NARILIS lunch seminar | Damien DETRAUX & Marcelo RAMIREZ-AVILA present their work

Damien Detraux

Postdoctoral researcher at UNamur, NARILIS, URBC - Research group of Prof. Patsy Renard

Dissecting and modulating mitochondrial drivers of cardiac fibroblast-to-cardiomyocyte conversion

Cardiovascular diseases cause nearly 20 million deaths annually, with myocardial infarction leading to irreversible cardiomyocyte (CM) loss and poor regenerative capacity. Direct reprogramming of cardiac fibroblasts (CFs) into induced cardiomyocytes (iCMs) offers a promising regenerative approach by bypassing pluripotency. In this study, human iPSC-derived CFs are first activated into a myofibroblast-like state, then transdifferentiated using a doxycycline-inducible MEF2C-GATA4-TBX5 (MGT) construct for controlled gene expression. Comparative transcriptional, structural, and metabolic analyses between converted and non-converted cells, alongside hiPSC-CMs, aim to uncover barriers to efficient reprogramming. Given the crucial role of mitochondria in lineage conversion, the study emphasizes mitochondrial remodeling as a key determinant of success. Quantitative proteomics reveal profound mitochondrial changes in activated CFs, correlating with network morphology. To enhance iCM maturation and function, metabolic regulators and small molecules are tested to promote mitochondrial biogenesis, oxidative phosphorylation, and the metabolic transition from glycolysis to fatty acid oxidation, hallmarks of mature CMs. Finally, 3D spheroids combining CFs and hiPSC-CMs provide a physiologically relevant platform to model direct conversion. Altogether, this integrative strategy advances understanding of mitochondrial dynamics in reprogramming and supports the development of improved in vitro cardiac repair models.

Marcelo Ramírez-Ávila

Researcher at UNamur, naXys, Department of mathematics

Visiting researcher at ULB, Unit of Theoretical Chronobiology

A Simple Model for Radiotherapy and the Implication of Chronobiological Aspects

A simple nonlinear model based on logistic growth and Lotka-Volterra competition, which describes the interaction and, consequently, the population dynamics of cancerous, healthy, and effector cells, is presented. In addition, situations in which intermittently high doses of ionizing radiation act on the cells, as occurs during radiation therapy, are considered. Irradiation parameters such as the total dose delivered, the dose rate, and the number of treatment sessions are used to identify situations where normal cells are predominant. Eventually, it was found that the times in which radiation is applied play a crucial role in the efficiency and effectiveness of treatment, which indicates the importance of chronobiological aspects.