research area

Nashaat Gerges, PhD

Nashaat Gerges, PhD, BPharm

Associate Professor
Interim Chair of the Department of Biopharmaceutical Sciences

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Cellular and molecular mechanisms of synaptic plasticity

 

Communication between neuronal cells in the brain occurs through tiny contacts called synapses. The ability of these synapses to change their strength and remodel is termed synaptic plasticity, which is thought to be the cellular correlate of learning and memory. Several neurological and neurodegenerative diseases (e.g., Alzheimer's disease, schizophrenia and mental retardation) as well as some hormonal and homeostasis abnormalities (e.g., hypothyroidism and stress) have some form of synaptic plasticity malfunction. The research in the laboratory is focused on elucidating the molecular and cellular mechanism of synaptic plasticity, and the associated changes in the disease states.

The major experimental approach is the expression of recombinant neurotransmitter receptors and regulatory proteins tagged with GFP or RFP in organotypic hippocampal cultured slices or in vivo. In order to understand how these regulatory molecules contribute to neuronal function, the lab uses a combination of in vivo and ex vivo electrophysiology, biochemistry, confocal imaging and electron microscopy (EM) analysis.


Electrophysiological whole-cell double recording configuration

Electrophysiological whole-cell double recording configuration. Stimulation of Schaffer collateral pathway and simultaneous recording from a control cell and a neuron expressing a regulatory molecule.

 

 

 

 

 

 

 

 

 

Confocal microscopy imagesConfocal microscopy images for a neuron expressing GluR2-GFP and a regulatory protein tagged with RFP. Immunohistochemistry enables visualizing the surface recombinant receptors (Cy5).

 

 

 

 

 

 

 

 

 

 

 

Electron microscopy micrographsElectron microscopy micrographs of GluR2/3 gold immunolabeling at hippocampal CA1 synapses. * denotes presynaptic terminals; PSD is the postsynaptic density.

 

 

 

 

 

 

 

 

 

 

 

Selected Publications

 

Brown JC, Petersen A, Zhong L, Himelright ML, Murphy JA, Walikonis RS, Gerges NZ.   Bidirectional regulation of synaptic transmission by BRAG1/IQSEC2 and its requirement in long-term depression.   Nat Commun.   2016 Mar 24;7:11080.

Knafo S, Sánchez-Puelles C, Palomer E, Delgado I, Draffin JE, Mingo J, Wahle T, Kaleka K, Mou L, Pereda-Perez I, Klosi E, Faber EB, Chapman HM, Lozano-Montes L, Ortega-Molina A, Ordóñez-Gutiérrez L, Wandosell F, Viña J, Dotti CG, Hall RA, Pulido R, Gerges NZ, Chan AM, Spaller MR, Serrano M, Venero C, Esteban JA.   PTEN recruitment controls synaptic and cognitive function in Alzheimer's models.   Nat Neurosci.   2016 Mar;19(3):443-53.

Kaleka KS, Gerges NZ.   Neurogranin restores amyloid β-mediated synaptic transmission and long-term potentiation deficits.   Exp Neurol.   2016 Mar;277:115-23.

Santarriaga S, Petersen A, Ndukwe K, Brandt A, Gerges N, Bruns Scaglione J, Scaglione KM.   The Social Amoeba Dictyostelium discoideum Is Highly Resistant to Polyglutamine Aggregation.   J Biol Chem.   2015 Oct 16;290(42):25571-8.

Petersen A, Gerges NZ.   Neurogranin regulates CaM dynamics at dendritic spines.   Sci Rep.   2015 Jun 18;5:11135.

Zhong L, Brown J, Kramer A, Kaleka K, Petersen A, Krueger JN, Florence M, Muelbl MJ, Battle M, Murphy GG, Olsen CM, Gerges NZ.   Increased prefrontal cortex neurogranin enhances plasticity and extinction learning.   J Neurosci.   2015 May 13;35(19):7503-8.

Zhong L, Brown JC, Wells C, Gerges NZ.   Post-embedding Immunogold labeling of synaptic proteins in hippocampal slice cultures.   J Vis Exp.   2013 Apr 03(74).

Kumar V, Chichili VP, Zhong L, Tang X, Velazquez-Campoy A, Sheu FS, Seetharaman J, Gerges NZ, Sivaraman J.   Structural basis for the interaction of unstructured neuron specific substrates neuromodulin and neurogranin with Calmodulin.   Sci Rep.   2013;3:1392.

Shin SM, Zhang N, Hansen J, Gerges NZ, Pak DT, Sheng M, Lee SH.   GKAP orchestrates activity-dependent postsynaptic protein remodeling and homeostatic scaling.   Nat Neurosci.   2012 Dec;15(12):1655-66.

Garrison SR, Kramer AA, Gerges NZ, Hillery CA, Stucky CL.   Sickle cell mice exhibit mechanical allodynia and enhanced responsiveness in light touch cutaneous mechanoreceptors.   Mol Pain.   2012 Sep 10;8:62.

Zhong L, Gerges NZ.   Neurogranin targets calmodulin and lowers the threshold for the induction of long-term potentiation.   PLoS One.   2012;7(7):e41275.

Danielson E, Zhang N, Metallo J, Kaleka K, Shin SM, Gerges N, Lee SH.   S-SCAM/MAGI-2 is an essential synaptic scaffolding molecule for the GluA2-containing maintenance pool of AMPA receptors.   J Neurosci.   2012 May 16;32(20):6967-80.


Publications of Nashaat Gerges PhD from the Faculty Collaboration Database