My research investigates how dysregulated lipid metabolism in microglia contributes to the development and progression of Alzheimer’s disease. Using bottom-up in vitro systems composed of hPSC-derived microglia, neurons, and astrocytes, including 3D “plaque-on-a-dish” models that enable high-resolution live imaging, I aim to define the mechanistic origins of microglial lipid-droplet accumulation and its downstream effects on lysosomal flux, inflammatory regulation, and metabolic reprogramming that disrupt microglial clearance and neuroimmune responses. Lipid-droplet-accumulating microglia represent a dysfunctional state characterized by impaired clearance and heightened inflammatory activity, and this phenotype emerges with aging and across multiple neurodegenerative contexts. By combining targeted genetic perturbations of lipid pathways with multi-omics and dynamic functional assays, I seek to map the causal links between lipid dysregulation and microglial dysfunction and to identify pathways that can be targeted to restore homeostatic and protective microglial states in Alzheimer’s disease and related dementias.