Scott Hansen, Ph.D.
Associate Professor Of Department Of Molecular Medicine
About Scott Hansen
Our laboratory studies the role of cholesterol in setting thresholds of anesthesia, mechanosensation, amyloid formation, and viral entry. In each area of research, we study how cholesterol controls the threshold that regulates biological function and the severity of disease. By understanding the thresholds, we aim to treat diseases caused by altered cholesterol levels and signaling lipids.
Anesthesia: For hundred years scientist believed that membrane lipids were involved in the anesthesia (reversible loss of consciousness). At the heart of the question was the following, How can disrupting a lipid membrane activate or inhibit and ion channel? We have shown that anesthetics disrupt compartmentalization of signaling molecules in cholesterol dependent lipid compartments. The anesthetics counteract cholesterol causing the proteins to escape and activate an ion channel. This established at least one clear molecular mechanism for the membrane as a target of inhaled anesthetics. We are studying this mechanism for additional ion channels that mediate anesthesia in people.
Pain threshold (mechanosensation): We have shown mechanical force disrupts cholesterol dependent compartmentalization of proteins, similar to anesthetics. In addition to defining a novel mechanosensation pathway, we are developing potential therapeutic compounds that will activate an analgesic channel downstream of mu opioid receptor. We aim to develop therapeutics that will have similar pain reducing benefits as opioids, but without the addiction.
Viral entry: We have recently proposed a model for cholesterol dependent SARS-COV-2 viral infectivity, based on our understanding of cholesterol mediated membrane protein translocation. As cholesterol increases the ability of the virus to enter the cell increases. Increased viral entry increases inflammation, which in turn increases cholesterol and more viral entry. We are currently studying cholesterol loading in lung tissues in aged animals.
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