team
VERA PANCALDI

NetB(IO)² :

Network Biology for Immuno-oncology

 

THE SPECIFITIES

OF OUR RESEARCH AXIS

Our lab studies the relationship between patients and cancer, focusing on how the immune system and the tumour interact. We aim to improve therapies that exploit this interaction. Currently such therapies only work on some patients and, often, for a limited time before patients develop resistance against the therapy.
Our goal is to understand how variability in the patients, in the tumours, and in their interactions affects the efficacy of these therapies. We use computational approaches including data science, simulations, modeling and especially network theory.
Networks are a useful framework to represent systems in which relationships such as interactions or similarity between objects are important. All networks share some common properties and a vast literature exists on how to measure them. The beauty is that our understanding of one type of network can help us better understand a completely different one.
We apply network models to study such diverse systems as networks of patient-patient similarity, networks of interactions between different cell types in a tumour, and 3D interactions of genes in the nucleus.

In the same healthy organism, two cells of the same type, sharing the same DNA, can still display some variability, due to the organization of more than two meters of DNA in a tiny nucleus. These changes in DNA configuration impact the characteristics and behavior of the cells.

The important common factor characterising these systems is variability.
Variability pervades biological systems. On one side, the difference between patients is thwarting our successes in medicine and calls for personalised medicine approaches, especially in oncology. On the other side, there are many contexts within the body characterised by a heterogeneous mix of cell types; for example the gut, the bone marrow or the tissue surrounding a tumour. Complex relationships between cell types establish ‘ecological networks’ whose properties reflect the equilibria that define health against  disease.

 

The variety of cell types in the tumor and their relationships: 

Determining the cellular composition and organization of a tumour sample remains the priority in cancer research. Our team integrates omics data to estimate the proportions of different cell types and their spatial relationships in the tumor.

Simulating the complex interactions of these cells in our computers, both at the molecular and intercellular level, offers the possibility to study these systems in a multitude of scenarios. This is an excellent way to formulate new hypotheses and allows better use of our experimental resources.

Since 2020 we have launched collaborative projects with other CRCT teams with the co-supervision of 4 theses:

Rüçhan Ekren (Labex Toucan grant), with Ludovic Martinet. Study of T cell depletion mechanisms and NK cell biology in multiple myeloma, using single cell approaches on proteomic and transcriptomic (CITEseq) datasets (human or mouse).

Matthieu Genais (BSB doctoral school grant), with Bruno Segui. Artificial intelligence approaches to determine the impact of TNFa on the response to immune checkpoint inhibitors (ICB) in melanoma. Use of clinical, CITEseq and metabolomic data.

Alexis Hucteau (Labex Toucan grant), with J.E Sarry. Study of acute myeloid leukemia and specific metabolic resistances by combining RNAseq, DNA methylation, histone modifications, metabolic connections, epigenomics and reprogramming approaches.

Jacobo Solorzano (scholarship from Occitanie region and Fondation Toulouse Cancer Santé ), with Yvan Martineau and Corinne Bousquet. Translation and role of stromal cells (particularly CAFs) in the emergence of cancer cells activating the integrated stress response (ISR) in pancreatic cancers.

 

Computational Biology

Network Theory

Heterogeneity and Tumour Microenvironment

Immune System

Epigenomics

Spatial and single cell transcriptomics

Genome Architecture

Mathematical Models

research projects

THE TEAM’S
FOCUS

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SCIENTIFIC PRODUCTIONS

PUBLICATIONS 2022
Rouanet, Marie, Naima Hanoun, Hubert Lulka, Cindy Ferreira, Pierre Garcin, Martin Sramek, Godefroy Jacquemin, et al. “The Antitumoral Activity of TLR7 Ligands Is Corrupted by the Microenvironment of Pancreatic Tumors.” Molecular Therapy, 2022, S1525001622000181. https://doi.org/10.1016/j.ymthe.2022.01.018.
PUBLICATIONS 2021
Richart, Laia, Eleonora Lapi, Vera Pancaldi, Mirabai Cuenca-Ardura, Enrique Carrillo-de-Santa Pau, Miguel Madrid-Mencía, Hélène Neyret-Kahn, et al. “STAG2 Loss-of-Function Affects Short-Range Genomic Contacts and Modulates the Basal-Luminal Transcriptional Program of Bladder Cancer Cells.” Nucleic Acids Research 49, no. 19 (November 8, 2021): 11005–21. https://doi.org/10.1093/nar/gkab864.
Sabatier, Marie, Emeline Boet, Sonia Zaghdoudi, Nathan Guiraud, Alexis Hucteau, Nathaniel Polley, Guillaume Cognet, et al. “Activation of Vitamin D Receptor Pathway Enhances Differentiating Capacity in Acute Myeloid Leukemia with Isocitrate Dehydrogenase Mutations.” Cancers 13, no. 20 (October 19, 2021): 5243. https://doi.org/10.3390/cancers13205243.
Cao, Kim-Anh Lê, Al J. Abadi, Emily F. Davis-Marcisak, Lauren Hsu, Arshi Arora, Alexis Coullomb, Atul Deshpande, et al. “Author Correction: Community-Wide Hackathons to Identify Central Themes in Single-Cell Multi-Omics.” Genome Biology 22, no. 1 (August 25, 2021): 246. https://doi.org/10.1186/s13059-021-02468-y.
Lê Cao, Kim-Anh, Al J. Abadi, Emily F. Davis-Marcisak, Lauren Hsu, Arshi Arora, Alexis Coullomb, Atul Deshpande, et al. “Community-Wide Hackathons to Identify Central Themes in Single-Cell Multi-Omics.” Genome Biology 22, no. 1 (August 5, 2021): 220. https://doi.org/10.1186/s13059-021-02433-9.
Coullomb, Alexis, and Vera Pancaldi. “Tysserand - Fast and Accurate Reconstruction of Spatial Networks from Bioimages.” Bioinformatics (Oxford, England), July 2, 2021, btab490. https://doi.org/10.1093/bioinformatics/btab490.
Courtot, Lilas, Elodie Bournique, Chrystelle Maric, Laure Guitton-Sert, Miguel Madrid-Mencía, Vera Pancaldi, Jean-Charles Cadoret, Jean-Sébastien Hoffmann, and Valérie Bergoglio. “Low Replicative Stress Triggers Cell-Type Specific Inheritable Advanced Replication Timing.” International Journal of Molecular Sciences 22, no. 9 (May 7, 2021). https://doi.org/10.3390/ijms22094959.
Stuani, Lucille, Marie Sabatier, Estelle Saland, Guillaume Cognet, Nathalie Poupin, Claudie Bosc, Florence A. Castelli, et al. “Mitochondrial Metabolism Supports Resistance to IDH Mutant Inhibitors in Acute Myeloid Leukemia.” The Journal of Experimental Medicine 218, no. 5 (May 3, 2021). https://doi.org/10.1084/jem.20200924.
Pancaldi, Vera. “Chromatin Network Analyses: Towards Structure-Function Relationships in Epigenomics.” Frontiers in Bioinformatics 1 (2021): 59. https://doi.org/10.3389/fbinf.2021.742216.
PUBLICATIONS 2020
Marku, Malvina, Nina Verstraete, Flavien Raynal, Miguel Madrid-Mencía, Marcin Domagala, Jean-Jacques Fournié, Loïc Ysebaert, Mary Poupot, and Vera Pancaldi. “Insights on TAM Formation from a Boolean Model of Macrophage Polarization Based on In Vitro Studies.” Cancers 12, no. 12 (December 7, 2020): 3664. https://doi.org/10.3390/cancers12123664.
Weulersse, Marianne, Assia Asrir, Andrea C. Pichler, Lea Lemaitre, Matthias Braun, Nadege Carrie, Marie-Veronique Joubert, et al. “Eomes-Dependent Loss of the Co-Activating Receptor CD226 Restrains CD8(+) T Cell Anti-Tumor Functions and Limits the Efficacy of Cancer Immunotherapy.” Immunity 53, no. 4 (October 13, 2020): 824-839.e10. https://doi.org/10.1016/j.immuni.2020.09.006.
Malod-Dognin, N, V Pancaldi, A Valencia, and N Pržulj. “Chromatin Network Markers of Leukemia.” Bioinformatics 36, no. Supplement_1 (July 1, 2020): i455–63. https://doi.org/10.1093/bioinformatics/btaa445.
Sánchez-Valle, Jon, Héctor Tejero, José María Fernández, David Juan, Beatriz Urda-García, Salvador Capella-Gutiérrez, Fátima Al-Shahrour, et al. “Interpreting Molecular Similarity between Patients as a Determinant of Disease Comorbidity Relationships.” Nature Communications 11, no. 1 (2020): 2854. https://doi.org/10.1038/s41467-020-16540-x.
Trama, Annalisa, Claudia Proto, Jennifer G. Whisenant, Valter Torri, Alessio Cortellini, Olivier Michielin, Fabrice Barlesi, et al. “Supporting Clinical Decision-Making during the SARS-CoV-2 Pandemic through a Global Research Commitment: The TERAVOLT Experience.” Cancer Cell 38, no. 5 (2020): 602–4. https://doi.org/10.1016/j.ccell.2020.10.002.
Garassino, Marina Chiara, Jennifer G Whisenant, Li-Ching Huang, Annalisa Trama, Valter Torri, Francesco Agustoni, Javier Baena, et al. “COVID-19 in Patients with Thoracic Malignancies (TERAVOLT): First Results of an International, Registry-Based, Cohort Study.” The Lancet Oncology 21, no. 7 (2020): 914–22. https://doi.org/10.1016/S1470-2045(20)30314-4.
Whisenant, Jennifer G., Annalisa Trama, Valter Torri, Alessandro De Toma, Giuseppe Viscardi, Alessio Cortellini, Olivier Michielin, et al. “TERAVOLT: Thoracic Cancers International COVID-19 Collaboration.” Cancer Cell 37, no. 6 (08 2020): 742–45. https://doi.org/10.1016/j.ccell.2020.05.008.
Madrid-Mencía, Miguel, Emanuele Raineri, Tran Bich Ngoc Cao, and Vera Pancaldi. “Using GARDEN-NET and ChAseR to Explore Human Haematopoietic 3D Chromatin Interaction Networks.” Nucleic Acids Research 48, no. 8 (07 2020): 4066–80. https://doi.org/10.1093/nar/gkaa159.
Gaudelet, Thomas, Noël Malod-Dognin, Jon Sánchez-Valle, Vera Pancaldi, Alfonso Valencia, and Nataša Pržulj. “Unveiling New Disease, Pathway, and Gene Associations via Multi-Scale Neural Network.” PloS One 15, no. 4 (2020): e0231059. https://doi.org/10.1371/journal.pone.0231059.
Verstraete, Nina, Giuseppe Jurman, Giulia Bertagnolli, Arsham Ghavasieh, Vera Pancaldi, and Manlio De Domenico. “CovMulNet19, Integrating Proteins, Diseases, Drugs, and Symptoms: A Network Medicine Approach to COVID-19.” Network and Systems Medicine 3, no. 1 (2020): 130–41. https://doi.org/10.1089/nsm.2020.0011.
PUBLICATIONS 2019
Greco, Alessandro, Jon Sanchez Valle, Vera Pancaldi, Anaïs Baudot, Emmanuel Barillot, Michele Caselle, Alfonso Valencia, Andrei Zinovyev, and Laura Cantini. “Molecular Inverse Comorbidity between Alzheimer’s Disease and Lung Cancer: New Insights from Matrix Factorization.” International Journal of Molecular Sciences 20, no. 13 (June 26, 2019). https://doi.org/10.3390/ijms20133114.
Ben Zouari, Yousra, Anne M. Molitor, Natalia Sikorska, Vera Pancaldi, and Tom Sexton. “ChiCMaxima: A Robust and Simple Pipeline for Detection and Visualization of Chromatin Looping in Capture Hi-C.” Genome Biology 20, no. 1 (May 22, 2019): 102. https://doi.org/10.1186/s13059-019-1706-3.
Forés-Martos, Jaume, Ferrán Catalá-López, Jon Sánchez-Valle, Kristina Ibáñez, Héctor Tejero, Helena Palma-Gudiel, Joan Climent, et al. “Transcriptomic Metaanalyses of Autistic Brains Reveals Shared Gene Expression and Biological Pathway Abnormalities with Cancer.” Molecular Autism 10 (2019): 17. https://doi.org/10.1186/s13229-019-0262-8.

TEAM MEMBERS

Leila Khajavi
Chercheur Post-Doctorant / Post-Doc researcher
Hugo Chenel
Ingénieur de laboratoire / laboratory engineer
Abdel Mounim Essabbar
Ingénieur de laboratoire / laboratory engineer
Benoît Aliaga
Chercheur Post-Doctorant / Post-Doc researcher
Nina Verstraete
Chercheur Post-Doctorant / Post-Doc researcher
Matthieu Genais
Doctorant / PhD student
Jacobo Solorzano
Doctorant / PhD student
Miguel Madrid-Mencía
Ingénieur de laboratoire / laboratory engineer
Alexis Coullomb
Chercheur Post-Doctorant / Post-Doc researcher
Hadi Kabalane
Chercheur Post-Doctorant / Post-Doc researcher
Julie Bordenave
Ingénieur de laboratoire / laboratory engineer
Malvina Marku
Chercheur Post-Doctorant / Post-Doc researcher
Flavien Raynal
Ingénieur de laboratoire / laboratory engineer
Vera Pancaldi
Chercheur statutaire / permanent scientist
Julien Pernet
Ingénieur de laboratoire / laboratory engineer
Alexis Hucteau
Doctorant / PhD student

 PARTNERSHIPS & funding

Centre de Recherches en Cancérologie de Toulouse

Centre de Recherches en Cancérologie de Toulouse (Oncopole)

Toulouse – FR

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05 82 74 15 75

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