We use a variety of super-resolution microscopy approaches (STORM, PALM, DNA-PAINT) to investigate chromatin structure changes in somatic, cancer and stem cells (Cosma & Lakadamyali Nature Methods 2020; Nature Reviews Molecular Cell Biology 2025). In collaboration with Melike Lakadamyali, we have identified a new model of chromatin fiber assembly and its relation to pluripotency (Ricci et al., Cell 2015; Otterstorm et al., NAR 2019; Garate et al., NAR 2024). In addition, we study 3D genome folding and discovered that RNA Polymerase II–dependent supercoiling controls chromatin looping and 3D genome organization ( Nueguembor et al., Molecular Cell 2021; Castells-Garcia et al., NAR 2022; Gonzalez-Almela et al., Nature Communications 2025). Combining modeling, super resolution imaging, and genomic data, we have characterized gene structure at nucleosomelevel resolution (Nueguembor et al., Nature Structure and Molecular Biology 2022).

Recently, we leveraged super-resolution imaging data to train a CNN model and developed AINU (AI of the Nucleus), which can predict cellular state with 100% accuracy (Carnevali et al., Nature Machine Intelligence 2024).

We studied mechanisms of cell-to-cell fusion (Sottile et al. Cell Reports 2017) and ploidy maintenance (Frade et al. Science Advances 2019). Recently we discovered that human Muller Glia can fuse with different human cells and studied the differentiation of the hybrids (Bonilla-Pons et al eBioedicine 2022). In vivo, we previously showed that bone marrow (BM) cells fuse with retinal neurons and Muller glia cells in degenerated mouse retinas. The in-vivo formed hybrids undergo reprogramming and regenerate neurons in drug-induced and genetic models of retinal degeneration (Sanges et al. Cell Reports 2013; J. of Clinical Investigation 2016; Pesaresi et al. eBiomedicine 2018). Furthermore, other key discoveries showed that BM-derived hybrids can functionally rescue dopaminergic neurons in two Parkinson’s disease mouse models (Altarche-Xifro et al., eBiomedicine 2016) and regenerate mouse liver after hepatectomy (Pedone et al., Cell Reports 2017). Finally, we recently identified the released chemokines from damaged human and mouse retinas and in turn we defined the chemokine-receptor interactions to enhance the migration and integration of transplanted cells into the mouse retina (Pesaresi et al. Molecular Therapy, 2021).