UCL Institute of Ophthalmology

Prof Jacqui van der Spuy

Prof Jacqui van der Spuy

Professor of Molecular and Cellular Biology

Institute of Ophthalmology

Faculty of Brain Sciences

Joined UCL
1st Oct 2000

Research summary

My research is focussed on the molecular neurobiology of inherited retinal dystrophies and neurodegenerative diseases, and the translation of fundamental molecular and biochemical insights of disease-causing mechanisms to therapeutic interventions. Investigations of neurodegeneration in inherited retinal diseases have focussed on advances in understanding the fundamental molecular mechanisms of neuropathology in Leber’s congenital amaurosis type 4 (LCA4), one of the most severe and early onset forms of inherited retinal degeneration, both validating disease-causing LCA4-associated mutations and their consequent impact on the assembly of a heterocomplex required for functional phototransduction, as well as identifying aberrant pre-mRNA missplicing as a causative underlying mechanism of LCA4. This research has strongly impacted the therapeutic strategy for patients, assisting the triage of patients for gene therapy, and the exploration of fundamental disease mechanisms and targeted therapies has been extended to other inherited retinal dystrophies, including non-syndromic and syndromic early onset inherited retinal diseases and juvenile macular dystrophies. My research aims to develop new pre-clinical models of these human retinal dystrophies using three dimensional retinal organoid and retinal pigment epithelium models, with the aim of combining advances in fundamental insights in molecular and cellular neuroscience with advances in stem cell and gene editing technologies to model retinal degeneration and explore new therapeutic approaches. This includes the validation and optimisation of pharmacological and gene therapy approaches, and the exploration of antisense oligonucleotide therapies and direct base and prime editing approaches for inherited retinal diseases intractable to classical gene therapy approaches.