Description of Research Expertise

My laboratory studies the paraventricular nucleus of the hypothalamus (PVH), and the hypothalamic regulation of feeding, energy expenditure and body weight. We are currently using various mouse lines, to examine the importance of each PVH neuron subtype in feeding, energy expenditure, and body weight regulation. We use various methods including surgical and pharmacological methods as well as in-vivo neuron-specific ablation, activation and inhibition.

PVH neurons in energy homeostasis regulation: The paraventricular nucleus of the hypothalamus (PVH) functions to integrate peripheral adiposity signals such as leptin and is important in meal termination. Its ablation results in hyperphagic obesity. The PVH harbors the cell bodies of second order neurons that receive projections from leptin responsive Pomc and Npy/Agrp neurons in the arcuate. PVH Oxytocin (OXT), corticotropin releasing hormone/factor CRH/CRF and thyrotropin releasing hormone (TRH) neurons are leptin and melanocortin responsive and project to brain regions regulating satiation and energy expenditure. We aim define the role of each of the above neuron subtypes in the PVH to examine the effect on feeding regulation, energy expenditure and body weight.

Mechanism of hyperphagia in Prader-Willi Syndrome (PWS): PWS is a genetic disorder that causes neonatal feeding difficulties and failure to thrive followed by a switch to severe hyperphagia in childhood. The pathogenesis of every aspect of feeding regulation in PWS is unknown. In fact, basic elements of our understanding of the hypothalamic regulation of feeding are missing. PWS is caused by loss of several paternally inherited genes on a small locus on chromosome 15. The mouse PWS locus contains the same genes in the same order as the human locus. Like humans, mouse models of PWS also display neonatal failure to thrive with the larger deletions leading to earlier neonatal lethality. Unlike humans, PWS mice do not develop hyperphagic obesity. Many of the genes in the PWS locus are expressed in the hypothalamus and PWS is characterized by hypothalamic dysfunction. Importantly, patients with PWS have a reduced number of oxytocin neurons in the PVH of the hypothalamus as well as low circulating levels of oxytocin. We aim to define the role of the PVH and oxytocin in feeding regulation in PWS.