Dr. Tommy Alain

Biography

Research

Dr. Tommy Alain is a Scientist at the Children’s Hospital of Eastern Ontario (CHEO) Research Institute and Associate Professor in the Department of Biochemistry, Microbiology and Immunology at the University of Ottawa. His training is in virology, innate immune responses, cell biology, and oncology. Dr. Alain received his B.Sc. (2000) in Biochemistry from Université Laval in Québec City and his Ph.D. (2007) in Medical Science from the University of Calgary. During his Ph.D., Dr. Alain studied the virology and the oncolytic potencies of reovirus, vesicular stomatitis virus, herpes simplex virus and myxoma virus against brain cancers. He then pursued post-doctoral work at McGill University studying mRNA translational control and the mammalian target of rapamycin (mTOR) signaling pathway, linking both viral immunity and oncology research. Dr. Alain’s current research at the CHEO Research Institute and the University of Ottawa focuses on exploiting translation initiation factors and downstream effectors of mTOR complex 1 (mTORC1) to modulate innate immune responses to pathogens, and to augment the anti-proliferative efficacies of cancer therapeutics.

Selected Publications

• Hoang HD, Graber TE, Jia JJ, Vaidya N, Gilchrist VH, Xiang X, Li W, Cowan KN, Gkogkas CG, Jaramillo M, Jafarnejad M, Alain T. Induction of an alternative 5’ leader enhances translation of the ciliopathy gene Inpp5e and resistance to oncolytic virus infection. Cell Reports 2019 Dec 17;29(12):4010-4023. 
• Zakaria C, Sean P, Hoang HD, Leroux LP, Watson M, Workenhe ST, Hearnden J, Pearl D, Truong TV, Robichaud N, Yanagiya A, Tahmasebi S, Jafarnejad SM, Jia JJ, Graber TE, Pelin A, Diallo JS, Le Boeuf F, Bell JC, Mossman K, Jaramillo M, Sonenberg N, Alain T. Active-site mTOR inhibitors augment HSV1 infection of cancer cells with elevated eIF4E activity. PLOS Pathog. 2018 Aug 23;14(8):e1007264.
• Hoang HD, Graber TE, Alain T. Battling for ribosomes: Translational control at the forefront of the antiviral response. J Mol Biol.2018 Jul 6;430(14):1965-1992.
• Tsukumo Y, Sonenberg N, Alain T. Transcriptional induction of 4E-BP3 prolongs translation repression. Cell Cycle 2016 Aug 26:1-2.
• Bhat M, Morita M, Zammit D, Razumilava N, Bronk S, Zhao Y, Zakaria C, Metrakos P, Pollak M, Gores G, Sonenberg N, Jaramillo M, Alain T. Metformin requires 4E-BPs to induce apoptosis and repress translation of Mcl-1 in hepatocellular carcinoma cells. Oncotarget 2016 Jul 18. doi: 10.18632/oncotarget.10671.
• Tsukumo Y, Alain T, Fonseca BD, Nadon R, Sonenberg N. Translation control during prolonged mTORC1 inhibition mediated by 4E-BP3. Nat Commun 2016 Jun 20;7:11776.
• Wang F, Alain T, Szretter KJ, Pol J, Hoang HD, Fonseca BD, Zakaria C, Hesch A, Yan Chan ES, Tuinman C, Suthar MS, Jiang Z, Thomas G, Kozma SC, Gale M, Fitzgerald KA, Diamond MS, Mossman K, Sonenberg N, Wan Y, Lichty BD. S6K-STING interaction regulates cytosolic DNA-mediated activation of the transcription factor IRF3. Nat Immunol 2016 May;17(5):514-22.
• Fonseca BD, Zakaria C, Jia JJ, Graber TE, Svitkin Y, Tahmasebi S, Healy D, Hoang HD, Jensen JM, Diao IT, Lussier A, Dajadian C, Padmanabhan N, Wang W, Matta-Camacho E, Hearnden J, Smith EM, Tsukumo Y, Yanagiya A, Morita M, Petroulakis E, Gonzalez JL, Hernandez G, Alain T, Damgaard CK.  La-related Protein 1 (LARP1) represses terminal oligopyrimidine (TOP) mRNA translation downstream of mTOR Complex 1 (mTORC1). J Biol Chem 2015 Jun 26;290(26):15996-6020.
• Nehdi A, Sean P, Linares I, Colina R, Jaramillo M, Alain T. Deficiency in either 4E-BP1 or 4E-BP2 augments the innate anti-viral immune response. PLoS One 2014 Dec 22;9(12):e114854.
• Tahmasebi S, Alain T, Rajasekhar VK, Zhang JP, Khoutorsky MP, Khoutorsky A, Dogan Y, Gkogkas CG, Petroulakis E, Sylvestre A, Ghorbani M, Assadian S, Yamanaka Y, Teodoro JG, Vinagolu Baur JR, Kim K, Yang XJ, Sonenberg N. eIF4E-binding protein-dependent translational control of somatic cell reprogramming. Cell Stem Cell 2014 May 1;14(5):606-16.
• Alain T, Morita M, Fonseca BD, Yanagiya A, Siddiqui N, Bhat M, Zammit D, Markus V, Metrakos P, Voyer LA, Gandin V, Liu Y, Topisirovic I, Sonenberg N. eIF4E/4E-BP ratio predicts the efficacy of mTOR targeted therapies. Cancer Res. 2012 Dec 15;72(24):6468-6476. 
• Alain T, Lun XQ, Martineau Y, Sean P, Pulendran B, Petroulakis E, Zemp FJ, Lemay C, Roy D, Forsyth PA, Costa-Mattioli M, Sonenberg N. Vesicular stomatitis virus oncolysis is potentiated by mTORC1-dependent inhibition of type-I IFN production. PNAS. 2010 Jan 26;107(4):1576-81.
•  Alain T, Kim TSY, Lun XQ, Liacini A, Schiff LA, Senger DL, Forsyth PA. Proteolytic disassembly is a critical determinant for reovirus oncolysis. Mol Ther. 2007 Aug;15(8):1512-21.
• Alain T, Kim M, Johnston RN, Urbanski SJ, Kossakowska AE, Forsyth PA, Lee PW. The oncolytic effect in vivo of reovirus on tumor cells that have survived reovirus cell killing in vitro. Br J Cancer. 2006 Oct 23;95(8):1020-7.
• Alain T, Hirasawa K, Pon KJ, Nishikawa SG, Urbanski SJ, Auer Y, Luider J, Martin A, Johnston RN, Janowska-Wieczorek A, Lee PWK, Kossakowska AE. Reovirus therapy of lymphoid malignancies. Blood. 2002 Dec 1; 100(12) 4146-53.