Research Statement
My laboratory explores genes expressed in mammalian retinal pigment epithelium (RPE) and photoreceptors, particularly genes involved in phototransduction, disk morphogenesis, and the retinoid cycle. We are interested in gene defects that cause blindness, and strive to understand mechanisms that lead to retina degenerations. The most prevalent diseases in humans caused by RPE and photoreceptor gene defects are retinitis pigmentosa, Leber congenital amaurosis, and macular degeneration, each consisting of many subtypes.
To study the consequence of gene mutations, we produce transgenic animal models that mimic an autosomal dominant dystrophy, or we delete a gene to generate a recessive disease model. Phototransduction genes presently under investigation are PDE6D (encoding a prenyl binding protein involved in transport and targeting), guanylate cyclases 1 and 2 (synthesizing cyclic GMP, the internal transmitter of phototransduction), and Ca2+ -binding proteins termed GCAPs. An example is autosomal dominant cone dystrophy based on mutations in the GCAP1 gene. Cone photoreceptors (see figure) are responsible for color vision and visual acuity.
The purpose of the retinoid cycle is to recycle retinal, the chromophore of the light receptor rhodopsin. Key retinoid cycle genes under investigation are retinol dehydrogenases (RDH8 and RDH12) which reduce retinal to retinol (vitamin A).
Languages
- English, fluent.