New therapeutic targets are needed for neurodegenerative disease including Alzheimer’s and related dementias. The immune system includes many of the most successful therapeutic targets in medicine. My lab seeks to uncover mechanism by which glia and immune factors influence disease pathology in dementia to inform novel therapeutic strategies. We integrate single cell and tissue transcriptomics, epigenetic profiling, and human genetics to identify cell-specific and multicellular neuroimmune signaling networks in human dementias by applying systems biology and functional genomics. We use transgenic mouse models and human iPSC-derived 3D neuronal-glial cultures to test the roles and mechanisms of these signaling networks. This includes building and utilizing robust gene co-expression modules as conserved molecular disease phenotypes from which to study the effects of genetic and chemical perturbations. A major focus of our current work is the interplay of glial immune signaling, chromatin instability, and neuronal dysfunction in dementia, including the role of interferon-mediated immune suppression in disease pathology.