Hansen Lab, Institute for Medical Physiology

The Hansen lab studies the molecular basis of pain and Alzheimer’s Disease. We focus on the molecular mechanisms resulting in hyper-excitability (over activation) of cells. Over activation of cells gives rise to unwanted pain and anxiety and can cause cell death giving rise to neurodegeneration, diabetes, and autoimmune disease.

Treatments for these diseases are shockingly limited, and their limits have been exasperated by a lack of molecular understanding. Solving this problem is a major scientific endeavor.

The Hansen lab has established an important underlying mechanism for excitability based on cholesterol. The cholesterol sets the threshold for spatial distribution of proteins, and the spatial distribution dictates the proteins’ function. By studying the function of molecules in their 2D state (spatial biology) the Hansen lab has established a molecular basis for inhaled anesthesia, membrane mediated mechanosensation, and amyloid production in AD. These discoveries are being translated into drug discovery endeavors to treat disease.

Scott B. Hansen

Scott B. Hansen is a principal investigator at the Chinese Institutes for Medical Research (CIMR) in Beijing, with appointments in the Institutes for Medical Physiology and at capital medical university. Scott completed his doctoral training at the University of California, San Diego, and then went on to train with Rod Mackinnon at The Rockefeller University and Loren Walensky at Harvard before starting his own lab at Scripps Research (USA) in 2012. In 2024 Scott moved his lab to CIMR where he continues his studies on membrane mediated anesthesia, neurodegeneration, and the excitability of cells. Outside of lab, Scott likes piano and sports, in particular surfing, running, and skiing.

Chinese Institute for Medical Research, Beijing.

RESEARCH

Role of Cholesterol in Alzheimer’s disease

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.

Molecular Mechanism of membrane-mediated general anesthesia

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.

The role of cholesterol in cardiac disease

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.

Team