DrVincenzo De Paola

Dr. Vincenzo De Paola is a translational neuroscientist whose research focuses on understanding the mechanisms of synaptic and axonal dysfunction that drive cognitive decline in neurodevelopmental and neurodegenerative disorders, and on translating these discoveries into disease-modifying interventions. His work integrates human genetics, single-cell multiomics, patient-derived stem cell models, and humanised in vivo platforms to discover and validate therapeutic targets.

His laboratory has established a proprietary translational platform that combines patient-derived induced pluripotent stem cells (iPSCs), self-assembling human cortical circuits, in vivo multiphoton imaging, and xenotransplantation to study human neural development and degeneration in vivo. This platform, first described in Science, enables longitudinal functional analysis of human neuronal circuits and provides a powerful system for evaluating novel RNA-based approaches, including human-sequence antisense oligonucleotides (ASOs), without the need for surrogate mouse sequences.

Using Down syndrome as a genetically defined model of accelerated Alzheimer's disease, Dr. De Paola's group generated the largest single-cell atlas of the developing Down syndrome cortex, published in Nature Medicine (2026). These studies identified upstream chromosome 21 transcriptional regulators driving early disease pathogenesis and led to the development of patented ASOs, now being advanced through TheraSvil Bio (in formation), a biotechnology company developing first-in-class RNA therapeutics for Down syndrome, Down syndrome-associated Alzheimer's disease, and genetically defined rare disorders of cortical development.

Earlier in his career, Dr. De Paola made pioneering contributions to systems neuroscience through some of the first direct observations of synapse formation, elimination, and axonal regeneration in the living mammalian brain. His research has since evolved from fundamental studies of neural circuit biology to the development of innovative RNA-based approaches for neurological disease.

Dr. De Paola received his PhD in Molecular and Cellular Neurobiology from the Friedrich Miescher Institute (University of Basel) under the supervision of Dr. Pico Caroni and completed an EMBO Postdoctoral Fellowship at Cold Spring Harbor Laboratory with Dr. Karel Svoboda. 

He established his independent laboratory at Imperial College London, where he secured a >US$4.8 million MRC Programme Grant and directed the Neuroplasticity and Disease Group as a tenured faculty member. In 2021, he joined Duke-NUS Medical School in Singapore as Full Professor of Translational Neuroscience, where he built an internationally recognised programme spanning human neurobiology, target discovery, and RNA-based drug development. His research programme has attracted over US$11 million in competitive funding across the UK, Europe and Singapore.