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Ivan Topisirovic


Ph.D. in Molecular and Cellular Biology and Biochemistry, Faculty of Biology, University of Belgrade, Serbia, 2003

M.D., School of Medicine, University of Belgrade, Serbia, 2000

Current position

Associate Member, Department of Experimental Medicine, McGill University, Canada

Investigator, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Canada

Assistant Professor, Department of Oncology McGill University, Canada


Peer reviewed journals

  1. 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 Biol 11(5): e1001564.
  2. Alain, T., Morita, M., Fonseca, B. D., Yanagiya, A., Siddiqui, N., Bhat, M., Zammit, D., Marcus, V., Metrakos, P., Voyer, L. A., Gandin, V., Liu, Y., Topisirovic, I. and Sonenberg, N. (2012). eIF4E/4E-BP ratio predicts the efficacy of mTOR targeted therapies. Cancer Res 72(24): 6468-6476.
  3. Javeshghani, S., Zakikhani, M., Austin, S., Bazile, M., Blouin, M. J., Topisirovic, I., St-Pierre, J. and Pollak, M. N. (2012). Carbon source and myc expression influence the antiproliferative actions of metformin. Cancer Res 72(23): 6257-6267.
  4. Morita, M., Ler, L. W., Fabian, M. R., Siddiqui, N., Mullin, M., Henderson, V. C., Alain, T., Fonseca, B. D., Karashchuk, G., Bennett, C. F., Kabuta, T., Higashi, S., Larsson, O., Topisirovic, I., Smith, R. J., Gingras, A. C. and Sonenberg, N. (2012). A novel 4EHP-GIGYF2 translational repressor complex is essential for mammalian development. Mol Cell Biol 32(17): 3585-3593.
  5. Larsson, O., Morita, M., Topisirovic, I., Alain, T., Blouin, M. J., Pollak, M. and Sonenberg, N. (2012). Distinct perturbation of the translatome by the antidiabetic drug metformin. Proc Natl Acad Sci U S A 109(23): 8977-8982.
  6. Herdy, B., Jaramillo, M., Svitkin, Y. V., Rosenfeld, A. B., Kobayashi, M., Walsh, D., Alain, T., Sean, P., Robichaud, N., Topisirovic, I., Furic, L., Dowling, R. J., Sylvestre, A., Rong, L., Colina, R., Costa-Mattioli, M., Fritz, J. H., Olivier, M., Brown, E., Mohr, I. and Sonenberg, N. (2012). Translational control of the activation of transcription factor NF-kappaB and production of type I interferon by phosphorylation of the translation factor eIF4E. Nat Immunol 13(6): 543-550.
  7. Topisirovic, I. and Sonenberg, N. (2011). Translational control by the eukaryotic ribosome. Cell 145(3): 333-334.
  8. Jaramillo, M., Gomez, M. A., Larsson, O., Shio, M. T., Topisirovic, I., Contreras, I., Luxenburg, R., Rosenfeld, A., Colina, R., McMaster, R. W., Olivier, M., Costa-Mattioli, M. and Sonenberg, N. (2011). Leishmania repression of host translation through mTOR cleavage is required for parasite survival and infection. Cell Host Microbe 9(4): 331-341.
  9. Deleris, P., Trost, M., Topisirovic, I., Tanguay, P. L., Borden, K. L., Thibault, P. and Meloche, S. (2011). Activation loop phosphorylation of ERK3/ERK4 by group I p21-activated kinases (PAKs) defines a novel PAK-ERK3/4-MAPK-activated protein kinase 5 signaling pathway. J Biol Chem 286(8): 6470-6478.
  10. Topisirovic, I., Svitkin, Y. V., Sonenberg, N. and Shatkin, A. J. (2011). Cap and cap-binding proteins in the control of gene expression. Wiley Interdiscip Rev RNA 2(2): 277-298.
  11. Topisirovic, I. and Sonenberg, N. (2010). 4E-BPs at the crossroads of oncogenic MAPK and AKT signaling. Pigment Cell Melanoma Res 23(5): 585-586.
  12. Dowling, R. J., Topisirovic, I., Alain, T., Bidinosti, M., Fonseca, B. D., Petroulakis, E., Wang, X., Larsson, O., Selvaraj, A., Liu, Y., Kozma, S. C., Thomas, G. and Sonenberg, N. (2010). mTORC1-mediated cell proliferation, but not cell growth, controlled by the 4E-BPs. Science 328(5982): 1172-1176.
  13. Carnevalli, L. S., Masuda, K., Frigerio, F., Le Bacquer, O., Um, S. H., Gandin, V., Topisirovic, I., Sonenberg, N., Thomas, G. and Kozma, S. C. (2010). S6K1 plays a critical role in early adipocyte differentiation. Dev Cell 18(5): 763-774.
  14. Topisirovic, I. and Sonenberg, N. (2010). Cell biology. Burn out or fade away? Science 327(5970): 1210-1211.
  15. Garcia, C. C., Topisirovic, I., Djavani, M., Borden, K. L., Damonte, E. B. and Salvato, M. S. (2010). An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein. Biochem Biophys Res Commun 393(4): 625-630.
  16. Shahbazian, D., Parsyan, A., Petroulakis, E., Topisirovic, I., Martineau, Y., Gibbs, B. F., Svitkin, Y. and Sonenberg, N. (2010). Control of cell survival and proliferation by mammalian eukaryotic initiation factor 4B. Mol Cell Biol 30(6): 1478-1485.
  17. Dowling, R. J., Topisirovic, I., Fonseca, B. D. and Sonenberg, N. (2010). Dissecting the role of mTOR: lessons from mTOR inhibitors. Biochim Biophys Acta 1804(3): 433-439.
  18. Petroulakis, E., Parsyan, A., Dowling, R. J., LeBacquer, O., Martineau, Y., Bidinosti, M., Larsson, O., Alain, T., Rong, L., Mamane, Y., Paquet, M., Furic, L., Topisirovic, I., Shahbazian, D., Livingstone, M., Costa-Mattioli, M., Teodoro, J. G. and Sonenberg, N. (2009). p53-dependent translational control of senescence and transformation via 4E-BPs. Cancer Cell 16(5): 439-446.
  19. Topisirovic, I., Gutierrez, G. J., Chen, M., Appella, E., Borden, K. L. and Ronai, Z. A. (2009). Control of p53 multimerization by Ubc13 is JNK-regulated. Proc Natl Acad Sci U S A 106(31): 12676-12681.
  20. Ploski, J. E., Topisirovic, I., Park, K. W., Borden, K. L. and Radu, A. (2009). A mechanism of nucleocytoplasmic trafficking for the homeodomain protein PRH. Mol Cell Biochem 332(1-2): 173-181.
  21. Topisirovic, I., Siddiqui, N. and Borden, K. L. (2009). The eukaryotic translation initiation factor 4E (eIF4E) and HuR RNA operons collaboratively regulate the expression of survival and proliferative genes. Cell Cycle 8(7): 960-961.
  22. Topisirovic, I., Siddiqui, N., Lapointe, V. L., Trost, M., Thibault, P., Bangeranye, C., Pinol-Roma, S. and Borden, K. L. (2009). Molecular dissection of the eukaryotic initiation factor 4E (eIF4E) export-competent RNP. EMBO J 28(8): 1087-1098.
  23. Topisirovic, I., Siddiqui, N., Orolicki, S., Skrabanek, L. A., Tremblay, M., Hoang, T. and Borden, K. L. (2009). Stability of eukaryotic translation initiation factor 4E mRNA is regulated by HuR, and this activity is dysregulated in cancer. Mol Cell Biol 29(5): 1152-1162.
  24. Culjkovic, B., Topisirovic, I. and Borden, K. L. (2007). Controlling gene expression through RNA regulons: the role of the eukaryotic translation initiation factor eIF4E. Cell Cycle 6(1): 65-69.
  25. Culjkovic, B., Topisirovic, I., Skrabanek, L., Ruiz-Gutierrez, M. and Borden, K. L. (2006). eIF4E is a central node of an RNA regulon that governs cellular proliferation. J Cell Biol 175(3): 415-426.
  26. Volpon, L., Osborne, M. J., Topisirovic, I., Siddiqui, N. and Borden, K. L. (2006). Cap-free structure of eIF4E suggests a basis for conformational regulation by its ligands. EMBO J 25(21): 5138-5149.
  27. Laine, A., Topisirovic, I., Zhai, D., Reed, J. C., Borden, K. L. and Ronai, Z. (2006). Regulation of p53 localization and activity by Ubc13. Mol Cell Biol 26(23): 8901-8913.
  28. Garcia, C. C., Djavani, M., Topisirovic, I., Borden, K. L., Salvato, M. S. and Damonte, E. B. (2006). Arenavirus Z protein as an antiviral target: virus inactivation and protein oligomerization by zinc finger-reactive compounds. J Gen Virol 87(Pt 5): 1217-1228.
  29. Kentsis, A., Volpon, L., Topisirovic, I., Soll, C. E., Culjkovic, B., Shao, L. and Borden, K. L. (2005). Further evidence that ribavirin interacts with eIF4E. RNA 11(12): 1762-1766.
  30. Topisirovic, I. and Borden, K. L. (2005). Homeodomain proteins and eukaryotic translation initiation factor 4E (eIF4E): an unexpected relationship. Histol Histopathol 20(4): 1275-1284.
  31. Dragasevic, N. T., Culjkovic, B., Klein, C., Ristic, A., Keckarevic, M., Topisirovic, I., Vukosavic, S., Svetel, M., Kock, N., Stefanova, E., Romac, S. and Kostic, V. S. (2006). Frequency analysis and clinical characterization of different types of spinocerebellar ataxia in Serbian patients. Mov Disord 21(2): 187-191.
  32. Culjkovic, B., Topisirovic, I., Skrabanek, L., Ruiz-Gutierrez, M. and Borden, K. L. (2005). eIF4E promotes nuclear export of cyclin D1 mRNAs via an element in the 3'UTR. J Cell Biol 169(2): 245-256.
  33. Djavani, M., Topisirovic, I., Zapata, J. C., Sadowska, M., Yang, Y., Rodas, J., Lukashevich, I. S., Bogue, C. W., Pauza, C. D., Borden, K. L. and Salvato, M. S. (2005). The proline-rich homeodomain (PRH/HEX) protein is down-regulated in liver during infection with lymphocytic choriomeningitis virus. J Virol 79(4): 2461-2473.
  34. Topisirovic, I., Kentsis, A., Perez, J. M., Guzman, M. L., Jordan, C. T. and Borden, K. L. (2005). Eukaryotic translation initiation factor 4E activity is modulated by HOXA9 at multiple levels. Mol Cell Biol 25(3): 1100-1112.
  35. Kentsis, A., Topisirovic, I., Culjkovic, B., Shao, L. and Borden, K. L. (2004). Ribavirin suppresses eIF4E-mediated oncogenic transformation by physical mimicry of the 7-methyl guanosine mRNA cap. Proc Natl Acad Sci U S A 101(52): 18105-18110.
  36. Topisirovic, I., Ruiz-Gutierrez, M. and Borden, K. L. (2004). Phosphorylation of the eukaryotic translation initiation factor eIF4E contributes to its transformation and mRNA transport activities. Cancer Res 64(23): 8639-8642.
  37. Topisirovic, I., Guzman, M. L., McConnell, M. J., Licht, J. D., Culjkovic, B., Neering, S. J., Jordan, C. T. and Borden, K. L. (2003). Aberrant eukaryotic translation initiation factor 4E-dependent mRNA transport impedes hematopoietic differentiation and contributes to leukemogenesis. Mol Cell Biol 23(24): 8992-9002.
  38. Topisirovic, I., Culjkovic, B., Cohen, N., Perez, J. M., Skrabanek, L. and Borden, K. L. (2003). The proline-rich homeodomain protein, PRH, is a tissue-specific inhibitor of eIF4E-dependent cyclin D1 mRNA transport and growth. EMBO J 22(3): 689-703.
  39. Topisirovic, I., Dragasevic, N., Savic, D., Ristic, A., Keckarevic, M., Keckarevic, D., Culjkovic, B., Petrovic, I., Romac, S. and Kostic, V. S. (2002). Genetic and clinical analysis of spinocerebellar ataxia type 8 repeat expansion in Yugoslavia. Clin Genet 62(4): 321-324.
  40. Topisirovic, I., Capili, A. D. and Borden, K. L. (2002). Gamma interferon and cadmium treatments modulate eukaryotic initiation factor 4E-dependent mRNA transport of cyclin D1 in a PML-dependent manner. Mol Cell Biol 22(17): 6183-6198.
  41. Savic, D., Topisirovic, I., Keckarevic, M., Keckarevic, D., Major, T., Culjkovic, B., Stojkovic, O., Rakocevic-Stojanovic, V., Mladenovic, J., Todorovic, S., Apostolski, S. and Romac, S. (2001). Is the 31 CAG repeat allele of the spinocerebellar ataxia 1 (SCA1) gene locus non-specifically associated with trinucleotide expansion diseases? Psychiatr Genet 11(4): 201-205.
  42. Romac, S., Culjkovic, B., Vukosavic, S., Stojkovic, O., Savic, D., Keckarevic, D., Zamurovic, N., Major, T., Keckarevic, M., Topisirovic, I. (2001). Dynamic mutations as a cause of hereditary neurological and psychiatric diseases. ”JUGOSLOVENSKA MEDICINSKA BIOHEMIJA-YUGOSLAV MEDICAL BIOCHEMISTRY 20 (1): 1-7.

Book Chapters

  1. Furic, L., Livingstone, M., Topisirovic, I. and Sonenberg, N. (2011). Actions of Insulin As a Survival and Growth Factor: Akt, mTOR, and Regulation of Translation. in Insulin Resistance and Cancer, 1st edition; Fantus, I. George (Ed.),Springer: 181-192, ISBN 978-1-4419-9910-8.
  2. Topisirovic, I. and Sonenberg, N. (2011). mRNA translation and energy metabolism in cancer: the role of the MAPK and mTORC1 pathways. Cold Spring Harbor Symposia on Quantitative Biology, 76:355-67. doi: 10.1101/sqb.2011.76.010785, Cold Spring Harbor Laboratory Press.
  3. Roux, P. P. and Topisirovic, I. (2012). Regulation of mRNA Translation by Signaling Pathways. In “Translational Control in Biology and Medicine”, Cold Spring Harbor Perspectives in Biology 4(11) , doi:pii: a012252. 10.1101/cshperspect.a012252.
Protocols by Ivan Topisirovic
  1. Polysome Profiling Analysis