Professor- Assistant research
Affiliation
Université de Montréal
Research Axes
Contact information
Team
- Tian Guan
- Zaynab Nouhi
With a PhD in Biochemistry and Molecular Biology, Laura Hulea heads the Regulation of Cell Metabolism and RNA Translation Research Unit. She is an assistant professor and researcher in the Faculty of Medicine and in medical specialties at Université de Montréal.
Her laboratory works on the cellular and molecular mechanisms that facilitate cellular adaptation to stress (metabolic stress, stress from the cellular environment, or stress induced by anti-cancer therapies) during normal functioning (immune response) or in pathologies (cancer, age-related diseases, etc.). The goal is to identify vulnerabilities for therapeutic purposes, such as anti-cancer treatments.
Research Unit
Regulation of Cell Metabolism and RNA Translation
Our research unit is interested in the molecular mechanisms that coordinate cellular metabolism and gene expression (specifically RNA translation) in cellular homeostasis. We also study the deregulation of these mechanisms in human pathologies such as cancer.
Goal
Our main goal is to use our unique experience in characterizing the coordination between cell signalling, gene expression and cell metabolism to identify novel molecular bases that could lead to improved anti-cancer treatments.
We use a combination of systems biology techniques (transcriptome, translatome, and metabolome analysis), classical molecular and cellular biology techniques, as well as specific and advanced RNA metabolism and translation techniques (polysome fractionation, cellular metabolite analysis using GC/MS or LC/MS, cellular bioenergetics analysis using Seahorse technology, etc.). Our group uses cellular and mouse models (cell-line derived xenografts and primary patient-derived xenografts or PDX) and is supported by advanced platforms (flow cytometry; metabolic – GC-MS, Seahorse XFe; microscopy).
Research interests
- Understand the molecular mechanisms (translational and metabolic) that help cancer cells adapt to targeted therapies (oncogenic kinase inhibitors such as HER2, BCR-ABL and BRAF) to improve anticancer treatments in the case of therapy resistance.
- Elucidate the molecular mechanisms of translational control that are regulated by the mTORC1/4E-BP/eIF4F axis to understand how to affect them using eIF4F disrupting agents.
- Use molecules with a clinical potential to exploit the vulnerabilities of cancer cells and characterize the effect of these molecules on the coordination of gene signalling, metabolism and expression.
Publications
Voir toutes les publications-
mTOR as a central regulator of lifespan and aging. Papadopoli D*, Boulay K*, Mallette F, Pollak M, Topisirovic I**, Hulea L**. F1000Research 2019, 8(F1000 Faculty Rev):998. (* equally contributing; **co-corresponding)
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Translational and HIF1alpha-dependent metabolic reprograming underpin oncometabolome plasticity and synergy between oncogenic kinase inhibitors and biguanides. Hulea L*, Gravel S-P*, Morita M*, Cargnello M, Uchenunu O, Im YK, Zhao Y, Mclaughan S, Larsson O, Ohh M, Ferreira T, Greenwood C, Bridon G, Avizonis D, Ursini-Siegel J, St-Pierre J, Pollak M**, Topisirovic I**. Cell Metab. (2018). Dec 4;28(6):817-832.e8. (* equally contributing; **co-corresponding).
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Oncogenic kinases and perturbations in protein synthesis machinery and energetics in neoplasia. Uchenunu O, Pollak M, Topisirovic I, Hulea L. J Mol Endocrinol. (2019) Feb 1;62(2):R83-R103.
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METTL13 methylation of eEF1A increases translational output to promote tumorigenesis. Liu S*, Hausmann S*, Carlson S, Fuentes ME, Francis JW, Pillai R, Lofgren SM, Hulea L, Tandoc K, Lu J, Li A, Nguyen ND, Caporicci M, Kim MP, Maitra A, Wang H, Wistuba II, Porco JA, Bassik MC, Elias JE, Song J, Topisirovic I, Van Rechem C, Mazur PM** and Gozani O**. Cell 176, 1–14 (2019), (* equally contributing; **co-corresponding).
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mTOR Controls Mitochondrial Dynamics and Cell Survival via MTFP1. Morita M, Prudent J, Basu K, Goyon V, Katsumura S, Hulea L, Pearl D, Siddiqui N, Strack S, McGuirk S, St-Pierre J, Larsson O, Topisirovic I, Vali H, McBride HM, Bergeron JJ, Sonenberg N. Mol Cell. (2017) Sep 21;67(6):922-935
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nanoCAGE reveals 5’ UTR features that define specific modes of translation of functionally related mTOR-sensitive mRNAs. Gandin V*, Masvidal L*, Hulea L*, Gravel S-P, Cargnello M, McLaughlan S, Cai Y, Balanathan P, Morita M, Rajakumar A, Furic L, Pollak M, Porco, JR Jr., St-Pierre J, Pelletier J, Larsson O**, Topisirovic I** (* equally contributing; **co-corresponding). Genome Res. (2016) May;26(5):636-48.
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The oncometabolite 2-hydroxyglutarate activates the mTOR signaling pathway. Carbonneau M, Germain MA*, Gagné LM*, Lalonde ME*, Motorina A, Guiot MC, Secco B, Vincent EE, Tumber A, Hulea L, Oppermann U, Jones RG, Laplante M, Topisirovic I, Petrecca K, Huot ME**, Mallette FA** (* equally contributing; **co-corresponding). Nat Commun. (2016) Sep 14;7:12700.
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SBI-0640756 Attenuates the Growth of Clinically Unresponsive Melanomas by Disrupting the eIF4F Translation Initiation Complex. Feng Y, Pinkerton AB, Hulea L, Zhang T, Cheli Y, Davies MA, Yin H, Lau E, Kim H, Barile E, De SK, Pellecchia M, Bosenberg M, Li JL, James B, Brown K, Topisirovic I, Ronai ZA. Cancer Res., (2015) Dec 15;75(24):5211-8.
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The translation machinery in cancer. Bhat M*, Robichaud N*, Hulea L*, Sonenberg N**, Pelletier J**, Topisirovic I** (* equally contributing; **co-corresponding). Nat Rev Drug Discov. (2015) Apr;14(4):261-78.
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Serine Deprivation Enhances Anti-neoplastic Activity of Biguanides. Gravel SP*, Hulea L*, Toban N*, Birman E, Blouin MJ, Zakikhani M, Zhao Y, Topisirovic I**, St-Pierre J**, Pollak M** (*equal contribution, **co-corresponding).Cancer Res. (2014) Dec 15;74(24):7521-33.
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Education
Postdoctoral fellowship in cancer biology, RNA translation, and cellular metabolism
Lady Davis Institute, McGill University, Montreal
PhD in biochemistry, transcriptional regulation and DNA damage
Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal
MSc in biochemistry
Université Claude Bernard Lyon 1, Lyon, France
Degree in engineering in biochemistry and biotechnology
Institut National des Sciences Appliquées, Lyon, France
Awards
- 2018 Travel award (Canadian Cancer Society)
- 2015 Travel award (Terry Fox Research Institute)
- 2008 Graduate studies award (Cole Foundation)
- 2008 Graduate studies award (Maysie MacSporran Award, McGill University)
- 2007 Graduate studies award (CIHR / McGill University)