Dr. Thayer's laboratory studies neurodegenerative processes. His group uses electrophysiological and optical techniques to measure ion currents, to image synaptic proteins and to record changes in intracellular calcium within single neurons grown in tissue culture. Current research efforts focus on three principal areas.
1) 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. Thus, neurons have developed a complex system to maintain calcium homeostasis. Current studies focus on the modulation of processes that remove calcium from the cytoplasm by drugs and second messengers.
2) Synapse loss occurs early in neurodegenerative disease and correlates with cognitive decline in patients with HIV-1 associated dementia and Alzheimer's disease. Recent studies indicate that loss of synapses is not an early step leading to the cell's demise but instead, is a coping mechanism to reduce excess excitotoxic input. Current studies employ in vitro models to evaluate pharmacological strategies to prevent loss or induce recovery of synapses during neurotoxic processes.
3) Cannabinoids, analogs of the psychoactive ingredient in marijuana, act on receptors that are part of an endogenous signaling system. Endocannabinoid signaling serves as an on-demand neuroprotective mechanism. Currents studies examine the role of the endocannabinoid system in regulating synaptic transmission and neurotoxicity.
Drugs to slow the progression of neurodegenerative disease are lacking. Agents that modulate calcium signals, possibly via the endocannabinoid system, may protect synapses and cells from neurotoxic insult.
(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)
- Zhang X, Thayer SA. onoacylglycerol lipase inhibitor JZL184 prevents HIV-1 gp120-induced synapse loss by altering endocannabinoid signaling. Neuropharmacology. 2018;128:269-281.
- Strehler EE, Thayer SA. Evidence for a role of plasma membrane calcium pumps in neurodegenerative disease: Recent developments. Neurosci Lett. 2017 Aug 19. pii: S0304-3940(17)30682-1.
- Raybuck JD, Hargus NJ, Thayer SA. A GluN2B-selective NMDAR antagonist reverses synapse loss and cognitive impairment produced by the HIV-1 protein Tat. J Neurosci. 2017;37(33):7837-7847.
- Green MV, Thayer SA. NMDARs adapt to neurotoxic HIV protein Tat downstream of a GluN2A-ubiquitin ligase signaling pathway. J Neurosci. 2016;36(50):12640-12649.
- Ghosh B, Green MV, Krogh KA, Thayer SA. Interleukin-1β activates a Src family kinase to stimulate the plasma membrane Ca2+ pump in hippocampal neurons. J Neurophysiol. 2016;115(4):1875-85
- Krogh KA, Lyddon E, Thayer SA. HIV-1 Tat activates a RhoA signaling pathway to reduce NMDA-evoked calcium responses in hippocampal neurons via an actin-dependent mechanism. J Neurochem. 2015;132(3):354-66.
- Krogh KA, Green MV, Thayer SA. HIV-1 Tat-induced changes in synaptically-driven network activity adapt during prolonged exposure.Curr HIV Res. 2014;12(6):406-14.
- Feng X, Krogh KA, Wu CY, Lin YW, Tsai HC, Thayer SA, Wei LN. Receptor-interacting protein 140 attenuates endoplasmic reticulum stress in neurons and protects against cell death. Nat Commun. 2014 Jul 28;5:4487.
- Krogh KA, Wydeven N, Wickman K, Thayer SA. HIV-1 protein Tat produces biphasic changes in NMDA-evoked increases in intracellular Ca2+ concentration via activation of Src kinase and nitric oxide signaling pathways. J Neurochem. 2014;130(5):642-56.
- Shin AH, Kim HJ, Thayer SA. Subtype selective NMDA receptor antagonists induce recovery of synapses lost following exposure to HIV-1 Tat. Br J Pharmacol. 2012;166(3):1002-17.
- Baltgalvis KA, Jaeger MA, Fitzsimons DP, Thayer SA, Lowe DA, Ervasti JM. Transgenic overexpression of γ-cytoplasmic actin protects against eccentric contraction-induced force loss in mdx mice. Skelet Muscle. 2011;1(1):32.
- Kim HJ, Shin AH, Thayer SA. Activation of cannabinoid type 2 receptors inhibits HIV-1 envelope glycoprotein gp120-induced synapse loss. Mol Pharmacol. 2011;80(3):357-66.
- Ghosh B, Li Y, Thayer SA. Inhibition of the plasma membrane Ca2+ pump by CD44 receptor activation of tyrosine kinases increases the action potential afterhyperpolarization in sensory neurons. J Neurosci. 2011;31(7):2361-70.
Former Graduate Students:
Matthew Green (Neuroscience, University of Minnesota).
Mariah Wu (Neuroscience, University of Minnesota).
Former Graduate Students:
Jon Waataja (Ph.D. 2007, Neuroscience, University of Minnesota).
Brooke Kelley (Ph.D., Pharmacology, 2004). Postdoctoral Fellow Dept. of Physiology and Biophysics, University of Washington.
Daniel Kim (Ph.D., Pharmacology, 2000). Scientist, R and D Inc, Minneapolis, MN
Guang Jian 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