Cell Biology and Physiology
Area of interest
My lab is one of the first laboratories to clone GRK7 and identify its function as a cone opsin kinase. My laboratory was also instrumental in defining the heterogeneity of GRK1 and GRK7 expression in vertebrates, leading to a re-evaluation of the appropriate models for human cone phototransduction. In particular, this work clarified differences in pathophysiology between retinas from Oguchi disease patients and the GRK1-/- mouse, which serves as a model for the disease. Our present efforts are directed towards understanding the roles played by GRK1 and GRK7 in cone signaling and pursuing the novel observation that GRK1 and GRK7 are phosphorylated by cAMP-dependent protein kinase (PKA) in model animals using mouse models expressing mutants of GRK1 lacking the PKA phosphorylation site. In zebrafish, we are comparing the functional consequences of knocking out GRK1 and GRK7 individually as well as studying the effect of GRK phosphorylation by PKA. We are also using broad-spectrum, untargeted metabolomics for studying the role of metabolism in neurodegenerative diseases. Using a mouse model for the retinitis pigmentosa (RP), we determined purine and pyrimidine synthesis was markedly altered in a pairwise comparison between rd10 mice (a model for RP) and wild type mice, suggesting altered mitochondrial DNA synthesis. We have established the technique of electroretinography (ERG) in our laboratory to allow us to evaluate changes in visual signaling in mice and zebrafish in a noninvasive manner. Using this technique, we are able measure sensitivity, recovery and light adaptation in these animals.
Awards and Honors
1978 Biology Department Honors, Franklin and Marshall College
1984 Predoctoral Fellowship, Oak Ridge Associated Universities.
1986-1989 National Research Service Award, National Institutes of Health.
1992-1997 Established Investigator of the American Heart Association.
2013-2014 Grant Supplement from the NIH Common Fund for metabolomics research with RTI
Fall, 2015 RTI University Scholars Award for metabolomics research