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My research interests involve the regulation of neuronal gene expression. The major project in the lab involves the neuropeptide CGRP in migraine. The long-term goal is to develop effective gene therapy and diagnostic strategies for migraine and other neurovascular disorders. We have found that the CGRP gene is auto-induced and stimulated by cytokines that act via MAP kinases, which suggests the possibility of positive feedback loops in migraine. We are using viral-mediated gene transfer to regulate CGRP levels and as an imaging tool to measure promoter activity in the nervous system in vivo. In parallel studies we are selectively over-expressing the RAMP1 subunit of the CGRP receptor in mice. One objective is to generate a physiological mouse model for migraine. Initial results indicate that the RAMP1 mice have been sensitized to CGRP action in the nervous system, with increased neurogenic inflammation, mechanical allodynia, and light aversive behavior. They also have increased metabolism and greatly reduced body fat. Mice with RAMP1 overexpressed throughout the body show a remarkable protection against hypertension. These studies may shed light on neuromodulatory roles of CGRP in migraine and cardiovascular disease.
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