Research Interests:
Dr. Thayer's laboratory is studying the regulation
of the intracellular calcium concentration in neurons, and examining
the components of this system as potential pharmacologic targets.
Calcium is an essential second messenger involved in neurotransmitter
release, gene regulation, and synaptic plasticity. Inappropriate
elevation of the intracellular calcium concentration contributes
to the neurodegeneration associated with AIDS, ischemia, epilepsy
and head trauma.
Dr. Thayer's group uses electrophysiological and
optical techniques to measure membrane ion currents and the fluorescence
emitted by calcium-sensitive dyes in single neurons grown in tissue
culture. Current research efforts are directed to three principal
areas: 1) the processes which remove calcium from the cytoplasm
are studied with respect to their modulation by drugs and second
messenger systems; 2) in vitro models are used to evaluate strategies
to prevent calcium-induced neurodegeneration; and 3) the influence
of cannabinoid drugs on synaptic plasticity are studied.
Neurons have developed a complex system to maintain
calcium homeostasis. Drugs targeted to specific components of
this system are useful tools for studying signaling processes,
have profound effects on synaptic transmission and may prove to
be effective neuroprotective agents.
Selected Publications:
Waataja JJ, Kim HJ, Roloff AM, Thayer SA. Excitotoxic loss of post-synaptic sites is distinct temporally and mechanistically from neuronal death. J Neurochem. 2008 Jan;104(2):364-75.
Jackson JG, Usachev YM, Thayer SA. Bradykinin-induced nuclear factor of activated T-cells-dependent transcription in rat dorsal root ganglion neurons. Mol Pharmacol. 2007 Aug;72(2):303-10.
Gilbert GL, Kim HJ, Waataja JJ, Thayer SA. Delta9-tetrahydrocannabinol protects hippocampal neurons from excitotoxicity. Brain Res. 2007 Jan 12;1128(1):61-9.
Shideman, C. R. S. Hu, P.K. Peterson, and Thayer, S. A. (2006) CCL5 evokes calcium signals in microglia through a kinase, phosphoinositide and nucleotide-dependent mechanism J. Neurosci. Res. 83 :1471-84.
Usachev, Y. M., Marsh, A. J., Johanns, T. M., Lemke, M. M. and Thayer, S. A. (2006) Activation of Protein Kinase C in Sensory Neurons Accelerates Ca 2+ Uptake into the Endoplasmic Reticulum. J. Neurosci. 26 :311-318
Pottorf, W. J., Johanns, T. M, Derrington, S. M., Strehler, E. E., Enyedi, A., and Thayer, S. A. (2006) Glutamate-Induced Protease-Mediated Loss of Plasma Membrane Ca 2+ Pump Activity in Rat Hippocampal Neurons. J. Neurochem. 98 :1646-56.
Jackson, J. G. and Thayer, S. A. (2006) Mitochondrial Modulation of Ca 2+ -Induced Ca 2+ -Release in Rat Sensory Neurons. J. Neurophysiol. 96 :1093-104.
Kelley, B. K. and Thayer, S. A. (2004) delta 9 -Tetrahydrocannabinol antagonizes endocannabinoid modulation of synaptic transmission between hippocampal neurons in culture. Neuropharmacology 46 :709-715.
Kelley, B. K. and Thayer, S. A. (2004) Anandamide transport inhibitor AM404 and structurally related compounds inhibit synaptic transmission between rat hippocampal neurons in culture independent of CB1 receptors. Eur. J. Pharmacol. 496 33-39.
Former Graduate Students:
Jon Waataja (Ph.D. 2007, Neuroscience, University of Minnesota).
Guangjian Wang
(Ph.D. 1996, Neuroscience, University of Minnesota). Assistant Professor,
Department of Pediatrics,
Kosair Children's Hospital Research Institute,
University of Louisville
Timothy Piser (Ph.D., Pharmacology, 1995). Director
of Neuroscience Research, AstraZeneca Pharmaceuticals, Wilmington,
Delaware
John Werth (Ph.D., Pharmacology, 1994). Scientific
Liaison, Pfizer Inc., Ann Arbor, Michigan
Daniel Kim (Ph.D., Pharmacology, 2000). Scientist,
R and D Inc, Minneapolis, MN
Brooke Kelley (Ph.D., Pharmacology, 2004). Postdoctoral Fellow Dept. of Physiology and Biophysics, University of Washington.