Jon Martin Lindstrom

faculty photo
The Trustee Professor in Neuroscience
Department: Neuroscience

Contact information
217 Stemmler Hall
36th & Hamilton Walk
Philadelphia, PA 19104-6074
Office: 215-573-2859
Fax: 215-573-2858
Graduate Group Affiliations
Education:
B.A. (Biology)
University of Illinois, 1967.
(Neurobiology Course)
Marine Biology Laboratory Woods Hole, Massachusetts, 1970.
Ph.D. (Biology)
University of California San Diego, California, 1971.
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Description of Research Expertise

RESEARCH INTERESTS
The structure and function of nicotinic acetylcholine receptors. The autoimmune response to nicotinic receptors which causes myasthenia gravis: what initiates it, the pathological mechanisms by which it impairs neurosmuscular transmission, and how to specifically suppress it. The mechanisms of the differing effects of nicotine on the many subtypes of receptor: activation, desensitization, channel block, increased synthesis, and decreased turnover. The physiological roles of nicotinic receptors in development of specific synaptic connections, synaptic plasticity in learning and memory, and non-neuronal tissues. The pathological roles of nicotinic receptors in myasthenia, dysautonomia, epilepsy, myopia, Alzheimer's disease, and addiction to tobacco.

RESEARCH TECHNIQUES
Monoclonal antibodies; affinity chromatography; cloning and expression of native and mutant cDNAs; electrophysiology, and ligand binding.

RESEARCH SUMMARY
We are studying the biochemical and antigenic structure of nicotinic receptors from human muscle and Torpedo electric organ. We investigate pathological mechanisms and specific immunosuppressive therapy of experimental autoimmune myasthenia gravis in rats induced by immunization with purified receptor.

We are also studying the structure and function of neuronal nicotinic receptors. These studies primarily involve expression of cloned human receptors in Xenopus oocytes and permanently transfected cell lines.

We are also studying the effects of acute and chronic exposure to nicotine on various subtypes of nicotinic receptors. Understanding these effects is important for explaining both the effects of nicotine in tobacco and the effects of nicotinic drugs which are being developed. These structures should also reveal mechanisms through which nicotinic receptors could influence development and synaptic plasticity. Receptors are normally exposed to acetylcholine for milliseconds, but can be exposed to nicotine for hours. Nicotine, like any agonist, initially activates and then desensitizes receptors. On prolonged exposure it increases assembly of receptor subunits and decreases turnover of receptors in the surface membrane. It can be a full or partial agonist and block the cation channel. All of these effects vary depending on the receptor subtype. Combinations of these effects on various receptor subtypes in various regions are responsible for addiction to nicotine, tolerance to some of its effects, and mediating its many effects, which range from enhanced cognition to reduced anxiety and pain.

Description of Itmat Expertise

Dr. Lindstrom is interested in developing a specific immunosuppressive therapy for myasthenia gravis.

We are also interested in developing a positive allosteric modulator for alpha 4 beta 2 alpha 5 nicotinic receptors for use in smoking cessation.

Selected Publications

Hone Arik J, Scadden Mick'l, Gajewiak Joanna, Christensen Sean, Lindstrom Jon M, McIntosh J Michael: α-Conotoxin PeIA[S9H,V10A,E14N] potently and selectively blocks α6β2β3 vs. α6β4 nicotinic acetylcholine receptors. Molecular pharmacology Aug 2012.

Luo, J, and Lindstrom, J.: Myasthenogenicity of the main immunogenic region and endogenous muscle acetylcholine receptors. Autoimmunity 45(3): 245-252, 2012.

Kuryatov A. and Lindstrom J.: Expression of Functional Human α6β2β3* AChRs in Xenopus Oocytes Achieved Through Subunit Chimeras and Concatamers Mol Pharmacol 79: 126-140, 2011

Yamauchi JG, Nemecz A, Nguyen QT, Muller A, Schroeder L, Talley TT, Lindstrom J, Kleinfeld D, Taylor P: Characterizing ligand-gated ion channel receptors with genetically encoded Ca++ sensors. PLoS ONE 6(1): e16519, January 2011.

Kuryatov A., Berrettini W., Lindstrom J.: AChR α5 Subunit Variant Associated With Risk for Nicotine Dependence and Lung Cancer Reduces (α4β2)2α5 AChR Function. Mol Pharmacol 79: 119-125, 2011.

Luo J, Lindstrom J.: Antigenic Structure of the Human Muscle Nicotinic Acetylcholine Receptor Main Immunogenic Region. J Mol Neurosci 40: 217-220, 2010.

Luo J, Kuryatov A, Lindstrom J: Specific immunotherapy of experimental myasthenia gravis by a novel mechanism. Annals of Neurology 67: 441-451, 2010.

Cheng S-B, Amici SA, Ren X-Q, McKay SB, Treuil MW, Lindstrom JM, Rao J, Anand R. : Presynaptic targeting of α4β2 nicotinic acetylcholine receptors is regulated by neurexin-1β J. Biol. Chem 284(35): 23251-59, August 2009

399. Rezvani K, Teng Y, Pan Y, Dani JA, Lindstrom J, Garcia Gras EA, McIntosh J, De Biasi M: UBXD4, a UBX containing protein, regulates the cell surface number and the stability of α3-containing nicotinic acetylcholine receptors. J Neurosci 29(21): 6883-6896, May 2009

Luo J, Taylor P, Losen M, de Baets MH, Shelton GD, Lindstrom J. : Main immunogenic region structure promotes binding of conformation-dependent myasthenia gravis autoantibodies, nicotinic acetylcholine receptor conformation maturation, and agonist sensitivity. J Neurosci. 29: 13898-908, 2009

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Last updated: 09/28/2012
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