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.
