Our lab is interested in characterizing mechanisms regulating Alzheimer’s pathogenesis and neuronal dysfunction. We apply an integrated approach that combines molecular neuropathology analyses, biochemical characterization, detailed subcellular localization, advanced microscopy and live-cell imaging, RNAseq and spatial transcriptomics, electrophysiology, and behavioral tests to accomplish our goals. Cultured primary hippocampal neurons, microglia, oligodendrocytes, established cell lines, hiPSC lines, transgenic mice, and conditional knock-out mice serve as experimental models in our investigation.
We have a major focus on BIN1, the second most significant late-onset AD risk factor. Our goal is to characterize cell-type-specific BIN1 conditional knock-out and BIN1 transgenic mice to understand BIN1’s function in neurons and glia and determine how this GWAS AD risk factor influences Aβ and tau pathology and neurodegeneration. Recently, we published key findings on microglial BIN1 function in neuroinflammation. Our study describing BIN1 regulation of region-specific tau pathogenesis and neurodegeneration in the PS19 model highlights BIN1’s role in promoting hippocampal tau pathophysiology.