We are broadly interested in studying and modeling the genetic networks underlying vision development and diseases. Taking a system biology approach, both experimental and computational approaches are used in parallel to identify and model gene functions during retinal development in both human and model organisms.

Currently, we focusing on identify novel genes involved in Leber congenital amaurosis (LCA) , the most common hereditary cause of visual impairment in infants and children. LCA is a set of inherited, early onset retinopathies that affect about 1 in 15,000 in the general U.S. population and account for more than 5% of all retinal dystrophies. Unfortunately, to date, no medical or surgical intervention has been shown to alter the natural course of LCA, nor has any pharmacologic therapy shown effect on modulating or moderating its progression. Currently, mutations in at least thirteen genes have been associated with recessive LCA, which account for about 63% of all cases. To clone additional LCA disease genes, in collaboration with Dr. James Lupski and Dr. Richard Lewis, we have collected DNA samples from 38 consanguineous Saudi Arabian and 80 North American families with recessive LCA. Currently, direct sequencing as well as whole genome linkage scan using the 300K SNP array platform is in progress for these families. So far, two novel disease loci have been identified and mutation identification using a candidate gene approach of these two loci is ongoing. To find more, please follow the link.

Model organisms including mouse and Drosophila melanogaster are useful tools to understand molecular mechanism of diseases and also identify genetic networks that control retinal development. In Drosophila, a major effort in our laboratory is to understand the molecular mechanism of the early retinal cell fate determination process. Retinal cell fate determination is the early phase during fly eye development and only a handful genes (RD genes) are known to control this process. To better understand the underlying genetic network, microarray, ChIP-Seq, and proteomic experiments are conducted to identify novel genes and genetic networks that function among or immediately downstream of the RD gene group. A combinatorial approach of comparative genomics, computational biology and genetic epistasis analysis is used to further identify key components that control retinal cell fate specification, determination, and differentiation. To find out more, follow the link.

Finally, developing novel applications that take advantage of the new sequencing technologies, such as Solexa and 454, is another focus of our lab. The unparallel high throughput provided by these next generation sequencing tools provide unique opportunities for better understanding many fundamental questions in molecular biology and genetics. Various experiments that takes full advantage of this cutting edge technology are underway.