Cristian Ripoli, 2025
AHA MCA Project Title
“Enhancing synaptic therapies for neurodegenerative diseases with protein engineering”, 2025
Who he is
Cristian Ripoli is a Full Professor of Physiology at the Department of Neuroscience of the Università Cattolica del Sacro Cuore in Rome and President of the International Medicine and Surgery Degree Programme in South Tyrol. After completing his PhD in Biophysics in 2011, he gained extensive international research experience at the RIKEN Brain Science Institute and Kyoto University in Japan. He is a member of the Global Young Academy.
What he does
His research focuses on how synaptic plasticity influences neuronal signaling and aims to elucidate the cellular and molecular mechanisms underlying learning and memory in the mammalian brain. At the core of his work is the development of GEEPs (Genetically Encoded Engineered Proteins), synthetic proteins designed to repair synaptic dysfunction in experimental models of neurodegenerative diseases. His laboratory adopts a multidisciplinary experimental approach that integrates patch-clamp electrophysiology, live imaging with multiphoton microscopy, plasmid cloning, genetic material transfer via chemical and physical approaches (such as Gene Gun in organotypic slices), optogenetics, chemogenetics, two-photon glutamate uncaging and behavioral experiments. To validate the therapeutic potential of GEEPs, the group also employs a translational approach using human neurons derived from somatic cells obtained through skin biopsies from patients with neurological diseases. In parallel, his research explores strategies to optimize brain expression of engineered proteins through next-generation adeno-associated viral vectors (AAVs) and mRNA-based delivery platforms.
News from the Lab
- His group has developed a self-regulating therapeutic platform based on engineered proteins that activate only when needed. The system operates entirely on demand: the therapeutic response is triggered exclusively in affected cells because GEEPs are designed to respond to intracellular “sentinel” enzymes that signal early signs of neuronal or synaptic distress;
- The lab is expanding the technological capabilities of its multiphoton imaging system, enabling simultaneous visualization and photostimulation of synapses, significantly enhancing in vivo and ex vivo functional interrogation;
- The team is further advancing toward validating its patented technology (PCT/IB2021/056788), which is based on an engineered TEV protein for the spatiotemporal control of molecules in living cells.
