Scott Hansen

Scott Hansen, Ph.D.

Associate Professor Of Department Of Molecular Medicine

Department: SR-MM-HANSEN LAB
Business Phone: (561) 228-2415
Business Email: hansen.scott@ufl.edu

About Scott Hansen

Related Links:
Additional Positions:
Assistant Professor, Molecular Medicine
2017 – 2018 · Scripps Research
Assistant Professor (Joint Appointment), Neuroscience
2012 – 2018 · Scripps Research
Assistant Professor, Molecular Therapeutics
2012 – 2017 · Scripps Research
Research Associate
2000 – 2000 · Scripps Research
Laboratory Technician
1999 – 2000 · Abbott Laboratories

Research Profile

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.

Publications

2021
Regulation of beta-amyloid production in neurons by astrocyte-derived cholesterol.
Proceedings of the National Academy of Sciences of the United States of America. [DOI] 10.1073/pnas.2102191118. [PMID] 34385305.
2021
The role of high cholesterol in age-related COVID19 lethality.
bioRxiv : the preprint server for biology. [DOI] 10.1101/2020.05.09.086249. [PMID] 32511366.
2020
Disruption of palmitate-mediated localization; a shared pathway of force and anesthetic activation of TREK-1 channels.
Biochimica et biophysica acta. Biomembranes. [DOI] 10.1016/j.bbamem.2019.183091. [PMID] 31672538.
2020
Hydroxychloroquine: mechanism of action inhibiting SARS-CoV2 entry.
bioRxiv : the preprint server for biology. [DOI] 10.1101/2020.08.13.250217. [PMID] 32817933.
2020
Reply to van Swinderen and Hines: Drosophila model establishes the lipid membrane as a target of anesthetics.
Proceedings of the National Academy of Sciences of the United States of America. [DOI] 10.1073/pnas.2015732117. [PMID] 32994344.
2020
Studies on the mechanism of general anesthesia.
Proceedings of the National Academy of Sciences of the United States of America. [DOI] 10.1073/pnas.2004259117. [PMID] 32467161.
2019
A Molecular Target for an Alcohol Chain-Length Cutoff.
Journal of molecular biology. [DOI] 10.1016/j.jmb.2018.11.028. [PMID] 30529033.
2019
Polymodal Mechanism for TWIK-Related K+ Channel Inhibition by Local Anesthetic.
Anesthesia and analgesia. [DOI] 10.1213/ANE.0000000000004216. [PMID] 31124840.
2017
A Soluble Fluorescent Binding Assay Reveals PIP2 Antagonism of TREK-1 Channels.
Cell reports. [DOI] 10.1016/j.celrep.2017.07.034. [PMID] 28793254.
2016
Kinetic disruption of lipid rafts is a mechanosensor for phospholipase D.
Nature communications. [DOI] 10.1038/ncomms13873. [PMID] 27976674.
2015
Lipid agonism: The PIP2 paradigm of ligand-gated ion channels.
Biochimica et biophysica acta. [DOI] 10.1016/j.bbalip.2015.01.011. [PMID] 25633344.
2011
Structural basis of PIP2 activation of the classical inward rectifier K+ channel Kir2.2.
Nature. [DOI] 10.1038/nature10370. [PMID] 21874019.
2006
Structural characterization of agonist and antagonist-bound acetylcholine-binding protein from Aplysia californica.
Journal of molecular neuroscience : MN. [PMID] 17192647.
2004
Coupling of agonist binding to channel gating in an ACh-binding protein linked to an ion channel.
Nature. [PMID] 15318223.

Grants

Apr 2022 ACTIVE
The role of lipid raft disruption in the activation of TREK-1 channels by anesthetics
Role: Principal Investigator
Funding: NATL INST OF HLTH NINDS

Contact Details

Phones:
Business:
(561) 228-2415
Emails:
Addresses:
Business Mailing:
Location C260
130 SCRIPPS WAY BLDG 2C1
JUPITER FL 33458