Arkady Khoutorsky
William Dawson Scholar
My current research program is focused on three major themes: (I) investigation of mechanisms by which dysregulation of translational control contributes to the development of chronic pain, (II) studying the role of extracellular matrix (ECM) and matrix metalloproteinases (MMPs) in the regulation of spinal cord plasticity and the development of chronic pain, and (III) examining the mechanisms by which dysregulation of integrated stress response (ISR) pathway contributes to the pathophysiology of Fragile X syndrome
- Dysregulation of translational control and the development of chronic pain
- Extracellular matrix (ECM) and matrix metalloproteinases (MMPs) in the regulation of spinal cord plasticity
- Dysregulation of integrated stress response (ISR) pathway and pathophysiology of Fragile X syndrome
Peer-reviewed Journal Articles
Uttam, S.*, Wong, C.*, Tansley, S*., Prager-Khoutorsky, M., Mogil, J., Gkogkas, CG., and Khoutorsky, A. (2018). Translational profiling of dorsal root ganglia and spinal cord in a mouse model of neuropathic pain. Neurobiology of Pain, https://doi.org/10.1016/j.ynpai.2018.04.001.
Jafarnejad, M., Chapat, C., Matta-Camacho, E., Gelbart, IA., Hesketh, JG., Arguello, M., Shapiro, AM., Khoutorsky, A., Alain, T., Gkogkas, CG., Stern-Ginossar, N., Gingras, AC., Duchaine, T., and Sonenberg, N. (2018) Translational control of ERK signalling pathway by the mRNA cap-binding protein 4EHP. eLife, doi: 10.7554/eLife.35034.
Moy, JK., Khoutorsky, A., Asiedu, MN., Dussor, G., and Price, TJ. (2018) eIF4E phosphorylation influences Bdnf mRNA translation in mouse dorsal root ganglion neurons. Frontiers in Cellular Neuroscience, doi: 10.3389/fncel.2018.00029.
Moy, JK., Khoutorsky, A., Asiedu, MN., Burgos-Vega, CC., Megat, S., Melemedjian, OK., Boitano, S., Vagner, J., Gkogkas, CG., Mogil, JS., Dussor, G., Sonenberg, N., and Price, TJ. (2017) The MNK-eIF4E Signaling Axis Contributes to Injury-Induced Nociceptive Plasticity and the Development of Chronic Pain. J. Neuroscience, Jul 3. pii: 0220-17.
Martin, L., Smith, S., Khoutorsky, A., Magnussen, C., Sorge, R., Mir, E., Gibson, D., Otis, V., Wieskopf, J., Sotocinal, S., Austin, JS., Salter, M., Gkogkas, CG, Sonenberg, N., Gendron, L., Greenspan, J., Fillingim, R., Ohrbach, R., Slade, G., Knott, C., Dubner, R., Ribeiro-da-Silva, A., Maixner, W., Zaykin, D., Mogil, JS and Diatchenko, L. (2017). Epiregulin and epidermal growth factor receptor involvement in pain revealed by a reverse translational approach. Journal of Clinical Investigation, Aug 7. pii: 87406. doi: 10.1172/JCI87406.
Gantois, I.§, Khoutorsky, A.§, Popic, J.§, Freemantle, E., Aguilar-Valles, A., Cao, R., Sharma. V., Nagpal, A., Gamache, K., Chapat, C., Pooters., Nader, K., Lacaille, JC., Gkogkas, CG, Sonenberg, N. (2017). Metformin ameliorates core deficits in a mouse model of fragile X syndrome. Nature Medicine, Jun 23(6):674-677. (§ equal contribution).
Tuttle, AH., Dossett, K., Tohyama, S., Khoutorsky, A., Stein, L., Gerstein, L., Pearl, R., Sukosd, M., Leger, P., Yachnin, D., Austin, JS., Sonenberg, N., Gkogkas, C., and Mogil, JS. (2017). Social propinquity in rodents as measured by tube co-occupancy. PNAS, 114(21): 5515-5520.
Khoutorsky, A.§, Sorge, R.§, Prager-Khoutorsky, M.§, Gkogkas, C., Martin, L., Pitcher, M., Austin, JS., Pawlowski, SA., Longo, G., Sharif-Naeini, R., Ribeiro-da-Silva, A., Bourque, CW., Cervero, F., Mogil, J., and Sonenberg, N. (2016). eIF2alpha phosphorylation controls thermal nociception. PNAS, 113(42):11949-11954, (§ equal contribution).
Tahmasebi, S., Jafarnejad, SM., Tam, IS., Gonatopoulos-Pournatzis, T., Matta-Camacho, E., Tsukumo, Y., Yanagiya, A., Li, W., Atlasi, Y., Caron, M., Braunschweig, U., Pearl, D., Khoutorsky, A., Gkogkas, CG., Nadon, R., Bourque, G., Yang, XJ., Tian, B., Stunnenberg, HG., Yamanaka, Y., Blencowe, BJ., Giguère, V. and Sonenberg, N. (2016). Control of embryonic stem cell self-renewal and differentiation via coordinated alternative splicing and translation of YY2. PNAS, 113(44):12360-12367.
Skałecka, A., Bilinski, R., Liszewska, E., Gkogkas, C., Khoutorsky, A., Sonenberg, N., and Jaworski, J. (2016). 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.
Khoutorsky, A.§, Bonin, RP.§, Sorge, RE.§, Gkogkas, G., Jafarnejad, SM., Pitcher, MH., Alain, T., Perez-Sanchez, J., Martin, L., De Koninck, Y., Cervero, F., Mogil, JS, and Sonenberg, N. (2015). Translational control of nociception via 4E-binding protein 1. eLife, Dec 18;4. pii: e12002. (§ equal contribution).
Aguilar-Valles, A., Matta-Camacho, E., Khoutorsky, A., Gkogkas, C., Nader, K., Lacaille, JC, and Sonenberg, N. (2015). Inhibition of group I metabotropic glutamate receptors reverses autistic-like phenotypes caused by exacerbated mRNA translation. The Journal of Neuroscience, 35(31):11125-32.
Tenkerian, C., Krishnamoorthy, J., Mounir, Z., Kazimierczak, U., Khoutorsky, A., Staschke, KA., Kristof, AS., Wang, S., Hatzoglou, M., and Koromilas AE. (2015). mTORC2 balances Akt activation and eIF2alpha serine 51 phosphorylation to promote survival under stress. Mol Cancer Res, PMID: 26130148.
Gkogkas, C.§, Khoutorsky, A.§, Cao, R., Giannakas, N., Kaminari, A., Aguilar-Vales, A., Nader, K., Konicek, B., Graff, G., Tzinia, A., Lacaille, JC, and Sonenberg, N. (2014). Pharmaco-genetic inhibition of eIF4E phosphorylation reverses FXS-like phenotypes. Cell Reports, Dec 11;9(5):1742-55. (§ equal contribution).
Prager-Khoutorsky, M., Khoutorsky, A., and Bourque, CW. (2014). Microtubules regulate mechanical activation of TRPV1 in osmosensitive neurons. Neuron, Volume 83, 866–878.
Tahmasebi S, Alain T, Rajasekhar VK, Zhang JP, Prager-Khoutorsky M, Khoutorsky A, Dogan Y, Gkogkas CG, Petroulakis E, Sylvestre A, Ghorbani M, Assadian S, Yamanaka Y, Vinagolu-Baur JR, Teodoro JG, Kim K, Yang XJ, Sonenberg N. (2014). Multifaceted Regulation of Somatic Cell Reprogramming by mRNA Translational Control. Cell Stem Cell, 14(5):606-16.
Khoutorsky, A., Yanagiya, A., Gkogkas, C., Fabian, M., Prager-Khoutorsky, M., Cao, R., Gamache, K., Bouthiette, F., Parsyan, A., Sorge, R, Mogil, J, Nader, K., Lacaille, JC and Sonenberg, N. (2013). Control of synaptic plasticity and memory via suppression of poly(A)-binding protein. Neuron, Volume 78, 298–311.
Melemedjian, O.K.§, Khoutorsky, A.§, Sorge, R.E.§, Yan, J., Asiedu, M.N., Valdez, A., Ghosh, S., Dussor, G., Mogil, J.S., Sonenberg, N., et al. (2013). mTORC1 inhibition induces pain via IRS-1-dependent feedback activation of ERK. Pain 154, 1080-1091. (§ equal contribution).
Graber, T., Hebert-Seropian, S., Khoutorsky, A., David, A., Yewdell, J., Lacaille, JC., and Sossin, W. (2013). Reactivation of stalled polyribosomes mediates synaptic plasticity. PNAS, 110(40):16205-10.
Cao, R., Robinson, B, Xu, H., Gkogkas, C., Khoutorsky, A., Alain, T., Yanagiy, A., Nevarko, T., Liu A., Amir, S., and Sonenberg., N. (2013). Translational control of mammalian circadian synchrony by 4E-BP1. Neuron, Volume 79, 712–724.
Sidrauski, C., Acosta-Alvear, D., Khoutorsky, A., Vedantham, P., Hearn, B.R., Li, H., Gamache, K., Gallagher, C.M., Ang, K.K., Wilson, C., et al. (2013). Pharmacological brake-release of mRNA translation enhances cognitive memory. eLife 2, e00498.
Svitkin, Y.V., Yanagiya, A., Karetnikov, A.E., Alain, T., Fabian, M.R., Khoutorsky, A., Perreault, S., Topisirovic, I., and Sonenberg, N. (2013). Control of Translation and miRNA-Dependent Repression by a Novel Poly(A) Binding Protein, hnRNP-Q. PLoS Biology 11, e1001564.
Chaveroux, C., Eichner, L.J., Dufour, C.R., Shatnawi, A., Khoutorsky, A., Bourque, G., Sonenberg, N., and Giguere, V. (2013). Molecular and Genetic Crosstalks between mTOR and ERRalpha Are Key Determinants of Rapamycin-Induced Nonalcoholic Fatty Liver. Cell Metabolism 17, 586-598.
Gkogkas, C.G., Khoutorsky, A., Ran, I., Rampakakis, E., Nevarko, T., Weatherill, D.B., Vasuta, C., Yee, S., Truitt, M., Dallaire, P., et al. (2013). Autism-related deficits via dysregulated eIF4E-dependent translational control. Nature 493, 371-377.
Ran, I., Gkogkas, C.G., Vasuta, C., Tartas, M., Khoutorsky, A., Laplante, I., Parsyan, A., Nevarko, T., Sonenberg, N., and Lacaille, J.C. (2013). 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 33, 1872-1886.
Sorge, R.E., Lacroix-Fralish, M.L., Tuttle, A.H., Khoutorsky, A., Sotocinal, S.G., Austin, J.S., Melmed, K., Labialle, S., Schmidt, J.V., Wood, J.N., et al. (2013). The Yin and Yang of pain: variability in formalin test nociception and morphine analgesia produced by the Yin Yang 1 transcription factor gene. Genes, brain, and behavior.
Melemedjian, O.K., Asiedu, M.N., Tillu, D.V., Sanoja, R., Yan, J., Lark, A., Khoutorsky, A., Johnson, J., Peebles, K.A., Lepow, T., et al. (2011). Targeting adenosine monophosphate-activated protein kinase (AMPK) in preclinical models reveals a potential mechanism for the treatment of neuropathic pain. Molecular Pain 7, 70.
Khoutorsky, A., Heyman, A., Shoseyov, O., and Spira, M.E. (2011). Formation of hydrophilic nanochannels in the membrane of living cells by the ringlike stable protein-SP1. Nano letters 11, 2901-2904.
Khoutorsky, A., and Spira, M.E. (2009). Activity-dependent calpain activation plays a critical role in synaptic facilitation and post-tetanic potentiation. Learning and Memory 16, 129-141.
Khoutorsky, A., and Bruchim, Y. (2008). Transient leucopenia, thrombocytopenia and anaemia associated with severe acute phenobarbital intoxication in a dog. The Journal of small animal practice 49, 367-369.
Khoutorsky, A., and Spira, M.E. (2008). Calpain inhibitors alter the excitable membrane properties of cultured Aplysia neurons. Journal of Neurophysiology 100, 2784-2793.
Sahly, I.§, Khoutorsky, A.,§, Erez, H., Prager-Khoutorsky, M., and Spira, M.E. (2006). On-line confocal imaging of the events leading to structural dedifferentiation of an axonal segment into a growth cone after axotomy. The Journal of Comparative Neurology 494, 705-720. (§ equal contribution).
Khoutorsky, A., and Spira, M.E. (2005). Calcium-activated proteases are critical for refilling depleted vesicle stores in cultured sensory-motor synapses of Aplysia. Learning and Memory 12, 414-422.
Sahly, I., Erez, H., Khoutorsky, A., Shapira, E., and Spira, M.E. (2003). Effective expression of the green fluorescent fusion proteins in cultured Aplysia neurons. Journal of Neuroscience Methods 126, 111-117.
- Reviews, book chapters, books.
Uttam, S.*, Wong, C*., Price, T., and Khoutorsky, A. eIF4E-dependent Translational Control: A Central Mechanism for Regulation of Pain Plasticity, (Under review in Frontiers in Genetics), * - student under my supervision.
Gantois, I., Popic, J., Khoutorsky, A., and Sonenberg, N. Metformin for treatment of Fragile X syndrome and other neurological diseases. (Under review in Annual Reviews of Medicine).
Tahmasebi, S., Khoutorsky, A., Mathews, MB., and Sonenberg, N. (2018). Translation deregulation in human disease. Nature Review Molecular Cell Biology, doi: 10.1038/s41580-018-0034-x.
Khoutorsky, A., and Price, TJ. (2017). Translational control mechanisms in persistent pain. Trends in Neuroscience. doi: 10.1016/j.tins.2017.11.006.
Tansley, S.*, Wong, C.*, Uttam, S.*, Mogil, J., and Khoutorsky, A. (2018). Translation regulation in the spinal dorsal horn - a key mechanism for development of chronic pain. Neurobiology of Pain (In Press, https://doi.org/10.1016/j.ynpai.2018.03.003). * - under my supervision
Melemedjian, O., and Khoutorsky, A. (2015). Translation Control of Chronic Pain. Molecular and Cell Biology of Pain. Elsevier (Prog Mol Biol Transl Sci. 2015; 131:185-213).
Gkogkas, C., Aguilar-Valles, A., Khoutorsky, A., and Sonenberg, N. (2014). Translational control of autism and Fragile-X syndrome. Frontiers in Autism Research, Diagnosis, and Treatment (In Press).
Khoutorsky A., Gkogkas, C., and Sonenberg N. (2013). Translational Control of Synaptic Plasticity and Memory. In, Biophysics for the Life Sciences Vol I, 2013: Biophysical approaches to translational control of gene expression. Springer, XII, Pages 289-310.