Drug abuse; Behavioral pharmacology; Signal Transduction; Neuropharmacology; Circadian Rhythm/Chronobiology
My lab‘s research seeks to understand the mechanism of action of the hormone melatonin at the MT1 and MT2 G-protein coupled receptors. We study these receptors in the brain and through the body with the goal of identifying ligands that exhibit useful binding affinity and therapeutic potential. Our team of undergraduate and graduate students, postdoctoral fellows, technicians and senior scientists work with each other and with expert co-investigators in medicinal chemistry to discover and develop novel molecules that can mimic or counteract the actions of melatonin. These molecules may help treat a variety of diseases and conditions including insomnia, circadian sleep disorders, depression, seasonal affective disorders, and cardiovascular disease. Our laboratory pursues these investigations from several angles. We assess the localization of the melatonin receptors, examine their cellular and molecular signaling mechanisms,and investigate receptor fate following prolonged exposure to melatonin. We study the distinct roles of selective MT1 and MT2 melatonin receptor ligands in modulating circadian rhythms, methamphetamine‘s ability to induce both sensitization to prolonged exposure, and stimulation of the reward system. We also study cell proliferation, survival, and neurogenesis in the brain, and the changes in gene expression underlying all these processes. Our research ultimately aims to discover novel drugs with differential actions at the MT1 and MT2 receptors. We use molecular-based drug design, computer modeling and medicinal chemistry to design and synthesize small molecules that target these receptors as agonists, inverse agonists and/or antagonists. We then pharmacologically and functionally characterize these molecules using cell-based assays and bioassays and test them in circadian and behavioral animal models.