Scott Hansen, Ph.D.
Ph.D., University of California, San Diego, 2005
Department of Molecular Medicine
Department of Neuroscience
The Scripps Research Institute
130 Scripps Way C236
Jupiter, Florida 33458
Membrane proteins, and ion channels in particular, are important molecular switches that control nerve cell activity in the brain. Ion channels are drug targets for the treatment of brain afflictions including addiction, pain, depression, and loss of consciousness. My lab employs membrane protein crystallography, electrophysiology, and pharmacology to understand ion channel activation and develop receptor-selective compounds for the treatment of neurological disease.
My research is uniquely situated at the interface of ion channel regulation and lipid signaling. Recent findings, including my own, suggest that lipids bind to and modulate ion channels by chemical means analogous to classical agonists or neurotransmitters. The number of ion channels inhibited or activated by lipids is extensive; they include the Kir, Kv, hERG, Slo, K2P, CNG, ENaC, TRP, P2X, nAChR, and GABA channels. We are developing the tools to answer important biophysical questions about lipid regulation of ion channels.
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.
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
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, 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
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
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
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
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
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):36066-70Hansen SB, Xiao Tao, Roderick MacKinnon “Structural basis of PIP2 activation of the classical inward rectifier K+ channel Kir2.2” Nature 2011, 477:495-98
Awards, Recognition, Appointments, and Honors
2003-2005 Dissertation Fellowship, Tobacco Related Disease Research Program Young Scientist
2006 Travel Award, American Society of Pharmacology and Experimental Therapeutics
2006 Martin D. Kamen Award, best doctoral thesis; University of California, San Diego
2007-2011 Postdoctoral Fellowship, Howard Hughes Medical Institute