Research Abstract:
Research in our laboratory aims to identify and characterize molecular genetic determinants of cataracts; a leading cause of visual impairment. Two complementary approaches are ongoing. (1) Mapping and mutation studies: Genome-wide markers are being used to map and refine novel chromosomal loci for inherited cataracts. Targeted re-sequencing techniques are also being used to (a) identify causative mutations in positional-candidate genes linked with inherited cataracts, (b) develop diagnostic genetic tests for inherited cataracts, and (c) identify susceptibility variants in candidate genes associated with age-related cataracts. (2) Pathogenetic studies: Mice harboring spontaneous or targeted mutations in the genes for (a) a water-channel, (b) a cell-junction protein, (c) a chromatin-modifying protein, and (d) a tyrosine-kinase receptor are being used as model systems to elucidate the pathologic mechanisms underlying the development of cataracts and associated eye disorders in humans. |
Selected Publications:
Shiels A, Bennett TM, Knopf HLS, et al. The EPHA2 gene is associated with cataracts linked to chromosome 1p. Mol Vis 2008 14:2042-2055.
Shiels A, Bennett TM, Knopf HLS, et al. CHMP4B, a novel gene for autosomal dominant cataracts linked to chromosome 20q. Am J Hum Genet 2007 81:596-606.
Shiels A, Hejtmancik JF. Genetic origins of cataract. Arch Ophthalmol 2007 125:165-173.
Shiels A, Bassnett S, Varadaraj K, et al. Optical dysfunction of the crystalline lens in aquaporin-0-deficient mice. Physiol Genom 2001 7:179-186.
Shiels A, Mackay D, Bassnett S, et al. Disruption of lens fiber cell architecture in mice expressing an AQP0-LTR fusion protein. FASEB J 2000 14:2207-2212. |