The University of British Columbia

 

 

Previous Appointments

2005-2009		Senior Lecturer Imperial College London, London UK.
1997-2004		Lecturer Imperial College London, London UK.
1992-1996		Wellcome Trust Research Fellow, Institute of Ophthalmology University College London, London, UK.
1989-1991		Visiting Post-doctoral Fellow Jules Stein Eye Institute, UCLA, Los Angeles, USA.

RESEARCH INTERESTS

Tissue fusion during development

Tissue fusion is a recurring event in mammalian embryology, playing a fundamental role for instance in the development of the neural tube, palate and the optic fissure. Most epithelial fusion events involve alignment of two sheets of tissue, such that they can be zippered together to generate a continuous layer. Molecular players are being identified for each step during tissue fusion providing a framework for understanding the regulation of this process at the molecular level. Furthermore, genetic studies have shown that gene defects causing failure of fusion in one location is often associated with failure of fusion in multiple tissues, thereby implying a subset of common mediators of fusion. We are studying optic fissure closure as a model system for epithelial fusion. Fusion defects lead to ocular coloboma which can damage the uveal tract, retina or optic nerve.

Mutation of PAX2 in humans and zebrafish eye cause ocular coloboma due to failure of optic fissure closure. Expression of Rip1 demonstrates activation of the necroptosis cell death pathway in the mutant zebrafish eye which is inhibited by a small drug molecule Necrostatin-1 (nec-1).   Nec-1 inhibits necroptosis and allows closure of the optic fissure ( Viringipurampeer IA et al, 2012. Hum Mol Genet . 21:2357-2369 ).

 

Aniridia

Aniridia is a pan-ocular condition characterized by an under-development of the iris tissue (hypoplasia) associated with cataract, Peters' anomaly, corneal disease and foveal hypoplasia. The majority of cases are caused by heterozygous genetic abnormalities affecting the PAX6 gene. We are interested in determining the precise signaling pathways that regulate normal iris development and why it goes wrong in aniridia. The critical questions to be addressed are: (i) what are the genes downstream of PAX6 that are crucial to iris development; (ii) what genes control normal foveal development.

The normal foveal depression and thickening of the outer nuclear layer (ONL) in the adult eye is absent in most cases of aniridia (A). The foveal depression is present at birth however, migration of cones to the foveal region is not complete until the 4-5 year of age (B). The absence of a developed foveal region of the retina results in poor visual acuity and colour vision deficits in patients with aniridia ( Gregory-Evans K et al, 2011. Can J Ophthalmol . 46:337-344 ).

KEY PUBLICATIONS

EXTERNAL RESEARCH FUNDING 1998-2011

Canadian Institute of Health Research
Sharon Stewart Aniridia Trust
The Wellcome Trust
Birth Defects Foundation
Medical Research Council (UK)
Fight for Sight (UK)
Funding for Science and Technology (Portugal)
British Retinitis Pigmentosa Society (UK)
St. Mary's Paddington Charitable Trust (UK)