Scott Hansen, PhD

Associate Professor
Department of Molecular Medicine
Florida Campus


 Email

Scripps Research Joint Appointments

Department of Neuroscience
Faculty, Graduate Program

Research Focus

My lab studies the molecular basis of pain thresholds and anesthesia in order to develop better medication for treating chronic pain. Current treatments for chronic pain rely on opioids. We focus on mechanosensitive (pain sensing) and anesthetic channels down stream of opioid receptors. Anesthetics reversibly and potently block pain. Mechanosensation is a process of generating the pain. By understanding these two process (mechanosensation and anesthesia) we have defined novel molecular pathways that intersect in modulating pain. We then use that knowledge to develop drug screening assays for developing pain medications.

 My lab has shown a novel mechanism for mechanosensation and anesthesia based on lipid membrane disruption. We have shown both anesthetics and mechanical force disrupt clustering of ordered lipids and this disruption gives rise to mechanosensation and anesthetic sensitivity in ion channels. We use a unique set of biophysical techniques to understand anesthetic action and mechanosensation. These techniques include super resolution imaging (dSTORM), electrophysiology, and ion channel pharmacology to understand the mechanism of ion channel activation and develop receptor-selective compounds for the treatment of neurological disease.

 My research is situated at the interface of ion channel regulation, membrane structure, and lipid signaling. Lipids coordinate intrinsic excitability of a cell through direct interactions of ion channels. The number of ion channels inhibited or activated by lipids is extensive; they include the Kir, Kv, hERG, Slo, K2P, CNG, ENaC, TRP, P2X, and nAChR channels. We are developing the tools to answer important biophysical questions about lipid regulation of ion channels. Specifically, how do lipids in a membrane interact with proteins to regulate the transport of ion across a biological membrane? And how can we use these sites of regulation to cure disease.

 A position is available to study pain and the development of opioid alternatives. Individuals, who are interested in joining the lab, please email Scott Hansen. Postdoc applicants with experinence in protien purification or pharmacology are particularly encouraged to apply. 


Education

Ph.D., University of California, San Diego, 2006
B.S. (Chemistry), Utah State University, 1999

Professional Experience

2017-2018 Assistant Professor, Molecular Medicine, Scripps Research
2012-2018 Assistant Professor (Joint Appointment), Neuroscience, Scripps Research
2012-2017 Assistant Professor, Molecular Therapeutics, Scripps Research
2000-2000 Research Associate, Scripps Research
1999-2000 Laboratory Technician, Abbott Laboratories

Awards & Professional Activities

Eicosanoid Research Foundation 2017 Young Investigator Award
NIH Director's New Innovator Award, DP2 (2013)
Postdoctoral Fellowship (2007-2011) Howard Hughes Medical Institute
Martin D. Kamen Award (2006), best doctoral thesis; University of California, San Diego
Young Scientist Travel Award (2006) American Society of Pharmacology and Experimental Therapeutics
Dissertation Fellowship (2003-2005) Tobacco Related Disease Research Program

Selected References

All Publications

Pavel MA, Chung HW, Petersen EN., Hansen SB. Polymodal Mechanism for TREK-1 Inhibition by Local Anesthetic (2019 in press) Anesth. & Analg.

Robinson CV, Rohacs T, and Hansen SBTools for understanding nanoscale lipid regulation of ion channels. TIBS, 2019 (In press)

Hae-Won Chung JMB 2018 Chung HW, Petersen EN, Cabanos C, Murphy KR, Pavel AP, Hansen AS, Ja WW, Hansen SB (2018) A Molecular Target for an Alcohol Chain-length Cutoff JMB (in press) https://doi.org/10.1016/j.jmb.2018.11.028

Mahmud Arif PavelE. Nicholas PetersenRichard A. LernerScott B. Hansen "Studies on the mechanism of general anesthesia. " Biorxiv 2018 https://doi.org/10.1101/313973

Nayebosadri, Arman and Petersen, E. Nicolas and Cabanos, Cerrone and Hansen, Scott B., A Membrane Thickness Sensor in TREK-1 Channels Transduces Mechanical Force (2018). Available at SSRN: https://ssrn.com/abstract=3155650 or http://dx.doi.org/10.2139/ssrn.3155650

Cabanos C, Wang M, Han X, Hansen SB (2017) A Soluble Fluorescent Binding Assay Reveals PIP2 Antagonism of TREK-1 Channels. Cell Rep 20(6):1287–1294.

E. Nicholas Peteresen, Hae-Wng Chung, Arman Nayebosadri, and Scott B. Hansen "Kinetic disruption of lipid rafts is a mechanosensor for phospholipase D" Nature Commun. 2016 Dec (7) 13873; doi: 10.1038/ncomms13873. PubMed PMID: 27976674

Hansen SB “Lipid Agonism; the PIP2 Paradigm of ligand gated ion channels” Biochim Biophys Acta 2015 May 1851 (5): 620-628. 

Hansen SB, Xiao Tao, Roderick MacKinnon “Structural basis of PIP2 activation of the classical inward rectifier K+ channel Kir2.2” Nature 2011, 477:495-98

Hansen SB, Wang, HL, Taylor P, and Sine SM “An Ion-Selectivity Filter in the Extracellular Domain of Cys-loop Receptors Reveals Determinants for Ion Conductance. J Biol Chem. 2008 Dec 26:283(52):36066-70

Hansen SB and Taylor P “Galanthamine and Non-competitive Inhibitor Binding to ACh-binding Protein: Evidence for a Binding Site on Non-a-subunit Interfaces of Heteromeric Neuronal Nicotinic Receptors” J. Mol. Biol. 2007 June 369, 895-901 

Gao F, Mer G, Tonelli M, Hansen SB, Burghart TP, Taylor P, Sine SM. “Solution NMR of Acetycholine Binding Protein Reveals ACh-mediated Conformational Change of the C-loop” Mol Pharmacol. 2006 Oct 70(4): 1230-5

Bourne Y, Talley TT, Hansen SB, Taylor P and Marchot P “Crystal structure of a Cbtx-AChBP complex reveals essential interaction between snake a-neurotoxins and nicotinic receptors” Embo J 2005, 24: 1512-22

Hibbs RE, Johnson DA, Shi J, Hansen SB, and Taylor P “Structural Dynamics of the a-Neurotoxin-Acetylcholine Binding Protein Complex: Hydrodynamic and Fluorescence Anisotropy Decay Analyses” Biochemistry 2005, 44:16602-11

Hansen SB, Sulzenbacher G, Huxford T, Marchot P, Taylor P, and Bourne Y “Structures of Aplysia AChBP complexes with agonists and antagonists reveal distinctive binding interfaces and conformations” Embo J 2005, 24:3635-46

Gao F, Bren N, Burghardt TP, Hansen SB, Henchman RH, Taylor P, McCammon JA, Sine SM. “Agonist-mediated conformational changes in acetylcholine-binding protein revealed by simulation and intrinsic tryptophan fluorescence” J Biol Chem. 2005 Mar 4;280(9):8443-51

Bouzat C, Gumilar F, Spitzmaul G, Wang HL, Rayes D, Hansen SB, Taylor P, and Sine SM “Coupling of agonist binding to channel gating in an ACh-binding protein linked to an ion channel” Nature 2004 Aug 19:430:896-900

Hansen SB, Talley TT, Radic Z, and Taylor P. “Structural and ligand recognition characteristics of an acetylcholine binding protein from Aplysia californica” J Biol Chem. 2004 Jun 4:279(23):24197-202

Gao F, Bern N, Little A, Wang HL, Hansen SB, Talley TT, Taylor P, and Sine SM. “Curariform antagonists bind in different orientations to acetylcholine-binding protein” J Biol Chem. 2003 Jun 20;278(25):23020-6.

Hansen SB, Radic Z, Talley TT, Molles BE, Deerinck T, Tsigelny I, and Taylor P. “Tryptophan fluorescence reveals conformational changes in the acetylcholine binding protein” J Biol Chem. 2002 Nov 1;277(44):41299-302.

Issued Patents

Hansen SB, Radic Z, and Taylor P “Methods for identifying agents that modulate LGIC receptor activity.” United States Patent 7947466. 24 May 2011

Hansen SB, Hansen AS "Methods for identifying molecules that modulate lipid binding sites of ion channels" United States Patent 8669065. 11 March 2014 


Links

New Innovator Award 2013

Pubmed Citations

Neuroscience page

Press release, Appointment

Faculty of 1000

Webvision: notable paper

Google Scholar