My research interest is the control of neuronal gene expression. The major focus of the lab is on the neuropeptide CGRP and its role in migraine. The role of CGRP in migraine is supported by the ability of CGRP to cause headache and the recent efficacy of a CGRP antagonist as an antimigraine drug. We have found that the CGRP gene is up-regulated by cytokine-induced MAP kinases and repressed by antimigraine drugs that appear to act via an unusually prolonged calcium signal. We are currently investigating these mechanisms using adenoviral-mediated gene transfer to cultured trigeminal neurons and intact ganglia in vivo. We are also using gene transfer and transgenic mice to regulate CGRP receptor activity in the vasculature and nervous system by overexpressing the RAMP1 subunit of the CGRP receptor. The RAMP1 transgenic mice are sensitized to CGRP-induced neurogenic inflammation. The RAMP1 transgenic mice display a unique phenotype has raised the possibility that these mice may provide a model for some aspects of migraine, which is currently being explored. In collaborative projects, we are studying the beneficial effects of CGRP against hypertension and following myocardial infarction in the RAMP1 mice. Other collaborative projects include the regulation of serotonin biosynthesis, which may be important in migraine and behavioral disorders, and use of the CGRP promoter to target a dominant negative oncogene to specific neuroendocrine cells. The overall goal of these projects is to develop effective diagnostic and therapeutic strategies.