MALVINA MARKU
Multiscale dynamical modelling of the tumor microenvironment
In any multicellular system, the ecology, dynamics and stability of each cell population is determined by both the cell-cell interaction and the cell-specific molecular regulation. In a tumour setting, identifying the mechanisms that establish the immune cell – cancer cell interactions is crucial in understanding the tumour behaviour and response. We focus on the ecology of the tumour microenvironment, and particularly on the differentiation of monocytes into tumour-associated macrophages (TAMs) in Chronic Lymphocytic Leukaemia (CLL). By leveraging mathematical modeling, we dissect the dynamic properties of this biological system across various scales, from the molecular to the cellular level.
Our models provide critical insights into the influence of the tumor microenvironment on phenotypic changes. Utilizing data-driven network and model inference techniques, we aim to uncover condition-specific features within gene interactions and cellular phenotypes. These sophisticated models facilitate in silico experiments, enabling the identification of potential drug targets, thus advancing therapeutic strategies.
Selected papers
- Hugo Chenel, Malvina Marku, Tim James, Andrei Zinovyev & Vera Pancaldi. Multilayer network approaches to omics data integration in Digital Twins for cancer research Arxiv: https://doi.org/10.48550/arXiv.2410.07252
- Marku M, Pancaldi V. From time-series transcriptomics to gene regulatory networks: A review on inference methods. PLOS Computational Biology. 2023 Aug 10;19(8):e1011254.
- Verstraete, N., Marku, M., Domagala, M., Arduin, H., Bordenave, J., Fournié, J.-J., Ysebaert, L., Poupot, M., & Pancaldi, V. 2023. An Agent-Based Model of Monocyte Differentiation into Tumour-Associated Macrophages in Chronic Lymphocytic Leukemia. iScience May 19;26(6). https://doi.org/10.1016/j.isci.2023.106897
- Malvina Marku, Hugo Chenel and Vera Pancaldi. Dissecting Cellular Phenotypes in the Tumour Microenvironment through Gene Regulatory Networks: Inference, Analysis and Dynamical Modelling, in Immunology and Cancer Biology, Vide Leaf 2023
- Marku M, Verstraete N, Raynal F, Madrid-Mencia M, Domagala M, Fournié JJ, Ysebaert L, Poupot M, Pancaldi V. 2020. Insights on TAM Formation from a Boolean Model of Macrophage Polarization Based on In Vitro Studies. Cancers. Dec 12(12): 3664-3687. doi.org/10.3390/cancers12123664.
Grants:
ANR RD2Bool
https://rd2bool.github.io/
Reconciling data driven and prior knowledge approaches to infer cell-type specific ensemble Boolean models using single cell multi-omics time courses
PEPR CellID,
Labelisation Ligue Nationale Contre le Cancer
