University of Virginia Health System

I joined the Scrable lab in 2000. Currently, most of my work involves our line of p44 transgenic mice. These mice express a truncated version of the p53 oncogene, known as p44, and exhibit serious growth deficits, a shortened lifespan, and other symptoms associated with premature aging. I hope to help elucidate the molecular mechanisms underlying these deficits through analysis of the IGF-1/Akt signaling pathway. The IGF pathway is a major growth pathway and the only pathway that operates during embryogenesis that is associated with growth alone. Western blots done on tissue samples of p44 homozygous and non-transgenic mice show differing basal levels of expression of many key molecules in the Akt pathway. Further, embryonic fibroblasts derived from mice homozygous for the p44 transgene also show clear differences in their response to treatment with IGF as compared to those derived from non-transgenic mice. We believe the over-expression of p44 transgene is disrupting the function of normal p53 in the IGF pathway, resulting in growth deficits and the premature aging phenotype. Through this analysis we hope to learn more about the complex role of p53 in growth, development, and aging.

Another project I am working on involves the construction of a regulatable version of the human beta-actin promoter, which will be used to drive expression of a reporter gene in the mouse. With this tool in hand, we will be able to test the efficacy of various lac repressors, the temporal kinetics of de-repression by IPTG, and further characterize the lac operator-repressor system in a relatively straightforward manner. 

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