Leptin is an adipocyte-derived hormone that regulates appetite, metabolism and endocrine function primarily by binding a specific "long" receptor isoform (LRb) in the hypothalamus. Mutations in leptin or LRb in rodents and humans result in profound obesity, endocrine failure and diabetes. Our lab is taking a broad-based approach to understanding the function of LRb, first by studying the basic mechanisms that govern receptor action at the cellular level and then by tying these mechanisms to cellular and mammalian physiology. LRb transmits signals by activating the Jak2 tyrosine kinase and recruiting SH2 domain-containing signaling proteins to the phosphorylated LRb/Jak2 complex. Currently, our lab has two related areas of focus regarding the signaling and cell biology of LRb: (1) LRb signal transmission and (2) the neural substrate for leptin action.