Our lab is studying the genetics of obesity, in particular, the molecular mechanisms that regulate appetite. We focus on SIM1, a hypothalamic transcription factor mutated in a girl with severe, early onset hyperphagic obesity. We identified neuroendocrine pathways regulating feeding behavior that are perturbed in a mouse Sim1 knockout model that recapitulates the girl's hyperphagic obesity phenotype. We are presently using conditional knockout mice to dissect Sim1’s temporal and spatial actions. We are also seeking to identify Sim1 transcriptional target genes in CNS neurons relevant to appetite regulation.