My overall research interest is to understand brain regulatory mechanisms that influence neuroinflammatory response in the context of aging, obesity, and cognitive function. My ongoing research has shown that the brain hormone orexin A (OXA) is neuroprotective and decreases hypothalamic inflammation by 1) altering neuronal metabolism, and 2) by preventing the activation of neurotoxic microglia (brain immune cells). The underlying mechanisms that dysregulate microglia, ultimately leading to neurodegeneration, are not fully understood. The linkage of inflammation and lipid metabolism also point towards an unexplored role for the fatty acid binding protein-uncoupling protein-2 (FABP-UCP2) axis in mechanism of lipid-mediated exacerbation of cognitive impairment.
Orexins were first identified in 1998. Despite the advances in understanding the organization of the orexin system since this time, there are large gaps in the knowledge of how OXA effects changes in target neurons via the activation of its two known G-protein coupled receptors (GPCRs), orexin receptors 1 (OX1R) and 2 (OX2R). I am particularly interested in determining the second messenger systems of these receptors and the resulting downstream activation of particular gene products and proteins. The identification of unique OXA-induced intracellular signaling cascades within specific target brain regions would provide novel avenues for therapeutic treatment of neuroinflammation and neurodegeneration.
Cayla Duffy is a graduate student in the Butterick Lab. Cayla is currently pursuing her PhD in the UMN Department of Food Science and Nutrition. Cayla's research is currently focused on the role of microglia in neuroinflammation. Her work has resulted in several first-authored manuscripts and has led to productive collaborations with other researchers at UMN and the Minneapolis VAHCS.