Basic & Translational Research Programs
Pediatric Diabetes Research Center
Dr. Maike Sander's lab investigates molecular mechanisms that underlie the formation and proper function of pancreatic insulin-producing beta cells, which are affected in diabetes. A major direction of the laboratory is to explore how dynamic changes in gene expression, transcription factor occupancy, and chromatin affect beta cell differentiation and maintenance of a functional beta cell state. To unravel these mechanisms, they combine next generation sequencing-based assays with molecular, cell-based, and genetic approaches in both mice and human pluripotent stem cells (hPSCs). The laboratory has uncovered fundamental mechanisms of cell fate determination and plasticity in the context of normal beta cell development, regeneration, and pathogenesis of diabetes.Read more
Common Metabolic Diseases Genome Atlas
Dr. Kyle Gaulton's lab studies human genetic variation that affects the epigenome and gene regulation and the role of these variants in type 1 and type 2 diabetes as well as other complex diseases. Recently they pioneered the development of analytical approaches for single cell accessible chromatin and integration with genetic variation, which they have applied to pancreas, lung and mononuclear blood among other human tissues and uncovered cell type-specific mechanisms of complex disease risk. Dr. Gaulton's lab also develops collaborative platforms for epigenomic data related to complex metabolic and respiratory disease (www.diabetesepigenome.org, www.lungepigenome.org)."Read more
Maternal Metabolism and the Development of Diabetes and Obesity
Dr. Jianhua Shao's lab investigates the role of adipokines such as adiponectin in maternal and fetal metabolism. Using adiponectin gene knockout and obese gestational mouse models, they demonstrated that adiponectin plays a crucial role in maternal metabolic adaptation by controlling beta-cell proliferation. They also found that, in addition to insulin resistance, obesity impairs maternal triglyceride metabolism and fetal lipid supply, but enhances fetal beta-cell development. They also use genetic mouse models to study the function of brown adipose tissue (BAT) including the role of BAT-mediated thermogenesis in the adaptation of maternal energy metabolism and perinatal glucose metabolism.Read more
Reducing Insulin Dependence
Dr. Ulupi Jhala's lab is focused on understanding signaling mechanisms that modulate the progression of beta cell inflammation, a critical turning point in the development of type 1 diabetes. They have found that the pseudokinase TRB3 plays a key role in augmenting mechanisms that lead to beta cell death,by playing a role in ER stress as well as by compromising mitochondrial quality control and integrity.Read more
Childhood Diabetes and Obesity
Dr. Jane Kim's lab investigates the pathophysiology of childhood diabetes and obesity to better understand how these disease entities differ from their adult counterparts and to identify and treat those children at risk for diabetes or diabetic complications in a more effective manner. This translational research examines the microbiome, metabolome and genome profiles of children with both type 1 and type 2 diabetes recruited from the extensive and diverse patient population at Rady Children’s Hospital. They are also exploring the use of continuous glucose monitoring devices in infants in order to understand blood glucose patterns in early neonatal life.Read more