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Gareth Thomas, PhD

Gareth Thomas, PhD


Assistant Professor, Anatomy and Cell Biology

Assistant Professor, Shriners Hospitals Pediatric Research Center

Telephone: 215-926-9355 (Internal: 7-9355)

Email: gareth.thomas@temple.edu


Anatomy and Cell Biology

Shriners Hospitals Pediatric Research Center


Educational Background:


BA (honors), University of Cambridge, United Kingdom, 1994


PhD, University of Dundee, United Kingdom, 1998


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professional affiliations:

  • Society for Neuroscience

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Neurons are structurally complex cells with unique spatial characteristics; their synaptic connections are often separated by only microns from one another, but their neurites can extend over huge distances. These features place unique demands on the spatial control of neuronal intracellular signaling and raise a key question: how do neurons spatially restrict some signals (e.g. to ensure synapse-specific regulation, which is critical for higher brain function), while conveying other signals over vast distances (e.g. to transfer retrograde signals from distal axons to neuronal cell bodies, a process that both sculpts the developing nervous system and also controls nerve regeneration after injury)?


This conundrum becomes even more vexing when one considers that most neuronal signaling events involve protein kinases. Many kinases are predicted to be diffusible cytosolic proteins that appear poorly suited to meet the demands of neuronal spatial regulation. However, our research suggests that an answer to the spatial signaling conundrum may lie in two novel ways in which neurons use palmitoylation, the covalent attachment of the lipid palmitate, to control kinase localization.


Palmitoylation can target proteins to specific membranes and has emerged as a key regulator of the localization of neurotransmitter receptors and non-enzymatic ‘scaffold’ proteins. However, we recently discovered that a select group of protein kinases is also directly palmitoylated. We have found that palmitoylation targets certain kinases to synapses, thus helping to explain how synapse-specific regulation is achieved. In addition, we have found that addition of the palmitate lipid can have a previously unrecognized function, allowing certain kinases to ‘hitchhike’ on trafficking vesicles and hence carry long distance signals. Moreover, we are also finding that palmitoylation can act not only as a ‘passive’ localization signal, but also as an ‘on switch’ to directly regulate kinase activity.


We use a multi-disciplinary approach to gain insights into these novel roles of palmitoylation, employing biochemical, molecular biological and cell biological techniques, together with state of the art cell imaging methods. We have developed novel palmitoylation assays, have custom-designed microfluidic chambers to facilitate our retrograde signaling studies and use cutting edge shRNA knockdown/rescue approaches to determine roles of palmitoyl-kinases both in cultured neurons and in vivo. Because several palmitoyl-kinases are closely linked to neuropathological conditions, we are hopeful that our studies may reveal new therapeutic approaches to treat a variety of disease conditions.


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Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

26460013. Hussain NK, Thomas GM, Luo J, Huganir RL, Regulation of AMPA receptor subunit GluA1 surface expression by PAK3 phosphorylation. Proc Natl Acad Sci U S A 112:43(E5883-90)2015 Oct 27

24068808. Thomas GM, Hayashi T, Huganir RL, Linden DJ, DHHC8-dependent PICK1 palmitoylation is required for induction of cerebellar long-term synaptic depression. J Neurosci 33:39(15401-7)2013 Sep 25

23356261. Thomas GM, Huganir RL, Palmitoylation-dependent regulation of glutamate receptors and their PDZ domain-containing partners. Biochem Soc Trans 41:1(72-8)2013 Feb 1

22325201. Thomas GM, Hayashi T, Chiu SL, Chen CM, Huganir RL, Palmitoylation by DHHC5/8 targets GRIP1 to dendritic endosomes to regulate AMPA-R trafficking. Neuron 73:3(482-96)2012 Feb 9

22285564. Pirooznia M, Wang T, Avramopoulos D, Valle D, Thomas G, Huganir RL, Goes FS, Potash JB, Zandi PP, SynaptomeDB: an ontology-based knowledgebase for synaptic genes. Bioinformatics 28:6(897-9)2012 Mar 15

21383172. Mejias R, Adamczyk A, Anggono V, Niranjan T, Thomas GM, Sharma K, Skinner C, Schwartz CE, Stevenson RE, Fallin MD, Kaufmann W, Pletnikov M, Valle D, Huganir RL, Wang T, Gain-of-function glutamate receptor interacting protein 1 variants alter GluA2 recycling and surface distribution in patients with autism. Proc Natl Acad Sci U S A 108:12(4920-5)2011 Mar 22

20956289. Mao L, Takamiya K, Thomas G, Lin DT, Huganir RL, GRIP1 and 2 regulate activity-dependent AMPA receptor recycling via exocyst complex interactions. Proc Natl Acad Sci U S A 107:44(19038-43)2010 Nov 2

20708684. Vieira M, Fernandes J, Burgeiro A, Thomas GM, Huganir RL, Duarte CB, Carvalho AL, Santos AE, Excitotoxicity through Ca2+-permeable AMPA receptors requires Ca2+-dependent JNK activation. Neurobiol Dis 40:3(645-55)2010 Dec

19874789. Hayashi T, Thomas GM, Huganir RL, Dual palmitoylation of NR2 subunits regulates NMDA receptor trafficking. Neuron 64:2(213-26)2009 Oct 29

18188153. Thomas GM, Lin DT, Nuriya M, Huganir RL, Rapid and bi-directional regulation of AMPA receptor phosphorylation and trafficking by JNK. EMBO J 27:2(361-72)2008 Jan 23

17761173. Ye B, Yu WP, Thomas GM, Huganir RL, GRASP-1 is a neuronal scaffold protein for the JNK signaling pathway. FEBS Lett 581:23(4403-10)2007 Sep 18

16543133. Steinberg JP, Takamiya K, Shen Y, Xia J, Rubio ME, Yu S, Jin W, Thomas GM, Linden DJ, Huganir RL, Targeted in vivo mutations of the AMPA receptor subunit GluR2 and its interacting protein PICK1 eliminate cerebellar long-term depression. Neuron 49:6(845-60)2006 Mar 16

16217014. Thomas GM, Rumbaugh GR, Harrar DB, Huganir RL, Ribosomal S6 kinase 2 interacts with and phosphorylates PDZ domain-containing proteins and regulates AMPA receptor transmission. Proc Natl Acad Sci U S A 102:42(15006-11)2005 Oct 18

14976517. Thomas GM, Huganir RL, MAPK cascade signalling and synaptic plasticity. Nat Rev Neurosci 5:3(173-83)2004 Mar

14741046. Sabio G, Reuver S, Feijoo C, Hasegawa M, Thomas GM, Centeno F, Kuhlendahl S, Leal-Ortiz S, Goedert M, Garner C, Cuenda A, Stress- and mitogen-induced phosphorylation of the synapse-associated protein SAP90/PSD-95 by activation of SAPK3/p38gamma and ERK1/ERK2. Biochem J 380:Pt 1(19-30)2004 May 15

10481074. Thomas GM, Frame S, Goedert M, Nathke I, Polakis P, Cohen P, A GSK3-binding peptide from FRAT1 selectively inhibits the GSK3-catalysed phosphorylation of axin and beta-catenin. FEBS Lett 458:2(247-51)1999 Sep 17

10212242. Hasegawa M, Cuenda A, Spillantini MG, Thomas GM, Buée-Scherrer V, Cohen P, Goedert M, Stress-activated protein kinase-3 interacts with the PDZ domain of alpha1-syntrophin. A mechanism for specific substrate recognition. J Biol Chem 274:18(12626-31)1999 Apr 30

9449999. Thomas GM, Haavik J, Cohen P, A stress-activated kinase cascade can mediate the activation of tyrosine hydroxylase in chromaffin cells. Biochem Soc Trans 25:4(S571)1997 Nov

7750576. Doza YN, Cuenda A, Thomas GM, Cohen P, Nebreda AR, Activation of the MAP kinase homologue RK requires the phosphorylation of Thr-180 and Tyr-182 and both residues are phosphorylated in chemically stressed KB cells. FEBS Lett 364:2(223-8)1995 May 8

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