University of Virginia Health System

The ability to cope with stress is an essential survival mechanism in animals. My laboratory is interested in understanding the effects of stress on energy homeostasis and the implications in the development of metabolic-endocrine disorders such as obesity and type II diabetes. Corticotropin-releasing factor (CRF) family peptides and their receptors (CRFR1 and CRFR2) are key mediators of stress response and we are focusing on their role in the central nervous system in regulating appetite and metabolism. We employ transgenic mice combined with viral gene delivery to elucidate the neurocricuits of CRF family in the brain and use conditional, neuron-specific gene targeting methods to determine the functional importance of the neurocircuits in controlling feeding and body weight. At the molecular level, we are investigating signaling mechanisms and molecular targets in neurons mediating the effects of CRF peptides. These studies will contribute to understanding the underlying mechanisms of stress on energy balance and have implications in the management of eating disorders and obesity.
 
In addition to the central nervous system, CRF family peptides are expressed in the periphery and have important biological functions in these tissues. In particular, we have shown that Urocortin 3, a CRF related peptide, is expressed in pancreatic b-cells and plays an important role in regulating insulin and glucagon secretion. Our findings suggest that CRF family peptides in the periphery may have important functions in glucose homeostasis regulation. We use a number of gene targeting approaches including BAC transgenesis, cell type specific knockouts, and in vitro islet culture to explore the functional role of Urocortin 3 in the pancreas on islet hormone secretion and b-cell glucose sensing mechanism.

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