The Goal: We study the etiology of metabolic disorders and diabetes, and aim to elucidate the molecular mechanisms underlying pancreatic beta cell failure and insulin resistance. Our interdisciplinary approaches span physiology, molecular biology, biochemistry, bioinformatics, and functional genomics. We utilize integrative functional genomics with next generation sequencing (ChIP-seq, RNA-seq, HiC) to obtain multi-modal, high-resolution datasets to compare and contrast human and mouse epigenetics in the context of beta cell function.

Investigating the genetic component of metabolic disorders: We discovered a novel human diabetes susceptibility gene – C2CD4A – and are actively investigating its pathophysiological relevance. We have generated several animal models, cell lines, and necessary reagents to investigate a link between pancreatic beta-cell, exercise-induced hypoglycemia, and type 2 diabetes therapy. These studies will advance our understanding of C2CD4A, and provide a blueprint for leveraging human genetics data to glean biological insights that will eventually benefit patients.

Exploring therapeutics to simultaneously promote insulin secretion and insulin sensitivity: Defects in insulin secretion and insulin sensitivity create a pathway to type 2 diabetes. With the above approaches, we found a gene called Gc, and its inhibition leads to systemic benefits, including improved insulin secretion and sensitivity, as well as reduced body weight. We are investigating the mechanism that could potentially unlock the secret of being a healthy couch potato.