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Eric C. Beattie, PhD
Email: Beattie@cpmcri.org

Research Focus  |  Experience and Objectives  |  Publications 


Research Focus

My lab focuses on how neurons communicate through various neurotransmitter receptors (eg- the AMPA-type glutamate receptors (AMPARs)). When AMPARs are properly localized on the surface of the neuron, they are ready to receive messages from neighboring neurons which come in the form of chemical neurotransmitter proteins (eg- glutamate). Tight control over the proper amount or volume of this communication between neurons is vital for proper brain function. Injury and disease in the brain or spinal cord lead to inflammation and this can increase the volume of the glutamatergic conversation between neurons by increasing the surface localization of AMPARs. When too many AMPARs are placed on the neuron surface, the volume of this conversation becomes too great, and neurons begin to self-destruct through a calcium-mediated process. Our studies are beining to uncover the components of the inflammatory process which lead to this increased surface expression of AMPARs (eg- TNFα), and what interventions might control this activity (eg- PI3K inhibitors). A more complete understanding of this process will help in the search for drug targets aimed at protecting neurons after acute brain trauma or during neurodegenerative diseases. Techniques that we use and have developed in-house include biochemical and quantitative immunohistochemical analysis of receptor subcellular localization. This includes real-time live imaging of receptor exocytosis in living neurons. We also are expert in the measurment of neuron death (LDH and PI analysis of neuroexcitotoxicity in vitro).



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Experience and Objectives

I plan to continue leading an outstanding international group of postdocs, students, technicians, and volunteers so that we may discover drug targets that will protect neuron health and function during neurodegenerative diseases or after acute neurotrauma. I will apply my neuroscience experience of over 20 years to lead this group. This experience includes 3 years in the biotech industry, 18 years in academia, and the last 7 years of leading my own independent research lab. My lab’s focus has been the interaction of the central nervous system and the immune system. Most recently, I have investigated how the inflammatory process (TNFα in particular) increases the surface expression of AMPA-type glutamate receptors in neurons and how this increases the excitotoxic vulnerability of neurons (see publications).
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Publications 

Click here for a List of publications by Eric C Beattie in PubMed.

Selected Publications:

Pingwei Zhao, Dmitri Leonoudakis, Mary E. Abood*, and Eric Beattie* (*these senior authors contributed equally to this work). Cannabinoid Receptor Activation Reduces TNFα-Induced Surface Localization of AMPAR-Type Glutamate Receptors and Excitotoxicity. Neuropharmacology (in press).

Pingwei Zhao, Sheila Ignacio, Eric C. Beattie* and Mary E. Abood*
(*equal senior authors). Altered presymptomatic AMPA and cannabinoid receptor trafficking in motor neurons of ALS model mice: implications for excitotoxicity. European Journal of Neuroscience. 2008 Feb;27(3):572-9.

Dmitri Leonoudakis, Pingwei Zhao, and Eric C. Beattie. Rapid TNF-induced exocytosis of GluR2-lacking AMPARs to extrasynaptic plasma membrane potentiates excitotoxicity. The Journal of Neuroscience, 2008 Feb 27;28(9):2119-30.

Eric C. Beattie and David Stellwagen. AMPAR Synaptic and Surface Localization Is Altered by Glial-Derived Tumor Necrosis Factor Alpha: Relevance to Hyperalgesia and Central Sensitization. Part IV, Chapter 12. Invited authorship book chapter featured in Immune and Glial Regulation of Pain, edited by Linda Watkins, Joyce DeLeo, and Linda Sorkin. Seattle: International Association for the Study of Pain Press. ISBN-10 0-931092-67-1. This book is available for purchase at: http://www.iasp-pain.org/.

Guillermo A. Yudowski, Manojkumar A. Puthenveedu, Dmitri Leonoudakis, Sandip Panicker, Kurt S. Thorn, Eric C. Beattie and Mark von Zastrow. Real-time imaging of discrete exocytic events mediating surface delivery of AMPA receptors. J Neurosci. 2007 Oct 10;27(41):11112-21.

Zhu J, Beattie EC, Yang Y, Wang HJ, Seo JY, Yang XL. Centrosome impairments and consequent cytokinesis defects are possible mechanisms of taxane drugs. Anticancer Research. 2005 May-Jun;25(3B):1919-25.

Stellwagen D, Beattie EC, Seo JY, Malenka RC. Differential regulation of AMPA receptor and GABA receptor trafficking by tumor necrosis factor . Journal of Neuroscience, 2005 Mar 23;25(12):3219-28.

Leonoudakis D, Braithwaite SP, Beattie MS, Beattie EC. TNF-induced AMPAR trafficking in CNS neurons; relevance to excitotoxicity. Neuron Glia Biology, 2004 Aug;1(3):263-273.

Beattie EC, Stellwagen S, Morishita W, Bresnahan JC, Byeong-Kung Ha, Von Zastrow M, Beattie MS, Malenka RC. Control of Synaptic Strength by Glial TNF Science. Vol. 295, March 22, 2002.

Carroll RC, Beattie EC, von Zastrow M, Malenka RC. Role of AMPA Receptor Endocytosis In Synaptic Plasticity. Nature Neuroscience Reviews. May, 2001.

Beattie EC, Carroll RC, Yu X, Morishita W, Yasuda H, von Zastrow M, Malenka RC. Regulation of AMPA receptor endocytosis by a signaling mechanism shared with LTD. Nature Neuroscience 2000 Dec;3(12):1291-300.

Beattie EC, Howe CL, Wilde A, Brodsky FM, Mobley WC. NGF signals through TrkA to increase clathrin at the plasma membrane and enhance clathrin-mediated membrane trafficking. Journal of Neuroscience 2000 Oct 1;20(19):7325-33.

Whistler J, Beattie EC, and von Zastrow M. Tales from the Crypt: Evidence for Heptahelical Receptor Signaling in the Endocytic Pathway. Science Magazine's Signal Transduction Knowledge Environment: 2000 Aug 29,

Luscher C, Xia H, Beattie EC, Carroll RC, von Zastrow M, Malenka RC, Nicoll RA. Role of AMPA receptor cycling in synaptic transmission and plasticity. Neuron 1999 Nov;24(3):649-58.

Carroll RC, Beattie EC, Xia H, Luscher C, Altschuler Y, Nicoll RA, Malenka RC, von Zastrow M. Dynamin-dependent endocytosis of ionotropic glutamate receptors. Proc Natl Acad Sci U S A 1999 Nov 23;96(24):14112-

Wilde A, Beattie EC, Lem L, Riethof DA, Liu SH, Mobley WC, Soriano P, Brodsky FM. EGF receptor signaling stimulates SRC kinase phosphorylation of clathrin, influencing clathrin redistribution and EGF uptake. Cell 1999 Mar 5;96(5):677-87.

Grimes ML, Zhou J, Beattie EC, Yuen EC, Hall DE, Valletta JS, Topp KS, LaVail JH, Bunnett NW, Mobley WC. Endocytosis of activated TrkA: evidence that nerve growth factor inducesformation of signaling endosomes. J Neurosci 1996 Dec 15;16(24):7950-64

Grimes ML, Beattie E, WC Mobley. A signaling organelle containing the nerve growth factor-activated receptor tyrosine kinase, TrkA.
Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9909-14.

Beattie EC, Zhou J, Grimes ML, Bunnett NW, Howe CL, Mobley WC. A signaling endosome hypothesis to explain NGF actions: potential implications for neurodegeneration. Cold Spring Harb Symp Quant Biol 1996;61:389-406.
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Eric
Eric C. Beattie, PhD
Associate Scientist, Neurosciences Program
California Pacific Medical Center Research Institute
475 Brannan St. Suite 220
San Francisco, CA 94107

415 600-1185 (office)
415 218-4191 (cell)
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