We are interested in the loss of metabolic flexibility and other maladaptive changes in skeletal muscle which are associated with the progression of obesity to full blown type 2 diabetes. Our investigations make use of DNA microarrays, proteomic and metabolic profiling techniques to interrogate skeletal muscle and extensive post hoc bioinformatics analysis to meaningfully interpret and validate these data sets. When available, we utilize clinical muscle samples obtained from ongoing exercise, weight loss and pharmacological intervention studies. We also employ a well characterized cell culture model of obesity in which defects in fatty acid oxidation and altered lipid partitioning (which closely parallels insulin resistance) are preserved in primary cultured muscle cells from obese individuals. The long term goal of this study is to identify the biological mechanism by which these acquired or innate defects in metabolism are governed. In the not so distant future we would like to expand our investigative skills set to include gene knock out animal models, and the use of microarays to functionally correlate variations in the human genome (SNPs and CNVs) with well-defined diagnostic indicators of human fitness and health.

Changes in ubiquitin proteasome pathway gene expression in skeletal muscle with exercise and statins.Urso ML, Clarkson PM, Hittel D, Hoffman EP, Thompson PD.Arterioscler Thromb Vasc Biol. 2005 Dec;25(12):2560-6. The translation state of differentially expressed mRNAs in the hibernating 13-lined ground squirrel (Spermophilus tridecemlineatus).Hittel D, Storey KB.Arch Biochem Biophys. 2002 May 15;401(2):244-54. Differential expression of adipose- and heart-type fatty acid binding proteins in hibernating ground squirrels.Hittel D, Storey KB.Biochim Biophys Acta. 2001 Dec 30;1522(3):238-43.