We use two model systems:  

1. Gastruloids, tiny 3D structures made from stem cells that mimic early embryos. These models allow us to monitor enhancers in real time and test how they regulate genes involved in EMT.Using advanced microscopy, genome editing (CRISPR/Cas9), and single-cell sequencing, we will: (1) Examine how deleting enhancers affects the activity of genes that control EMT, including the cadherin switch (E-Cadherin to N-Cadherin); (2) Study whether enhancers work independently or cooperatively to control EMT-related genes in individual cells; and (3) Test how enhancers respond to environmental signals and to natural genetic variants, helping us understand why small DNA changes can sometimes cause disease. By using gastruloids instead of animal embryos, this study also provides an ethical model for studying enhanceropathies and may reveal why misregulation of EMT contributes to cancer.
2. Human mammary epithelial cells: a cellular model in which EMT can be triggered in a controlled manner through the activation of a key transcription factor (SNAIL1). This system allows us to study EMT in a pathological context, mimicking the processes that lead to metastasis formation in breast cancers. By combining genomic approaches (ATAC-seq, ChIP-seq, Capture Hi-C), bioinformatics, and genetic engineering, we will: (1) Map enhancers specific to epithelial and mesenchymal states and identify their target genes; (2) Decipher the transcription factors and signalling pathways (TGFβ, Hippo) that activate or deactivate these enhancers during the transition; (3) Identify novel therapeutic targets to block EMT and prevent metastatic dissemination.

This research will generate a detailed map of enhancer function during EMT, showing how cells reorganize to form developmental and pathological tissues.