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My research involves understanding the regulation of visual signaling pathways in the vertebrate retina using mice and zebrafish as model organisms. In the past 20 years we have discovered what was a novel G protein-coupled receptor kinase, GRK7, and determined that it is found specifically in cones of the vertebrate retina where is phosphorylates cone opsins in the light. Interestingly, mice and rats have lost the gene for GRK7 and instead use GRK1 (rhodopsin kinase) in cones for this purpose. Vertebrates vary in their cone GRK profiles. For example, humans and zebrafish express both GRK1 and GRK7 in cones, whereas pigs and dogs only express GRK7. We have also determined that GRK1 and GRK7 are phosphorylated in the dark when cAMP levels are high in photoreceptors. In mouse rods, this leads to a delay in dark adaptation, whereas in cones GRK1 is not phosphorylated, so there is no effect. We are presently working with zebrafish to resolve the complexity of the regulation these GRKs by phosphorylation in rods and cones and how that might influence visual signaling.

A second project in the laboratory involves understanding early events in retinal degeneration caused by the disease, retinitis pigmentosa. There are approximately 3,000 mutations in 800 rod genes that can cause degeneration to varying levels and with different time courses. Using a mouse model with a point mutation, we are investigating the metabolomic and proteomic profiles early in the disease process to determine what factors may influence the rate of degeneration and what therapeutic options might be suggested by our studies.


UNC AFFILIATIONS:

Cell Biology & Physiology, Genetics, Neuroscience Center

CLINICAL/RESEARCH INTERESTS:

Biochemistry, Cell Biology, Cell Signaling, Metabolism, Neurobiology, Physiology, Systems Biology