Ricerc@Sapienza

Basic and translational research on lung biology and pathology can greatly benefit from the development of 3D in vitro models with physiological relevance. Lung organoids and lungs-on-chip allow the creation of different kinds of in vitro

The pressure towards innovation and creation of new model systems in regenerative medicine and cancer research has fostered the development of novel potential therapeutic applications. Kidney injuries provoke a high request of organ transplants making it the most demanding system in the field of regenerative medicine. Furthermore, renal cancer frequently threaten patients’ life and aggressive forms still remain difficult to treat.

Recent progress in the field of in vitro toxicology has led to the development of increasingly complex models that are closer to the complexity of organs and tissues, both in terms of structure and functionality, and are characterized by more precise, specif- ic and early endpoints (Ranga et al., 2014; Xinaris et al., 2015; Clevers, 2016; Jackson and Lu, 2016; Bartfeld and Clevers, 2017; Pamies et al., 2018; Truskey, 2018). The transition from traditional 2D models to three-dimensional (3D) systems cer- tainly represents the most important innovation of the last de- cades.

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Medulloblastoma (MB) is the most common malignant brain tumor in children and among the subtypes, Group 3 MB has the worst outcome. Here, we perform an in vivo, patient-specific screen leading to the identification of Otx2 and c-MYC as strong Group 3 MB inducers. We validated our findings in human cerebellar organoids where Otx2/c-MYC give rise to MB-like organoids harboring a DNA methylation signature that clusters with human Group 3 tumors.