Alzheimer’s disease (AD) is a devastating neurodegenerative disease affecting millions worldwide. The Hansen lab discover cholesterol regulation of amyloid production.
In the brain cholesterol is produced in astrocytes. And the movement of cholesterol from astrocytes to neurons by apoE drives amyloid production. The same cholesterol also drives hyper-excitability through ion channel modulation. These finding helped establish a role for apoE4 as the most common genetic marker of late onset AD.

Anesthetics are the main tools for reversing pain. Their molecular mechanism in particular for inhaled anesthetics, has been poorly understood. The Hansen lab found a membrane mediated mechanism based on ordered lipid domains. These lipid domains behave like ordered proteins and bind to and inhibit anesthetic sensitive potassium channels. Anesthetics compete for the binding to ordered lipids, displacing the protein and activating the potassium channel. These finding established the first molecular basis for membrane mediated anesthesia.

To sustain life, the heart constantly beats with a dynamically controlled threshold. Bad diets have produced an epidemic of heart disease. Potassium channels, including inward rectifier 2 (Kir2) are key proteins that set the threshold for the beating of a heart. The Hansen lab has found that cholesterol sequesters Kir2 from its activating lipid phosphatidylinositol 4,5 bis phosphate (PIP2). Low mechanical shear and polyunsaturated fatty acids disrupt the cholesterol allowing the channel to bind to PIP2 and set the threshold of cardiac contractions. These findings help explain why exercise (increased blood flow) and diets high in PUFAS are benefit your heart.