Brian Polster, PhD
My lab studies basic subcellular mechanisms that govern neuroinflammation and cell death in neurodegenerative disorders, with a focus on mitochondria, the primary energy-generating organelles of the cell. Past investigations have centered on two key pathways of injury, caspase-dependent apoptotic cell death regulated by Bcl-2 family proteins and caspase-independent cell death mediated by calcium overload and mitochondrial dysfunction.
Current projects focus on the role of mitochondrial structural and functional remodeling in inflammatory microglial activation, how microglial activation exacerbates neuronal injury through nitric oxide production, and how oxygen availability influences the mechanisms of injury. The lab has pioneered the development of novel applications of Seahorse Extracellular Flux Technology, such as real-time assessment of mitochondrial respiration within permeabilized primary neurons and from whole brain tissue slices, expanding the ways in which mitochondrial function can be studied in cells of the central nervous system. The lab is also one of the few in the world conducting real-time bioenergetic measurements and live cell imaging experiments at brain physiological oxygen (15-40 mm Hg, 2-5% oxygen). The ultimate goal is to establish mitochondrial bioenergetics as a druggable target by taking rational, mechanism-based approaches to neuroprotective therapy.