tools SPANNING molecular to behavioral analyses
MICROSCOPY
We use confocal microscopy on immunostained brain tissue to gain powerful insights into changes in cellular morphology, plasticity, and pathology associated with neurodegeneration. Sophisticated dendritic spine analyses in dye-filled neurons in brain slices give us unprecedented detail into synaptic changes mediated by genetic perturbations that we make in our various mouse models. Many of these analyses follow stereotaxic brain targeting of specific genes in a cell type-specific fashion using CRISPR editing or conventional viral-mediated gene transfer in mice.
Microdialysis & Behavioral analyses
Understanding in vivo physiology gives us the opportunity to link changes in synaptic function to organismal behavior. For this reason, we are chiefly interested in examining how our systemic or CNS interventions alter brain function and real-time protein dynamics. The clues gained from this work give us the strongest insights in guiding our downstream mechanistic focus. We rely on a suite of in vivo assays, including learning and memory and motor assays, to evaluate function of the hippocampus and other brain regions. To examine in vivo protein dynamics, we utilize in vivo microdialysis to sample proteins in brain extracellular space in real-time over hours to days. Parabiosis and plasma transfer studies give us the opportunity to examine the influence of systemic factors on CNS function.
PROTEOMICS AND TRANScRIPTOMICS
We are interested in large scale interplay of networks of proteins in the blood and how this changes networks in the brain. We leverage proteomics and next-generation gene expression technology (RNAseq, TRAPseq, etc) to gain comprehensive insights into the influence of the systemic environment on the brain in varying disease contexts.