Professor Orlando’s main interest is the investigation of the epigenetic mechanisms governing the dialogue between genome and environment and how those impact and evolve over a lifetime. In particular, his group studies the plastic properties of the genome in response to developmental and environmental cues and the conditions for maintenance of optimal healthy and resilient states. In this context, the lab focuses on the exploration of the emerging role of the repetitive part of the mammalian genome (50% of total). This is made of various classes of DNA sequences repeated tens of thousands of times, relics of ancient viruses that have colonized the mammalian genome and contributed to its evolution. However, recent progress has revealed a pivotal role of the RNAs coming from this portion of the genome in both epigenome dynamics and regulated inflammatory response. This evidence places repetitive and retrotransposons RNA at the center of two fundamental aspects of cell and organism physiology, aspects that when compromised are well-recognized hallmarks of unhealthy states and aging, involving loss of nuclear architecture and chronic inflammation. Therefore, understanding the regulation and targeted pathways that regulate these classes of RNAs is proving to be instrumental for devising highly innovative approaches impacting aging, tissue regeneration, and amelioration of related pathological contexts.