Our lab is generally focused on modeling, understanding, and treating neurodegenerative disease by integrating concepts across engineering, neuroscience, and cellular and molecular biology. We regularly leverage simple cell culture platforms, 3D engineered systems, human tissue, and in vivo models to study biological function and deconstruct mechanisms of disease. We also seek to develop engineered platforms, techniques, and strategies that can be applied back to basic wet lab research, model development, and drug delivery. In this talk, I will first highlight work focused on developing complex models of vascularized human brain tissue. Next, I will outline some of our emerging work on nonviral gene targeting in the brain using lipid-siRNA conjugates. Across each area, I will discuss how we envision leveraging these efforts to combat Alzheimer’s disease, cerebral amyloid angiopathy, and tauopathies.