Christos G. Gkogkas
The complex polygenic nature of brain disorders, such as neurodevelopmental disorders (Autism Spectrum Disorders, fragile X syndrome, intellectual disability) neuropsychiatric disorders (depression, schizophrenia) and neurodegenerative disorders (Parkinson's disease, Alzheimer's disease) along with the plethora of contributing non-genetic factors have impeded our efforts to understand and treat them. By studying converging signalling, molecular and cellular pathways, we can shed fresh light on the causality of brain disorders.
Proteins catalyse most of the reactions in the cell on which life depends. Translational control is defined as the sum of regulatory events that dictate changes in protein synthesis, per mRNA, per unit of time, and it is a powerful means to alter protein abundance. Our lab is particularly interested in understanding the molecular and signalling mechanisms of translational control in the brain and how they control complex brain functions and behaviours, such as learning, memory, social interactions, anxiety and fear and how they affect brain health (e.g.neurodegeneration).
Simbriger K, Amorim IS, Lach G, Chalkiadaki K, Kouloulia S, Jafarnejad SM, Khoutorsky A, Gkogkas CG. (2020) Uncovering memory-related gene expression in contextual fear conditioning using ribosome profiling. Prog Neurobiol. doi: 10.1016/j.pneurobio.2020.101903.
Kouloulia S, Hallin EI, Simbriger K, Amorim IS, Lach G, Amvrosiadis T, Chalkiadaki K, Kampaite A, Truong VT, Hooshmandi M, Jafarnejad SM, Skehel P, Kursula P, Khoutorsky A, Gkogkas CG. (2019) Raptor-Mediated Proteasomal Degradation of Deamidated 4E-BP2 Regulates Postnatal Neuronal Translation and NF-κB Activity. Cell Rep. 29:3620-3635.e7.
Amorim IS, Kedia S, Kouloulia S, Simbriger K, Gantois I, Jafarnejad SM, Li Y, Kampaite A, Pooters T, Romanò N, Gkogkas CG. (2018) Loss of eIF4E phosphorylation engenders depression-like behaviors via selective mRNA translation. J Neurosci. 38:2118-2133.
Gantois I, Khoutorsky A, Popic J, Aguilar-Valles A, Freemantle E, Cao R, Sharma V, Pooters T, Nagpal A, Skalecka A, Truong VT, Wiebe S, Groves IA, Jafarnejad SM, Chapat C, McCullagh EA, Gamache K, Nader K, Lacaille JC, Gkogkas CG, Sonenberg N. (2017) Metformin ameliorates core deficits in a mouse model of fragile X syndrome. Nat Med. 23:674-677.
Gkogkas CG, Khoutorsky A, Ran I, Rampakakis E, Nevarko T, Weatherill DB, Vasuta C, Yee S, Truitt M, Dallaire P, Major F, Lasko P, Ruggero D, Nader K, Lacaille JC, Sonenberg N. (2013) Autism-related deficits via dysregulated eIF4E-dependent translational control. Nature 493:371-377.
2020
Simbriger K, Amorim IS, Lach G, Chalkiadaki K, Kouloulia S, Jafarnejad SM, Khoutorsky A and Gkogkas C. G. Uncovering memory-related gene expression in contextual fear conditioning using ribosome profiling. Prog Neurobiol. 2020 Aug 26:101903. doi: 10.1016/j.pneurobio.2020.101903. (2020)
Atlasi Y, Jafarnejad SM, Gkogkas C. G., Vermeulen M, Sonenberg N, Stunnenberg HG. The translational landscape of ground state pluripotency. Nat Commun. 2020 Apr 1;11(1):1617. doi: 10.1038/s41467-020-15449-9. (2020)
2019
Hoang HD, Graber TE, Jia JJ, Vaidya N, Gilchrist VH, Xiang X, Li W, Cowan KN, Gkogkas C. G., Jaramillo M, Jafarnejad SM, Alain T. Induction of an Alternative mRNA 5' Leader Enhances Translation of the Ciliopathy Gene Inpp5e and Resistance to Oncolytic Virus Infection. Cell Rep. Dec 17;29(12):4010-4023.e5. doi: 10.1016/j.celrep.2019.11.072. (2019)
Kouloulia S, Hallin EI, Simbriger K, Amorim IS, Lach G, Amvrosiadis T, Chalkiadaki K, Kampaite A, Truong VT, Hooshmandi M, Jafarnejad SM, Skehel P, Kursula P, Khoutorsky A and Gkogkas C. G. Raptor-Mediated Proteasomal Degradation of Deamidated 4E-BP2 Regulates Postnatal Neuronal Translation and NF-κB Activity. Cell Rep. 2019 Dec 10;29(11):3620-3635.e7. doi: 10.1016/j.celrep.2019.11.023. (2019)
Simbriger K, Amorim IS, Chalkiadaki K, Lach G, Jafarnejad SM, Khoutorsky A and Gkogkas C. G.
Monitoring translation in synaptic fractions using a ribosome profiling strategy. J Neurosci Methods. 2020 Jan 1;329:108456. doi: 10.1016/j.jneumeth.2019.108456. Epub 2019 Oct 11. (2019)
2018
Amorim IS, Lach G and Gkogkas CG.
The Role of the Eukaryotic Translation Initiation Factor 4E (eIF4E) in Neuropsychiatric Disorders. Front Genet. 2018 Nov 23;9:561. doi: 10.3389/fgene.2018.00561. eCollection (2018).
Uttam, S., Wong, C, Amorim, I. S., Jafarnejad, S. M., Tansley, S., Yang, J., Prager-Khoutorsky, M., Mogil, J. S., Gkogkas, C. G.* and Khoutorsky, A.* Translational profiling of dorsal root ganglia and spinal cord in a mouse model of neuropathic pain. Neurobiology of pain Aug-Dec;4:35-44. doi: 10.1016/j.ynpai.2018.04.001. Epub 2018 Apr 18. (2018) *co-last author/co-corresponding
Amorim I.S., Kedia S., Kouloulia S., Simbriger K., Gantois I., Jafarnejad S. M., Li Y., Kampaite A., Pooters T., Romanò N and Gkogkas C. G. Loss of eIF4E phosphorylation engenders depression-like behaviors via selective mRNA translation. The Journal of neuroscience : the official journal of the Society for Neuroscience 21, 38(8):2118-2133. doi: 10.1523/JNEUROSCI.2673-17.2018 (2018).
Jafarnejad, S. M., Chapat, C., Matta-Camacho, E., Gelbart, I. A., Hesketh, G. G., Arguello, M., Garzia, A., Kim, S. H., Attig, J., Shapiro, M., Morita, M., Khoutorsky, A., Alain, T., Gkogkas, C., Stern-Ginossar, N., Tuschl, T., Gingras, A. C., Duchaine, T. F. & Sonenberg, N. Translational control of ERK signaling through miRNA/4EHP-directed silencing. Elife 7, doi:10.7554/eLife.35034 (2018).
2017
Martin, L. J., Smith, S. B., Khoutorsky, A., Magnussen, C. A., Samoshkin, A., Sorge, R. E., Cho, C., Yosefpour, N., Sivaselvachandran, S., Tohyama, S., Cole, T., Khuong, T. M., Mir, E., Gibson, D. G., Wieskopf, J. S., Sotocinal, S. G., Austin, J. S., Meloto, C. B., Gitt, J. H., Gkogkas, C., Sonenberg, N., Greenspan, J. D., Fillingim, R. B., Ohrbach, R., Slade, G. D., Knott, C., Dubner, R., Nackley, A. G., Ribeiro-da-Silva, A., Neely, G. G., Maixner, W., Zaykin, D. V., Mogil, J. S. & Diatchenko, L. Epiregulin and EGFR interactions are involved in pain processing. J Clin Invest 127, 3353-3366, doi:10.1172/JCI87406 (2017).
Moy, J. K., Khoutorsky, A., Asiedu, M. N., Black, B. J., Kuhn, J. L., Barragan-Iglesias, P., Megat, S., Burton, M. D., Burgos-Vega, C. C., Melemedjian, O. K., Boitano, S., Vagner, J., Gkogkas, C. G., Pancrazio, J. J., Mogil, J. S., Dussor, G., Sonenberg, N. & Price, T. J. The MNK-eIF4E Signaling Axis Contributes to Injury-Induced Nociceptive Plasticity and the Development of Chronic Pain. The Journal of neuroscience : the official journal of the Society for Neuroscience 37, 7481-7499, doi:10.1523/JNEUROSCI.0220-17.2017 (2017).
Gantois, I., Khoutorsky, A., Popic, J., Aguilar-Valles, A., Freemantle, E., Cao, R., Sharma, V., Pooters, T., Nagpal, A., Skalecka, A., Truong, V. T., Wiebe, S., Groves, I. A., Jafarnejad, S. M., Chapat, C., McCullagh, E. A., Gamache, K., Nader, K., Lacaille, J. C., Gkogkas, C. G.* & Sonenberg, N.* Metformin ameliorates core deficits in a mouse model of fragile X syndrome. Nature medicine 23, 674-677, doi:10.1038/nm.4335 (2017). *co-last author
Chapat, C., Jafarnejad, S. M., Matta-Camacho, E., Hesketh, G. G., Gelbart, I. A., Attig, J., Gkogkas, C. G., Alain, T., Stern-Ginossar, N., Fabian, M. R., Gingras, A. C., Duchaine, T. F. & Sonenberg, N. Cap-binding protein 4EHP effects translation silencing by microRNAs. Proceedings of the National Academy of Sciences of the United States of America 114, 5425-5430, doi:10.1073/pnas.1701488114 (2017).
Tuttle, A. H., Tansley, S., Dossett, K., Tohyama, S., Khoutorsky, A., Maldonado-Bouchard, S., Stein, L., Gerstein, L., Crawhall-Duk, H., Pearl, R., Sukosd, M., Leger, P., Hardt, O. M., Yachnin, D., Austin, J. S., Chan, C. M., Pooters, T., Groves, I., Martin, L. J., Sonenberg, N., Gkogkas, C. G.* & Mogil, J. S.* Social propinquity in rodents as measured by tube cooccupancy differs between inbred and outbred genotypes. Proceedings of the National Academy of Sciences of the United States of America 114, 5515-5520, doi:10.1073/pnas.1703477114 (2017). *co-last author
2016
Tahmasebi S., Jafarnejad S. M., Tam I. S., Gonatopoulos-Pournatzis T., Matta-Camacho E., Tsukumo Y., Yanagiya A., Li W., Atlasi Y., Caron M., Braunschweig U., Pearl D., Khoutorsky A., Gkogkas C. G., Nadon R., Bourque G., Yang X. J., Tian B., Stunnenberg H. G., Yamanaka Y., Blencowe B. J., Giguère V., & Sonenberg N. Control of embryonic stem cells self-renewal and differentiation via coordinated splicing and translation of YY2. PNAS doi: 10.1073/pnas.1615540113 (2016)
Khoutorsky, A., Sorge R.E., Prager-Khoutorsky M., Pawlowski S. A., Longod G., Jafarnejad S. M., Tahmasebi S., Martin L., Pitchere M. H., Gkogkas C. G., Sharif-Naeinig R., Alfredo Ribeiro-da-Silvad A., Bourque C. W., Cerveroh F., Mogil J. S., & Sonenberg N. eIF2alpha phosphorylation controls thermal nociception. PNAS doi: 10.1073/pnas.1614047113 (2016)
Skalecka, A., Liszewska, E., Bilinski, R., Gkogkas, C., Khoutorsky, A., Malik, A. R., Sonenberg, N. & Jaworski, J. mTOR kinase is needed for the development and stabilization of dendritic arbors in newly born olfactory bulb neurons. Dev Neurobiol,doi:10.1002/dneu.22392 (2016).
2015
Khoutorsky, A., Bonin, R. P., Sorge, R. E., Gkogkas, C. G., Pawlowski, S. A., Jafarnejad, S. M., Pitcher, M. H., Alain, T., Perez-Sanchez, J., Salter, E. W., Martin, L., Ribeiro-da-Silva, A., De Koninck, Y., Cervero, F., Mogil, J. S. & Sonenberg, N. Translational control of nociception via 4E-binding protein 1. Elife 4, doi:10.7554/eLife.12002 (2015).
Maity, S., Rah, S., Sonenberg, N., Gkogkas, C. G. & Nguyen, P. V. Norepinephrine triggers metaplasticity of LTP by increasing translation of specific mRNAs. Learn Mem 22, 499-508, doi:10.1101/lm.039222.115 (2015).
Aguilar-Valles, A., Matta-Camacho, E., Khoutorsky, A., Gkogkas, C., Nader, K., Lacaille, J. C. & Sonenberg, N. Inhibition of Group I Metabotropic Glutamate Receptors Reverses Autistic-Like Phenotypes Caused by Deficiency of the Translation Repressor eIF4E Binding Protein 2. The Journal of neuroscience : the official journal of the Society for Neuroscience 35, 11125-11132, doi:10.1523/JNEUROSCI.4615-14.2015 (2015).
Cao, R., Gkogkas, C. G., de Zavalia, N., Blum, I. D., Yanagiya, A., Tsukumo, Y., Xu, H., Lee, C., Storch, K. F., Liu, A. C., Amir, S. & Sonenberg, N. Light-regulated translational control of circadian behavior by eIF4E phosphorylation. Nature Neuroscience 18, 855-862, doi:10.1038/nn.4010 (2015).
Aulas, A., Caron, G., Gkogkas, C. G., Mohamed, N. V., Destroismaisons, L., Sonenberg, N., Leclerc, N., Parker, J. A. & Vande Velde, C. G3BP1 promotes stress-induced RNA granule interactions to preserve polyadenylated mRNA. J Cell Biol 209, 73-84, doi:10.1083/jcb.201408092 (2015).
2014
Gkogkas, C. G., Khoutorsky, A., Cao, R., Jafarnejad, S. M., Prager-Khoutorsky, M., Giannakas, N., Kaminari, A., Fragkouli, A., Nader, K., Price, T. J., Konicek, B. W., Graff, J. R., Tzinia, A. K., Lacaille, J. C. & Sonenberg, N. Pharmacogenetic inhibition of eIF4E-dependent Mmp9 mRNA translation reverses fragile X syndrome-like phenotypes. Cell reports 9, 1742-1755, doi:10.1016/j.celrep.2014.10.064 (2014).
Jung, H., Gkogkas, C. G., Sonenberg, N. & Holt, C. E. Remote control of gene function by local translation. Cell 157, 26-40, doi:10.1016/j.cell.2014.03.005 (2014).
Tahmasebi, S., Alain, T., Rajasekhar, V. K., Zhang, J. P., Prager-Khoutorsky, M., Khoutorsky, A., Dogan, Y., Gkogkas, C. G., Petroulakis, E., Sylvestre, A., Ghorbani, M., Assadian, S., Yamanaka, Y., Vinagolu-Baur, J. R., Teodoro, J. G., Kim, K., Yang, X. J. & Sonenberg, N. Multifaceted regulation of somatic cell reprogramming by mRNA translational control. Cell Stem Cell 14, 606-616, doi:10.1016/j.stem.2014.02.005 (2014).
2013
Gkogkas, C. G. & Sonenberg, N. Translational control and autism-like behaviors. Cell Logist 3, e24551, doi:10.4161/cl.24551 (2013).
Cao, R., Robinson, B., Xu, H., Gkogkas, C., Khoutorsky, A., Alain, T., Yanagiya, A., Nevarko, T., Liu, A. C., Amir, S. & Sonenberg, N. Translational control of entrainment and synchrony of the suprachiasmatic circadian clock by mTOR/4E-BP1 signaling. Neuron 79, 712-724, doi:10.1016/j.neuron.2013.06.026 (2013).
Khoutorsky, A., Gkogkas, C. G.*, Yanagiya, A.*, Fabian, M. R., Prager-Khoutorsky, M., Cao, R., Gamache, K., Bouthiette, F., Parsyan, A., Sorge, R. E., Mogil, J. S., Nader, K., Lacaille, J. C. & Sonenberg, N. Control of synaptic plasticity and memory via suppression of poly(A)-binding protein. Neuron 78, 298-311, doi:10.1016/j.neuron.2013.02.025 (2013).
Ran, I., Gkogkas, C. G., Vasuta, C., Tartas, M., Khoutorsky, A., Laplante, I., Parsyan, A., Nevarko, T., Sonenberg, N. & Lacaille, J. C. Selective regulation of GluA subunit synthesis and AMPA receptor-mediated synaptic function and plasticity by the translation repressor 4E-BP2 in hippocampal pyramidal cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 33, 1872-1886, doi:10.1523/JNEUROSCI.3264-12.2013 (2013).
Gkogkas, C. G., Khoutorsky, A., Ran, I., Rampakakis, E., Nevarko, T., Weatherill, D. B., Vasuta, C., Yee, S., Truitt, M., Dallaire, P., Major, F., Lasko, P., Ruggero, D., Nader, K., Lacaille, J. C. & Sonenberg, N. Autism-related deficits via dysregulated eIF4E-dependent translational control. Nature 493, 371-377, doi:10.1038/nature11628 (2013).
2003-2012
Chua, J. J., Schob, C., Rehbein, M., Gkogkas, C. G., Richter, D. & Kindler, S. Synthesis of two SAPAP3 isoforms from a single mRNA is mediated via alternative translational initiation. Sci Rep 2, 484, doi:10.1038/srep00484 (2012).
Parsyan, A., Svitkin, Y., Shahbazian, D., Gkogkas, C., Lasko, P., Merrick, W. C. & Sonenberg, N. mRNA helicases: the tacticians of translational control. Nat Rev Mol Cell Biol 12, 235-245, doi:10.1038/nrm3083 (2011).
Gkogkas, C., Wardrope, C., Hannah, M. & Skehel, P. The ALS8-associated mutant VAPB(P56S) is resistant to proteolysis in neurons. J Neurochem 117, 286-294, doi:10.1111/j.1471-4159.2011.07201.x (2011).
Gkogkas, C., Sonenberg, N. & Costa-Mattioli, M. Translational control mechanisms in long-lasting synaptic plasticity and memory. J Biol Chem 285, 31913-31917, doi:10.1074/jbc.R110.154476 (2010).
Bidinosti, M., Ran, I., Sanchez-Carbente, M. R., Martineau, Y., Gingras, A. C., Gkogkas, C., Raught, B., Bramham, C. R., Sossin, W. S., Costa-Mattioli, M., DesGroseillers, L., Lacaille, J. C. & Sonenberg, N. Postnatal deamidation of 4E-BP2 in brain enhances its association with raptor and alters kinetics of excitatory synaptic transmission. Mol Cell 37, 797-808, doi:10.1016/j.molcel.2010.02.022 (2010).
Rampakakis, E., Gkogkas, C., Di Paola, D. & Zannis-Hadjopoulos, M. Replication initiation and DNA topology: The twisted life of the origin. J Cell Biochem 110, 35-43, doi:10.1002/jcb.22557 (2010).
Gkogkas, C., Middleton, S., Kremer, A. M., Wardrope, C., Hannah, M., Gillingwater, T. H. & Skehel, P. VAPB interacts with and modulates the activity of ATF6. Hum Mol Genet 17, 1517-1526, doi:10.1093/hmg/ddn040 (2008).
Gkogkas, C. G.*, Vernikos, G. S.*, Promponas, V. J. & Hamodrakas, S. J. GeneViTo: visualizing gene-product functional and structural features in genomic datasets. BMC Bioinformatics 4, 53, doi:10.1186/1471-2105-4-53 (2003). *co-first