Inherited corneal disease Lab

We aim to identify the genetic origins and molecular mechanisms underlying inherited corneal diseases to facilitate the design and development of diagnostics and therapeutics. We are particularly focused on corneal endothelial dystrophies (CEDs), a group of clinically and genetically heterogeneous disorders that are associated with loss of corneal transparency and reduced visual acuity or blindness.

Fuchs corneal endothelial dystrophy (FECD) is by far the most common CED, affecting up to 4.5% of individuals over 50 years of age. It is an age-related disease with approximately 75% of cases attributed to a non-coding triplet repeat expansion in the TCF4 gene. This makes FECD the most prevalent triplet repeat-mediated disease in humans. We are currently undertaking a range of experimental approaches to advance understanding of the genetic and cellular mechanisms of dysregulation that underlie this disease so that innovative diagnostic therapeutic strategies can be developed for this common and visually disabling disease.

Another major focus of the team is advancing our understanding of posterior polymorphous corneal dystrophy (PPCD), a rare genetically heterogenous autosomal dominant disease typically associated with abnormal proliferation and multi-layering of corneal endothelial cells that can cause secondary glaucoma and blindness. Here we are focused on identifying the full range of genetic causes responsible for disease and determining the unifying molecular features of dysregulation that give rise to the condition. Our work in this area aims to identify transcriptomic signatures of dysregulation and cellular biomarkers to facilitate the design of innovative therapeutic strategies for all genetic subtypes of the disease.

In summary, our lab strives to advance and influence future therapies and diagnostic approaches by advancing understanding of the genetic causes and molecular mechanisms underlying inherited corneal disease, in collaboration with academic, biotech and clinical leaders. Data and insights generated by our lab have far-reaching relevance to a broad range of disciplines including repeat-expansion mediated disease mechanisms, precision medicine, gene-directed therapies and functional genomics.