Lisa Cirillo

Work in my lab focuses upon FoxO and FoxA pioneer factors, transcription factors with essential roles in liver development and in hepatic glucose, lipid, cholesterol, and bile acid metabolism. My laboratory has demonstrated that interdependent chromatin binding and remodeling by FoxO1 and FoxA is essential to maintain an active chromatin environment as well as to establish a substrate for the binding of additional accessory factors required for transcription of insulin-regulated genes in the liver. Taken together with ChIP-Seq data showing that FoxO1 and FoxA co-target multiple insulin-regulated genes in the glucose, carboxylic acid, lipid, and steroid metabolic pathways, our findings point to interdependent FoxO1/FoxA binding as a general regulatory mechanism that is required to establish and maintain active chromatin states in response to extracellular cues that regulate a broad array of hepatic metabolic processes tied to insulin signaling through PI3K/Akt. Current research efforts are focused on 1) confirming coordinate regulation of FoxO1/FoxA co-targeted genes in hepatocytes, 2) identifying accessory proteins co-recruited by FoxO1/FoxA to these genes, and 3) investigating how these co-recruited proteins cooperate with FoxO1 and FoxA to poise insulin-regulated genes for activation and hormonal regulation. Subversion of the corresponding gene regulatory events is a likely contributor to multiple metabolic derangements, including diabetes, making it vital that we uncover the key mechanisms and players.