Rosa Bartolomeo

Genetic vaccines targeting tumor neoantigens delivered through viral vectors

Title and summary of PhD project Exploiting the cross talk between lysosome and signalling to treat lysosomal storage disorders Lysosomal storage disorders (LSDs) are inherited diseases characterized by progressive intracellular accumulation of undigested macromolecules due to lysosomal dysfunction. This results in a complex phenotype with broad pathological manifestations. Most LSDs are characterized by defective skeletogenesis. Despite this, the mechanisms by which lysosomal storage affects skeletal development and function is still unknown and the efficacy of current therapies on the skeletal system is limited. This project aims at identifying the molecular mechanisms that underlye the skeletal abnormalities in LSDs and to develop novel therapeutic strategies directed toward these defects. In recent years, the lysosome has emerged as a key signaling centre, which regulates and is in turn regulated by the activity of signaling molecules. By using the Mucopolysaccharidosis VII (MPSVII) mouse as a model of LSD, we plan to characterize the consequences of lysosomal dysfunction on major signaling pathways involved in skeletogenesis, and to identify tools and pathways that prevent accumulation of storage in bone cells both in vitro and in vivo. Supervisor: Carmine Settembre, PhD Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy

The research project focused on gene therapy for inherited eye diseases due to mutations in large genes. Supervisor: Alberto Auricchio, M.D.