Ivan Topisirovic obtained his M.D. and Ph.D. from the University of Belgrade, Serbia. He completed his post-doctoral training, first with Dr. Katherine L.B. Borden (Mount Sinai School of Medicine, New York and IRIC, Université de Montréal), then with Dr. Nahum Sonenberg (McGill University). During his post-doctoral tenure, he was studying how gene expression is regulated at the post-transcriptional level. In particular, he focused on the post-transcriptional regulatory networks centered on the eukaryotic translation initiation factor 4E (eIF4E), which is a pivotal regulator of mRNA translation and whose activity is frequently dysregulated in cancer. In 2011, he joined the Lady Davis Institute as an independent investigator and obtained an Assistant Professor position in the Department of Oncology, McGill University.
Major Research Activities
His laboratory is interested in studying the molecular mechanisms which underlie the role of mRNA translation in modulating growth (increase in cell volume) and proliferation (increase in cell number) of normal and malignantly transformed cells. Rates of cell growth and proliferation are modulated by signaling pathways in response to various extracellular stimuli and intracellular cues. The mammalian target of rapamycin (mTOR) pathway is a major regulator of mRNA translation, cell growth and proliferation, and it is frequently dysregulated in human diseases such as cancer, diabetes and heart disease. The main focus of his future studies will be to determine how the effects of mTOR on mRNA translation influence cell growth and proliferation.
Changes in growth and proliferation rates are also characterized by alterations in gene expression. To achieve optimal growth and proliferation rates in a given environment, cells need to coordinate the expression of a subset of genes which need to be expressed at specific time points. He aims to elucidate post-transcriptional regulatory networks which play a role in coordinating the expression of genes which regulate cell growth and proliferation and investigate the mechanisms which lead to aberrant function of these networks in human disease.
Dowling RJ*, Topisirovic I*, Alain T, Bidinosti M, Fonseca BD, Petroulakis E, Wang X, Larsson O, Selvaraj A, Liu Y, Morrow T, Kozma SC, Thomas G and Sonenberg N. (2010) mTORC1-mediated cell proliferation, but not cell growth, is controlled by the 4E-BPs. Science 328(5982):1172-6 (*equally contributing first author).
Topisirovic I, Gutierrez GJ, Chen M, Appella E, Borden KL, Ronai ZA. (2009) Control of p53 multimerization by Ubc13 is JNK-regulated. Proc Natl Acad Sci U S A. 106(31):1 2676-81.
Topisirovic I., Siddiqui N., Leroux Lapointe V., Trost M., Thibault P., Bangeranye C., Piñol-Roma S., Borden K.L.B. (2009) Molecular dissection of the eukaryotic initiation factor 4E (eIF4E) export competent RNP. EMBO J. 2009 28(8):1087-98.