Proietti lab

We are dedicated to understanding why some immune systems struggle to control inflammation or combat infections. By combining experimental and computational approaches, we aim to uncover the underlying mechanisms of immune dysregulation and advance fundamental knowledge in immunology.

Here, we focus on genetic and genomic data analysis and the development of custom software tools, databases, and applications for research data management and analysis following the FAIR principles. We can perform a wide range of bioinformatics tasks, from raw data processing to advanced analysis and visualization. Our work aims to improve the genetic diagnosis in patients with suspected inborn errors of immunity.

Here, we investigate how genetic factors determining sensing of nucleotides or nucleic acids regulate the human immune response. We have recently discovered a new and unexplored pathway related to nucleic acid sensing and immune response. We have found that ADA2 is a lysosomal protein that binds DNA and efficiently deaminates deoxyadenosine (dA) residues of DNA to deoxyinosine (dI), suggesting that DNA is its natural substrate. We also found that dA-to-dI editing of DNA and ADA2 facilitates immune detection of DNA mediated by Toll-like receptor 9 (TLR9). By elucidating ADA2’s role in DNA sensing and metabolism, our work expands our understanding of innate immunity and sheds light on potential therapeutic targets for autoimmune and autoinflammatory diseases.