Senior Lecturer in Ophthalmology with research interests in inherited eye disease and therapies 

Director of International PGR

MSc Unit Lead for ‘Disease Modelling and Genome Engineering’

MSc Unit Lead for ‘Genomics of the Eye’. 

Portfolio Tutor and PBL Tutor for MBChB Medicine programme.

I gained my PhD at the University of Aberdeen (1990) before completing post-doctoral positions at the University of Edinburgh (1989-1995). I then moved into the field of human genetics when I joined the laboratory of Professor Alan Wright (MRC Human Genetics Unit, Edinburgh) in 1995. There I was part of the team that first published RPGR as the gene mutated in X-linked retinitis pigmentosa RP3 and I went on to make a conditional knockout mouse model for Rpgr and was the first to discover the protein’s centriolar localisation. In 2002 I moved to The University of Manchester where I am now a senior lecturer in ophthalmology. I established and was Directeor of the MSc Genomic Medicine programmes until 2019 and am now the Faculty Director of International PGR. My research interests include correcting the function of mutant proteins associated with human disease using small molecules, and epigenetic modification of gene expression to correct pathogenic mutations.

My research interests are the genetics and functional genomics of ocular disease. My current interests include developing a therapy for the bestrophinopathies (retinal degenerations associated with the BEST1 gene) using small molecules and the genetics of primary open angle glaucoma.

Mutations in the BEST1 gene were first associated with macular degeneration (the central part of the retina responsible for detailed colour vision) in Best disease. The protein product of the gene is called bestrophin-1, and it forms an ion channel in the retinal pigmented epithelium (RPE), the pigmented layer of cells at the back of the retina. We described a new condition, autosomal dominant vitreoretinalchoroidopathy (ADVIRC), associated with mutations in BEST1 and showed that ADVIRC mutations cause mistakes in gene splicing, the process where the cell machinery pieces together different parts of a gene. We then discovered a third disease, autosomal recessive bestrophinopathy (ARB), which results from a lack of active bestrophin-1. 

I have used cell model systems and tissue derived from patient induced pluripotent stem cells to show that small molecules can rescue the expression, localisation and function of mutant bestrophin1.

Work is underway to test whether these small molecules are effective against other disease-associated proteins and alleviate disease in human patients. Using molecular modelling and docking my lab is developing a screen to identify more efficacious small molecules. I am also interested in using CRISPR-Cas9 genomic engineering tools to increase the expression of genes associated with retinal disease. 

Enquiries are welcome from self-funded students with an interest in any of the above areas. Information on how to apply can be found here. 

Unit lead for ‘Disease Modelling and Genome Engineering’ (MSc Genomic Medicine and MSc Biotechnology and Enterprise).

Unit lead for ‘Genomic of the Eye’ (MSc Investigative Ophthalmology and Vision Sciences).

PBL Tutor and Portfolio Tutor on MBChB Medicine course

• Ocular genetics: Professor Graeme Black
• Cell electrophysiology: Professor Richard Baines
• Small molecules: Dr Sally Freeman, Dr Jim Warwicker
• iPSC and CRISPR-Cas9: Professor Tao Wang, Dr Antony Adamson

Group members:

• Thomas Sadeh (Functional characterisation and correction of Congenital Stationary Night Blindness mutants)
• Kathleen Elverson (Molecular modelling of small molecules to correct protein function)
• Omamah Jiman (Analysis of next generation sequencing data from patients with inherited retinal dystrophies)

Past Group members:

• Dr Jingshu Liu (Functional correction of mutant using small molecules)
• Dr Carolina Uggenti (primary open angle glaucoma; bestrophinopathies and small molecules)
• Dr Steve Thomson (Modelling eye disease using iPSC)
• Dr Louise Porter (Brittle Cornea Syndrome)
• Ms Anna Siddell (Brittle Cornea Syndrome)
• Ms Emma Wade (POAG, miR-184)
• Dr Geoff Maher (TMEM114, TMEM235, autosomal dominant cataract)
• Dr Alice Davidson (BEST1, bestrophinopathies)
• Ms Caroline Ridley (BIGH3, corneal dystropies)
• Dr Alec Waite (hypertriglyceridaemia; VPS13B and Cohen syndrome)
• Dr Rosie Burgess (BEST1, bestrophinopathies)

Molecular genetics

Functional genomics

Disease modelling in model systems (mice, Xenopus, zebrafish, cells, iPSC)

Genomic editing (CRISPR-Cas9)

PhD (1990) University of Aberdeen

BSc (1985) Edinburgh Napier University