Obesity-linked insulin resistance is the most common precursor to the development of type 2 diabetes. Our previous work has shown that phosphorylation of PPARy at serine 273 stimulates a pattern of gene expression in obese adipose tissues associated with insulin resistance and type 2 diabetes. Inhibition of this modification is a major therapeutic mechanism for anti-diabetic drugs acting on PPARy, such as the thiazolidinediones (TZDs) and partial/non-agonists. Despite being powerful insulin sensitizing agents, the side effect profile of the TZDs limits their clinical utility. We would like to understand how the insulin sensitizing properties of the TZDs are linked to their ability to block PPARy phosphorylation in order to rationally target this pathway using safer new approaches.

Development of new tools for obesity research: The Banks lab also directs the Energy Balance Core to study metabolic alterations which lead to obesity in mice. This equipment includes an indirect calorimeter containing gas exchange sensors to measure rates of conversion O2 into CO2, and sensitive scales to measure food intake. The large datasets produced by indirect calorimetry previously produced a statistical bottleneck. Our group developed CalR, a free indirect calorimetry data analysis tool now used on more than 30,000 experiments. We are continuing to develop new software tools for metabolic analysis.