous−types de cancer du sein. Au sein du laboratoire Terry Fox (2014-2017), mes travaux sur les cellules souches et progénitrices mammaires humaines ont permis d’étudier le rôle de plusieurs déterminants moléculaires, tels que YB−1 et YAP, impliqués dans l’initiation tumorale. Ayant rejoint le CRCL en 2017, je m’intéresse dorénavant au rôle des contraintes mécaniques, via les éléments mécanosenseurs BMP et YAP, dans le maintien des cellules souches hématopoïétiques et leucémiques via leur interaction avec leur microenvironnement.

Workshop Post-doctorants
2023-10-05 | Amphithéâtre IUCT-O
Plus d’informaitons : https://www.crct-inserm.fr/en/ys2c_gso/

Soutenance de thèse de Sebastian Castillo (Equipe Signather)
2023-10-09 09:00 - 11:00 | Salle Cazaux + Visio Teams
Intitulé de la thèse :
Regulation of the ERK/MAPK signaling pathway by the small GTPase RHOB in non-small-cell lung cancer

Pour suivre la soutenance de thèse à distance, cliquez ici.

Conférence : BMP2 and BMP7 cooperate with H3.3K27M to promote quiescence and invasiveness in pediatric diffuse midline gliomas | Marie Castets, CRCL
2023-10-13 11:40 - 12:10 | Salle Cazaux + Visio Teams
Important : reportée de 11h40 à 12h10
Pour suivre la conférence à distance, cliquez ici.
Abstract :
Pediatric diffuse midline gliomas (pDMG) are an aggressive type of childhood cancer with a fatal outcome. Their major epigenetic determinism has become clear, notably with the identification of K27M mutations in histone H3. However, the synergistic oncogenic mechanisms that induce and maintain tumor cell phenotype have yet to be deciphered.
In 20 to 30% of cases, these tumors have an altered BMP signaling pathway with an oncogenic mutation on the BMP type I receptor ALK2, encoded by ACVR1. However, the potential impact of the BMP pathway in tumors non-mutated for ACVR1 is less clear. By integrating bulk, single-cell and spatial transcriptomic data, we show here that the BMP signaling pathway is activated at similar levels between ACVR1 wild type and mutant tumors and identify BMP2 and BMP7 as putative activators of the pathway in a specific subpopulation of cells. By using both pediatric isogenic glioma lines genetically modified to overexpress H3.3K27M and patients-derived DIPG cell lines, we demonstrate that BMP2/7 synergizes with H3.3K27M to induce a transcriptomic rewiring associated with a quiescent but invasive cell state. These data suggest a generic oncogenic role for the BMP pathway in gliomagenesis of pDMG and pave the way for specific targeting of downstream effectors mediating the BMP/K27M crosstalk.

Publication shortlist :
Modeling the next-generation of fusion-negative rhabdomyosarcoma 3D-organoids to predict effective drug combinations: a proof-of-concept on cell death inducers. Clara Savary, Paul Huchedé, Léa Luciana, Arthur Tourbez, Clémence Deligne, Cécile Picard, Thomas Diot, Claire Coquet, Nina Meynard, Marion Le Grand, Laurie Tonon, Nicolas Gadot, Cyril Degletagne, Sophie Léon, Valéry Attignon, Alexandra Bomane, Isabelle Rochet, Kevin Müller, Virginie Mournetas, Christophe Bergeron, Paul Rinaudo, Aurélie Dutour, Martine Cordier-Bussat, Frédérique Dijoud, Nadège Corradini, View ORCID ProfileDelphine Maucort-Boulch, Eddy Pasquier, View ORCID ProfileJean-Yves Blay, Marie Castets*, Laura Broutier*. In revision, Cell Reports Medicine. Available on Biorxiv.
BMP2 and BMP7 cooperate with H3.3K27M to promote quiescence and invasiveness in pediatric diffuse midline gliomas. Paul Huchedé, Swann Meyer, Clément Berthelot, Maud Hamadou, Adrien Bertrand-Chapel, Andria Rakotomalala, Line Manceau, Julia Tomine, Nicolas Lespinasse, Paul Lewandowski, Martine Cordier-Bussat, Laura Broutier, Aurélie Dutour, Isabelle Rochet, Jean-Yves Blay, Cyril Degletagne, Valéry Attignon, Angel Montero-Carcaboso, Marion Le Grand, Eddy Pasquier, Alexandre Vasiljevic, Pascale Gilardi-Hebenstreit, Samuel Meignan, Pierre Leblond, Vanessa Ribes, Erika Cosset, Marie Castets. eLife, in press. Available on Biorxiv.
The TLR3 L412F polymorphism prevents TLR3-mediated tumor cell death induction in pediatric sarcomas. Bisaccia J, Meyer S, Bertrand-Chapel A, Hecquet Q, Barbet V, Kaniewski B, Léon S, Gadot N, Rochet I, Fajnorova I, Leblond P, Cordier-Bussat M, Corradini N, Vasiljevic A, Billaud M, Picard C, Broutier L, Gallerne C, Dutour A, Blay JY, Castets M. Cell Death Discov. 2023 Jul 7;9(1):230. doi: 10.1038/s41420-023-01513-y. PMID: 37414800
Holistic pediatric oncology: towards a second Copernican revolution. André N, Castets M, Pasquier E, Mehlen P. Trends Cancer. 2023 Sep;9(9):693-696.
The Intricate Epigenetic and Transcriptional Alterations in Pediatric High-Grade Gliomas: Targeting the Crosstalk as the Oncogenic Achilles’ Heel. Huchedé P, Leblond P, Castets M. Biomedicines. 2022 Jun 3;10(6):1311. doi: 10.3390/biomedicines10061311. PMID: 35740334
The Ectodysplasin receptor EDAR acts as a tumor suppressor in melanoma by conditionally inducing cell death. Vial J, Royet A, Cassier P, Tortereau A, Dinvaut S, Maillet D, Gratadou-Hupon L, Creveaux M, Sadier A, Tondeur G, Léon S, Depaepe L, Pantalacci S, de la Fouchardière A, Micheau O, Dalle S, Laudet V, Mehlen P, Castets M. Cell Death Differ. 2019 Mar;26(3):443-454. doi: 10.1038/s41418-018-0128-1. Epub 2018 May 31. PMID: 29855541
Mini Bio
Marie Castets, PhD
Chef de l’équipe « Mort cellulaire et cancers pédiatriques » au Centre de Recherche en cancérologie de Lyon, CRCL, Centre Léon Bérard, Lyon, elle est aussi à l’origine du réseau national React4Kids lancé en 2018, et qui réunit actuellement l’ensemble des scientifiques français développant des axes de recherche fondamentale et translationnelle en cancérologie pédiatrique.
« Face à la complexité du cancer, il n’y a qu’en mutualisant nos expertises et nos outils que nous parviendrons à améliorer de manière significative la prise en charge des patients. Et si cette collaboration doit évidemment se faire au niveau international, il convient de s’appuyer sur une forte structuration nationale pour avancer de manière efficace dans la compréhension des mécanismes moléculaires impliqués dans les cancers pédiatriques. C’est l’objectif du réseau national de recherche fondamentale et translationnelle React4Kids, lancé en 2018 avec une dizaine de chercheurs et qui compte aujourd’hui plus de 380 membres. »
Elle pilote également depuis 2020 la plateforme Share4Kids, dont l’objectif est de mettre à disposition de la communauté scientifique des données multi-omiques de qualité en open-access sur les cancers des enfants.

Conférence | Insights into the disruption of gene regulatory programs in cancers | Dr Anthony Mathelier
2023-10-20 11:00 - 12:00 | Salle Cazaux + Visio Teams
Pour suivre la conférence à distance, cliquez ici.
Abstract:
Most cancer somatic alterations occur in the noncoding portion of the human genome, which contains important cis-regulatory regions acting as genetic switches to ensure gene expression occurs at correct times and intensities in correct tissues. However, the identification of critical noncoding cancer driver events has been mostly limited to a few examples with high recurrence or high functional impact. Transcription factors (TFs) are key proteins binding to cis-regulatory regions at their TF binding sites to modulate the rate of gene transcription. As cancer is a disease of disrupted cellular regulation, it is critical to analyze these regions to highlight patient somatic mutations and epigenetic modifications altering the gene regulatory program of the cells. In this talk, I will present our recent works on the interplay between TF binding, somatic mutations, and DNA methylation alteration that shifts the gene regulatory program in patients cancer cells.

Séminaire Jeunes Chercheurs du Labex Toucan
2023-10-26 14:00 - 17:00 | Amphithéâtre IUCT-O

Workshop axe 3 Microenvironnement tumoral et métabolisme
2023-11-09 09:00 - 13:00 | Amphithéâtre IUCT-O
Cliquez ici pour découvrir les abstracts des intervenants.

Conférence : Patient trajectories derived from synchronic clinical datasets | Andrei Zinovyev, Evotec
2023-11-17 11:00 - 12:00 | Salle Cazaux + Visio Teams
Pour suivre la conférence à distance, cliquez ici.
Abstract:
The concept of patient trajectory is important in understanding a disease as a dynamic process that evolves over time. Evaluating patient trajectories typically involves longitudinal (diachronic) datasets, which are still relatively scarce and expensive. Drawing from the concepts of pseudotime and the ergodic principle in single-cell data science, we recently introduced a methodology for quantifying hypothetical stereotypical patient trajectories from synchronic (snapshot) clinical datasets. These trajectories characterize the landscape of all possible disease conditions, illustrating how a specific disease state develops along stereotypical routes, marked by « points of no return » and « final states » such as lethal or recovery states. We demonstrate how applying this methodology yields insights from extensive clinical datasets in cardiology and COPD, which can be used to enhance these diseases management.
Short bio:
Andrei Zinovyev has a background in computational biology and machine learning, focusing on developing new methods and algorithms for modeling and analyzing biological data. After completing a 3-year postdoc at the Institute des Hautes Études Scientifiques (the French counterpart of the Advanced Studies), he transitioned to the Institut Curie, where he co-founded the « Computational Systems Biology of Cancer » research group, which he co-led for 18 years. In 2019, Andrei got a chair at the Paris Artificial Intelligence Research Institute, focusing on the application of machine learning to multiomics and clinical data. In 2022, he made the switch to industrial research in the role of Principal Scientist at Evotec in Toulouse in the In silico R&D department.

WORKSHOP : Clinical applications of PI3K inhibitors
2024-01-11 09:30 - 15:45 | Amphithéâtre IUCT-O + MS Teams
Speakers:
Michael LAHN, Mariona GRAUPERA, Emilio HIRSCH+ others
Lien Teams :
Programme

Formation qPCR
2025-01-23 09:30 - 16:30 | Salle Cazaux
Organisé par Carine Valle et Emeline Sarot
carine.valle@inserm.fr / emeline.sarot@inserm.fr

Stand Société Selleck Chemicals
2025-02-06 09:00 - 13:00 | Espace détente 1er étage
Présentation de produits et offres
Intervenants : Esther Marque, Brian Donegan

Soutenance de thèse : Intérêt de l'ADN tumoral circulant dans la prise en charge de l'adénocarcinome pancréatique résécable - Charlotte Maulat, ImPACT/CHU Toulouse
2025-02-28 14:00 - 17:00 | salle du conseil de la faculté de médecine au 32 allées Jules Guesdes

Conférence - Anna Niarakis, CBI
2025-03-14 11:00 - 12:00 | Salle Cazaux
Dr Anna Niarakis is now a Full Professor of Computational Systems Biology at the University of Toulouse III-Paul Sabatier, affiliated with the Center of Integrative Biology and the Laboratory of Molecular, Cellular and Developmental Biology. She was previously an Associate Professor at the University of Evry, Paris Saclay, and an INRIA Saclay delegate.
She has a broad scientific background in Biochemistry, Biology, Pharmaceutical Technology and post-doctoral studies in Computational Systems Biology and Bioinformatics (ENS, Paris, Institut Gustave Roussy) with expertise in complex human diseases, especially autoimmune diseases. She is a co-leader of the Disease Maps consortium and leads the Working Group “ Building Immune Digital Twins”, supported by the Research Data Alliance.
Google scholar: https://scholar.google.ch/citations?user=bpOOfdMAAAAJ&hl=en
LinkedIn: https://www.linkedin.com/in/anna-niarakis-58535b3/

Séminaire technologique - Felipe Oliveira, Navinci
2025-03-20 10:00 - 11:00 | Salle Cazaux
Dr. Felipe Oliveira is a Field Application Specialist at Navinci; with over 10 years of experience in varying forms of proximity ligation assays. He completed his PhD in the lab of Prof. Masood Kamali-Moghaddam in 2018, where he developed and applied variations of proximity assays for detection of single biomarker, complex protein, as well as PTMs. He holds a PhD in molecular medicine and molecular tools development from Uppsala University and a BSc in molecular biology from Emory University.
Pour en savoir plus sur le séminaire technologique, cliquez ici

Séminaire - Pierre Cordelier, équipe ImPact
2025-03-28 11:00 - 12:00 | Salle Cazaux

Single cell Chromium FLEX : retours d'expériences du CRCT
2025-04-03 14:00 - 16:30 | Salle Cazaux
La plateforme de Génomique-Transcriptomique et la société 10x Genomics vous invitent le 3 avril de 14h à 16h30 en salle Cazaux au CRCT à un retour d’expériences sur des projets réalisés au CRCT avec la technologie single cell FLEX.
Cette approche permet de caractériser par séquençage la transcriptomique de cellules uniques à partir d’échantillons fixés ou FFPE.
Intervenants :
Pauline Gravelle (CRCT, Equipe NoLymIT)
Aymeric Zambiasi/Charlotte Dubucs (IUCT O, Anapath)
Coralie Cayron/Julie Guillermet (CRCT, Equipe SigDyn)
Abdelaziz Boual (10x Genomics)
Cecilia Korol (10x Genomics)
Inscription gratuite mais obligatoire

Séminaire | Elizabeth Moyal, équipe RADOPT
2025-04-10 13:30 - 14:30 | Salle Cazaux
En savoir plus sur l’équipe RADOPT, cliquez ici.

Conférence | Benoit Salomon, Infinity
2025-04-29 13:00 - 14:00 | Salle Cazaux

Séminaire Bioinformatique - Dr Miguel Ponce-de-Leon, Barcelona Supercomputing Center
2025-04-30 11:00 - 12:00 | Salle Cazaux
We will have the pleasure to host Dr Miguel Ponce-de-Leon from Barcelona Supercomputing Center speaking about:

Computational Systems Biology for Cancer Treatment: Bridging Scales to Understand Drug Synergies

Abstract: Understanding and overcoming drug resistance in cancer requires a systems-level perspective that spans molecular, cellular, and population scales. One promising strategy to counteract resistance is the use of drug combinations that act synergistically to enhance therapeutic efficacy while limiting adaptation. In this talk, I will present a suite of computational systems biology approaches that form a mechanistic, multiscale framework for studying drug synergies and resistance. In the first part of the presentation, I will introduce a multiscale modelling framework that connects intracellular signalling networks with spatially explicit agent-based models. Using in vitro experiments on the gastric adenocarcinoma cell line AGS, we developed a model to simulate the effects of kinase inhibitors—both individually and in combination—on cell proliferation and apoptosis. We calibrated the model parameters using time-course data from single-drug treatments. Remarkably, the model was able to reproduce the experimental dynamics observed under combinatorial treatments, despite not being trained on them. This result highlights the model’s predictive power and provides mechanistic insights into the emergence of drug synergies at the phenotypic level. To further investigate the molecular basis of these effects, we integrate transcriptomic data into genome-scale metabolic models using constraint-based approaches. This analysis reveals distinct metabolic shifts under combinatorial treatments, particularly in amino acid and polyamine biosynthesis, suggesting key metabolic vulnerabilities linked to drug synergy. By combining multi-omics data with mechanistic modelling, we aim to support the development of personalised combination therapies that exploit the systems-level complexity of tumour biology.

Miguel Ponce-de-Leon has been an established researcher at Alfonso Valencia’s Lab within the Barcelona Supercomputing Centre since 2021. He earned his bachelor’s in biophysics from Udelar and a master’s in bioinformatics from PEDECIBA in Uruguay. Dr. Ponce-de-Leon completed his PhD thesis on metabolic reconstruction and modelling to study endosymbiotic bacteria at Universidad Complutense de Madrid, under the guidance of Professors Francisco Montero and Juli Peretó. In 2017, he joined the Computational Biology Group at the Barcelona Supercomputing Centre as a postdoctoral researcher under the supervision of Professor Alfonso Valencia. From 2017 to 2020, Dr. Ponce-de-Leon specialised in computational systems biology and its applications to precision medicine. He pioneered novel multi-scale modelling approaches, integrating cell signalling and metabolic networks with agent-based models to study tumour growth and evolution towards drug resistance.

Workshop ARN & Cancer 2025
2025-05-15 | Amphithéâtre IUCT-O
3ème Workshop ARN & Cancer
En savoir +

MINI WORKSHOP | Lighting the fire: inflammasomes and pyroptosis in cancer and neurodegeneration
2025-05-21 10:00 - 12:30 | Salle Cazaux + Visio Teams
Toutes les informations :

Abstract:
Inflammasomes are intracellular multi-protein complexes that play essential functions in immunity against pathogens. Specifically, inflammasomes both promote a regulated form of cell death termed pyroptosis and trigger the release of the key inflammatory cytokines interleukin (IL)-1β and IL-18, two important processes in controlling microbial infections. Because of their involvement in various pathophysiological conditions, our understanding of inflammasomes has generated an ever-growing interest in the scientific and medical communities over the last 20 years. Yet, most of this knowledge comes either from the use of rodent models, which may lack the specific structural and functional characteristics of human inflammasomes, or from the use of immune cells, which express a wide range of inflammasomes but lack inflammasomes specifically enriched in non-immune cells.
In this context, I will discuss about novel findings on the crucial immune function of the human NLRP1 inflammasome, highly expressed in airway, skin and corneal epithelia, in response to a broad range of infections but also environmental threats that converge to a specific stress pathway, the ribotoxic stress response. Specifically I will adress our very recent findings that unexpectedely link dna damage and ribotoxic stress-induced nlrp1 inflammasome response upon chemotherapy and microbial genotoxin exposure.

Abstract:
Prokaryotic pore-forming toxins drive inflammasome activation and pyroptosis through K+-dependent activation of the canonical NLRP3/caspase-1/gasdermin D signaling axis. In this study, we hypothesized that perforin, a eukaryotic pore-forming protein released into the lytic synapse by antigen-specific cytotoxic T lymphocytes (CTLs) upon cognate antigen recognition, mimics the pro-pyroptotic activity of ancestral pore-forming toxins, complementing its role as a conduit for granzymes. Utilizing imaging and molecular approaches, we demonstrate that perforation of target cells upon CTL attack elicits swift K+ efflux followed by NLRP3-dependent activation of proinflammatory caspase-1 and its major substrate, the pyroptotic executioner gasdermin D (GSDMD). Acute target cell death upon CTL attack is gasdermin-dependent and demonstrates morphological and molecular features of pyroptosis, including pyroptotic body formation, cell bloating, plasma membrane rupture, and release of intracellular contents; by contrast, sustained interaction with CTLs unmasks a delayed apoptotic phenotype in the remaining target cells. Perforation of target cells by soluble perforin is sufficient to trigger rapid K+ efflux, caspase-1 activation, and pyroptosis. Our results reveal a novel mechanism for engagement of pyroptotic machinery upon CTL attack, in which perforin itself can autonomously engage programmed cell death (PCD), highlighting the complexity and diversity of the CTL lytic arsenal.

Abstract:
Pyroptosis is a highly inflammatory form of regulated cell death driven by pore-forming gasdermin (GSDM) proteins. Following proteolytic activation, GSDMs form oligomeric pores that promote plasma membrane rupture (PMR) and amplify the inflammatory response. Canonical pyroptosis is initiated by inflammasome complexes, which recruit and mature caspase-1 to activate GSDMD. Independently of the inflammasome, GSDME can transition apoptosis to pyroptosis following cleavage by caspase-3. A subset of HIV[+] patients experience progressive cognitive impairment and neurodegeneration (NeuroHIV) driven by infection of brain myeloid cells. However, the mechanisms which underlie neuronal injury remain uncertain. We hypothesized that the inflammasome-pyroptosis axis (IPA) in neurons directly mediates HIV-associated neurodegeneration. Examination of primary human neural cultures revealed GSDMD is restricted to glial cells, whereas neurons selectively express GSDME. Neurons exposed to HIV viral protein R (Vpr), an established NLRP3 inflammasome stimulus, showed substantial neurite retraction and PMR with activation of caspases-1, -3 and GSDME. Genetic knockdown of NLRP3, caspase-1, or GSDME significantly reduced neuronal PMR. Furthermore, caspase-1 inhibition limited caspase-3/GSDME cleavage and neurite degradation, suggesting that inflammasome signalling initiates neuronal pyroptosis. Direct activation of caspase-1 using an optogenetic approach verified these findings, resulting in rapid activation of the caspase-3/GSDME axis, PMR and cell death morphologically consistent with pyroptosis. Furthermore, analysis of cortical brain tissues from persons with NeuroHIV and in an associated macaque model (NeuroSIV) revealed GSDME cleavage and markers of neuronal pyroptosis. Our findings demonstrate neuronal IPA signalling with downstream GSDME activation can directly contribute to HIV-associated neurodegeneration.
Pour suivre le mini workshop à distance, cliquez ici.

Conférence | Jean Monlong, IRSD
2025-05-23 11:00 - 12:00 | Salle Cazaux
Bio:
Jean Monlong has been working with sequencing data for more than 10 years, first on transcriptomics as a master student in Barcelona at the Centre for Genomic Regulation with Roderic Guigo, then switching to genomics during his PhD at McGill University in Montreal with Guillaume Bourque. He then joined the University of California, Santa Cruz for his postdoc to work on variant calling with pangenomes in the group of Benedict Paten. Since 2023, Jean is a Chargé de Recherche INSERM at the Institut de Recherche en Santé Digestive (IRSD) where he continues using pangenomes and sequencing technologies to improve the analysis of human genomes and the functional interpretation of genomic variation.

Abstract:
Variant affecting more than 50 nucleotides, or structural variants, can have important functional impacts. They unfortunately tend to be understudied because of technical challenges hindering their detection. I will present two approaches to integrate those variants in genomic studies. The first uses pangenomes as augmented reference genome containing common variants (including structural variants). With this more complete reference, short sequencing reads are better analyzed, resulting in a larger number of structural variants that can be genotyped accurately. The second approach uses cost-efficient long read sequencing technology, such as Oxford Nanopore, to infer phased variants at unprecedented resolution.

Atelier Spinning CRCT - LORDIL | Découvrez comment transformer votre Vidéomicroscope en Confocal rapide !
2025-06-03 - 2025-06-05 | Pôle Technologique
