John Lukens, PhD, an associate professor of neuroscience, received a multi-year funded award for his $2.7 million NIH grant application to study the role of an immune receptor in Alzheimer’s disease. The initial award of $1.65 million was provided for three years, with a $1 million, two-year second phase option available.
In recent years, the C-type lectin receptor CLEC7A has emerged as a widely used marker of disease-associated microglia in Alzheimer’s disease. Yet, the actual role of CLEC7A in neurodegenerative disease pathogenesis has not been studied in great detail to date. In their preliminary studies, the Lukens Lab revealed that genetic deletion of CLEC7A in a mouse model of Alzheimer’s disease leads to greatly reduced levels of amyloid beta deposition, increased recruitment of microglia to plaques, and significantly improved neuronal health. For this project, the Lukens lab will leverage a unique combination of CLEC7A conditional knockout mouse strains, CLEC7A-deficient human induced pluripotent stem cell-derived microglia-like cells, and CLEC7A modulating agents to further uncover roles for CLEC7A in the regulation of microglia responses and Alzheimer’s-related disease progression.
The vast majority of the preliminary data provided in support of this application was generated by undergraduate student Caroline “Coco” Holliday under the mentorship of graduate student Hannah Ennerfelt in the Lukens Lab. Follow-up data generated for the resubmission was generated by graduate student Addie Walsh in the Lukens Lab. Coco Holliday recently graduated from UVA and is now pursuing a PhD in immunology at Harvard. Hannah Ennerfelt, PhD, was awarded the Peach Award, which recognizes the most outstanding graduate student in the BIMS program and is now pursuing a postdoctoral fellowship at Stanford University. Addie Walsh is a rising third-year graduate student being supported by the UVA Biotechnology Training Grant.