Éric A. Cohen
Study of HIV-host interactions governing HIV replication and persistence
- Professeur titulaire
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Faculté de médecine - Département de microbiologie, infectiologie et immunologie
Media
Portrait du chercheur
Le Dr Eric A. Cohen dans son Laboratoire de l'Institut de recherche cliniques de Montréal (IRCM).
© 2014 Université de Montréal
Consortium canadien de recherche sur la guérison du VIH (CanCURE)
Le Dr Éric A. Cohen est chef d'équipe de CanCURE. La mission de CanCURE est d’étudier les mécanismes régissant la persistance du VIH afin de mettre au point des stratégies thérapeutiques efficaces visant à guérir le VIH/sida.
© CanCURE
Profile
Research expertise
My laboratory focuses its investigations on the interactions between HIV-1 and immune cells that regulate viral replication, transmission, and persistence. The specific research projects currently conducted in the laboratory include:
- Studies of cellular restriction factors and role of HIV accessory proteins in the mechanisms of escape from innate/intrinsic immunity
- Studies of HIV-host interactions governing HIV replication and transmission in lymphoid and myeloid cells
- Humanized mouse as a model of HIV infection in vivo
- Role of host microRNAs in regulating HIV replication, transmission and persistence
These studies have the potential to enable the development of new therapeutic and vaccine strategies against HIV.
Methodology and approach
Given the scope of our research questions, we employ a wide variety of molecular biology, biochemistry, cell biology, and immunology techniques to study HIV pathogenesis. Individuals trained in our laboratory systematically acquire specialized knowledge in each of these experimental approaches. In addition to using human cell lines as a model, we use human primary immune cells, biological material sampled from individuals infected with HIV, in vivomodel of HIV infection in humanized mice, and gene disruption methods to study the function of specific genes in vivo. Our studies benefit from the technology platforms available at the Institut de recherches cliniques de Montréal (IRCM), including those put in place for virology (biocontainment laboratories at level 2 and 3), as well as those for immunology, genomics, proteomics, flow cytometry, microscopy, histology, transgenesis, and gene disruption.
Biography
Dr. Éric A. Cohen is Director of the Human Retrovirology unit at the Institut de recherches cliniques de Montréal (IRCM). He is also Professor of Virology at the Department of Microbiology, Infectiology and Immunology of the Faculty of Medicine of Université de Montréal and recipient of the Canada Research Chair in Human Retrovirology. Since 2009, he also serves as Leader of the Immunity and Viral Infection Research Division at the IRCM.
Dr. Cohen holds a B.Sc. in Biochemistry from McGill University and a Ph.D. in Molecular Biology from Université de Montréal (Ph.D. under the supervision of Dr. Yves Langelier). During his Postdoctoral training (under the supervision of Dr. William Haseltine) at the Dana Farber Cancer Institute at Harvard University, he contributed significantly to the global efforts to characterize the genetic organization and structure of the Human Immunodeficiency Virus (HIV). His initial work led to the discovery of two proteins, Vpr and Vpu, which belong to a class of HIV proteins, named accessory proteins, whose role is to promote viral persistence in spite of the host adaptive and innate/intrinsic immune responses. Dr. Cohen’s current research directions aim to better understand HIV-host interactions regulating viral replication, transmission, and persistence using state-of-the-art experimental approaches.
Since 2014, Dr. Cohen leads the Canadian HIV Cure Enterprise (CanCURE: www.cancurehiv.org), a pan-Canadian collaboration dedicated to the study of long-lived HIV reservoirs and the development of effective therapeutic strategies towards an HIV Cure. This scientific program is supported by the Canadian Initiative for HIV Cure Research, created through a partnership between the Canadian Institutes of Health Research (CIHR), the Canadian Foundation for AIDS Research (CANFAR), and the International AIDS Society (IAS).
Dr. Cohen is a member of numerous scientific committees, funding organizations, and international scientific journals. He is also author of over 135 manuscripts and books published in high-impact scientific and medical journals, as well as the holder of several international patents. Dr. Cohen is strongly involved in the Canadian and Quebec scientific community in the field of HIV/AIDS. He is a member of the Scientific Committee of the AIDS and Infectious Disease Network of the Fonds de recherche du Québec-Santé (FRQ-S). He is also a member of the Canadian Institutes of Health Research HIV/AIDS Research Advisory Committee (CHARAC). Dr. Cohen was awarded the Marcel-Piché Prize (2012) in recognition of the excellence of his research. He was also awarded the Pierre-Bois Prize (2014) for his valuable contributions to the development and promotion of the Institut de recherches cliniques de Montréal.
Awards and recognitions
- Membre, Académie des sciences, Société royale du Canada, 2016
- Membre, Académie canadienne des sciences de la santé, 2016
- Prix Pierre-Bois pour la promotion, la valorisation et le rayonnement de la recherche, Fondation de l'IRCM, 2014
- Prix Marcel-Piché, IRCM, 2012
- Chaire de recherche du Canada en rétrovirologie humaine (niveau 1), 2001-2015
education
- 1989 — Postdoctorat — Pathologie générale — Dana Farber Cancer Institute, Département de pathologie, Université Harvard
- 1987 — Doctorat — Biologie moléculaire — Université de Montréal
- 1983 — Maîtrise (sciences cliniques) — Biologie et autres sciences connexes — Université de Montréal
- 1981 — Baccalauréat — Biochimie — Université McGill
For more information…
- Page départementale d'Éric A. Cohen à l'Université McGill
- 2013-11-28 CanCURE : poursuivre la lutte contre le VIH
- CanCURE - Consortium canadien de recherche sur la guérison du VIH
- 21-10-2015 Éric A. Cohen devient titulaire d'une Chaire d'excellence de l'IRCM et de l'UdeM
- 07-09-2016 Quatre professeurs de l’UdeM entrent à la Société royale du Canada
- 18-08-2015 Dr. Éric Cohen et Dr. Mariana Bego, personnalités de la semaine de La Presse!
- 05-10-2014 Le Dr Éric A. Cohen se joint à l’IAS International Scientific Working Group: Towards an HIV Cure
- 15-07-2015 Le VIH se sert des outils propres au système immunitaire pour le détourner
- 19-07-2015 Sida: de nouveaux espoirs de guérison
Affiliations and responsabilities
Research affiliations
Research units
Titulaire
Membre
Affiliated institutions
- Institut de recherches cliniques de Montréal (IRCM)
Teaching and supervision
Student supervision
Theses and dissertation supervision (Papyrus Institutional Repository)
Étude du rôle des micro-ARN cellulaires au cours de l’infection par le VIH-1
Cycle : Doctoral
Grade : Ph. D.
Étude du rôle de CD47 comme nouvelle cible de la protéine Vpu du VIH-1 dans la pathogenèse virale
Cycle : Doctoral
Grade : Ph. D.
Étude de l'interactome et identification de nouvelles cibles de la protéine virale Vpr du VIH-1
Cycle : Doctoral
Grade : Ph. D.
Détection innée des cellules infectées au VIH-1 par les cellules dendritiques plasmacytoïdes : étude du rôle régulateur de la protéine Vpu de souches pandémiques et non pandémiques
Cycle : Master's
Grade : M. Sc.
La protéine accessoire Vpu du VIH-1 inhibe l'activité antivirale des pDCs à travers un processus ILT7-dépendant
Cycle : Master's
Grade : M. Sc.
Étude du rôle de la protéine Vpr du VIH-1 dans la modulation de la réponse immunitaire
Graduate : Richard, Jonathan
Cycle : Doctoral
Grade : Ph. D.
Étude du mécanisme d’augmentation de la relâche virale par la protéine Vpu du VIH-1
Graduate : Dubé, Mathieu
Cycle : Doctoral
Grade : Ph. D.
Manipulation of the ubiquitin-proteasome system by HIV-1 : role of the accessory protein Vpr
Graduate : Belzile, Jean-Philippe
Cycle : Doctoral
Grade : Ph. D.
Analyse du mécanisme de la dégradation du récepteur CD4 par la protéine Vpu du virus de l'immunodéficience humaine-1 (VIH-1)
Graduate : Binette, Julie
Cycle : Doctoral
Grade : Ph. D.
Capacité de rétention du récepteur CD4 par la protéine Vpu du VIH-1 chez des isolats primaires et implications au niveau de l'infectivité des particules virales
Cycle : Master's
Grade : M. Sc.
Analyse du trafic et de la distribution intracellulaire de la protéine Gag du VIH-1 dans les cellules HEK 293T : importance de l'efficacité de la relâche virale
Cycle : Master's
Grade : M. Sc.
Molecular and functional studies of human immunodeficiency virus type 1 accessory protein
Cycle : Doctoral
Grade : Ph. D.
Étude du trafic intracellulaire de la protéine Gag du VIH-1 : rôle des facteurs de l'hôte
Cycle : Doctoral
Grade : Ph. D.
Integrase, the central DNA flap and human immunodeficiency virus type 1 nuclear import
Cycle : Doctoral
Grade : Ph. D.
Conception d'une banque de nonapeptides exprimés constitutivement en cellules de mammifères pour l'étude in vivo d'interactions protéine-protéine
Cycle : Master's
Grade : M. Sc.
Étude du rôle des domaines structuraux et du motif de ciblage YXXO dans le transport intracellulaire et de l'activité fusogénique de la gp41 du VIH-1
Cycle : Doctoral
Grade : Ph. D.
Rôle de la protéine Vpu dans l'assemblage du VIH-1 au niveau des radeaux lipidiques
Cycle : Master's
Grade : M. Sc.
Rôle de la protéine virale Vpu dans le cycle de multiplication du virus de l'immunodéficience humaine de type 1 (VIH-1)
Cycle : Doctoral
Grade : Ph. D.
Caractérisation biologique de l'infection des cellules dendritiques thymiques par le virus de l'immunodéficience humaine de type 1 (VIH-1)
Cycle : Master's
Grade : M. Sc.
Étude du mécanisme d'incorporation de la protéine Vpr du Virus de l'Immunodéficience Humaine de type 1 (VIH-1) à l'intérieur des particules virales
Cycle : Master's
Grade : M. Sc.
Étude du mécanisme de transactivation de la protéine Vpr du virus d'immunodéficience humaine de type 1 (VIH-1)
Cycle : Doctoral
Grade : Ph. D.
Structural and functional characterization of the human immunodeficiency virus type-1 Vpr
Cycle : Doctoral
Grade : Ph. D.
Projects
Research projects
The Th17 Master Regulator RORC2 as a New Target for HIV Immune Therapy and Cure Strategy
Identification of Aryl Hydrocarbon Receptor as a Novel Druggable Modulator of HIV-1 Latency
Human immunodeficiency virus (HIV)-host interactions: from mechanisms of viral persistence to infection control
Canadian HIV Cure Enterprise 2.0: Targeting the interplay between myeloid cells and CD4+ T-cells for HIV cure
The Th17 Master Regulator RORC2 as a New Target for HIV Immune Therapy and Cure Strategy
Canadian HIV-Ageing Multidisplinary Programmatic Strategy (CHAMPS) in NeuroHIV
Exploring the role of the circadian clock in regulating HIV replication and viral reservoir reactivation in Th17 cells
Development of a safe, effective and clinically acceptable VSV-based HIV vaccine
Targeting of host antiviral and immune-modulatory factors by HIV-1 Vpu: Implications for viral pathogenesis and therapy
Interactions VIH-Hôte: des mécanismes de persistance virale au contrôle de l'infection
Réseau Sida et maladies infectieuses (SIDAMI) - Examining the role of pDC expansion in the control of HIV infection in humanized mice
Plasmacytoid dendritic cells in HIV infection
Examining the role of plasmacytoid dendritic cells in the control of HIV infection using humanized mice
Deciphering the functional role of Viral protein R (Vpr) during HIV infection
CanCURE. Consortium canadien de recherche sur la guérison du VIH/The Canadian HIV Cure Enterprise
Description
La mission de CanCURE est d’étudier les mécanismes régissant la persistance du VIH afin de mettre au point des stratégies thérapeutiques efficaces visant à guérir le VIH/sida. Nos démarches de recherche se concentrent sur le rôle et la contribution des cellules myéloïdes (c.-à-d. monocytes et macrophages) dans la persistance du VIH, un réservoir peu étudié, mais important pour le virus. Ce projet collaboratif combine les efforts d’éminents chercheurs canadiens, ainsi que d'un agent de liaison communautaire présentant le point de vue d’individus vivant avec le VIH. Le programme scientifique est basé sur quatre unités thématiques complémentaires de recherche.
- Le THÈME 1 définit les caractéristiques moléculaires, génétiques et fonctionnelles de la persistance du VIH/VIS dans des modèles humains et animaux, en se concentrant particulièrement sur les cellules myéloïdes.
- Le THÈME 2 étudie les mécanismes qui sous-tendent la latence et la persistance du VIH dans les cellules myéloïdes.
- Le THÈME 3 cherche à identifier de nouvelles drogues potentielles et des approches thérapeutiques capables d'éliminer l’infection persistante du VIH et à tester ces dernières au sein de modèles précliniques.
- Le THÈME 4 met en place une infrastructure adéquate afin de mener des essais cliniques en vue de guérir le VIH, en testant des immunothérapies visant à épuiser les réservoirs viraux chez des patients recevant une thérapie antirétrovirale.
De plus, les plateformes de recherche de CanCURE soutiennent l'équipe en donnant accès à des modèles animaux pertinents (Plateforme de modèles animaux), des tests de détection biologiques normalisés (Plateforme de développement de tests) et des ressources pour mener des études cliniques et translationnelles (Plateforme clinique). Les interactions entre les unités thématiques de recherche et les plateformes favorisent une approche multidisciplinaire et permettent de faire avancer la science vers notre objectif, celui de générer des interventions thérapeutiques efficaces contre la persistance du VIH chez des individus sous thérapie antirétrovirale.
THE CANADIAN HIV CURE ENTERPRISE (CANCURE)
THE CANADIAN HIV CURE ENTERPRISE (CANCURE)
Advancing Public Engagement in Canadian HIV Cure Research
DECIPHERING THE FUNCTIONAL ROLE OF VIRAL PROTEIN R (VPR) DURING HIV INFECTION
TOWARDS A TRANSFORMATIVE UNDERSTANDING OF HAND
HIV-1 VIRAL PROTEIN U (VPU) AS AN ANTAGONIST OF TETHERIN/BST2 : MOLECULAR MECHANISMS AND FUNCTIONAL IMPLICATIONS FOR VIRAL REPLICATION AND TRANSMISSION
HIV-1 Viral protein U (Vpu) as an antagonist of Tetherin / BST2 : molecular mechanisms and functional implications for viral replication and transmission
Description
AIDS is a slow degenerative disease of the immune and nervous systems resulting from HIV-1 infection. Despite considerable progress made in our understanding of HIV-1 infection, we still do not completely understand how the virus causes AIDS and how it maintains itself in infected individuals in presence of a vigorous immune response and highly suppressive antiretroviral regimens. Ultimately, our ability to control the AIDS pandemics, already destined to claim more than 33 million of lives world-wide, will depend on our ability to interrupt effectively viral replication, transmission and persistence by developing novel antiviral strategies and to render host antiviral immune responses more efficient at preventing viral infection by developing safe vaccine strategies. The HIV-1 vpu gene encodes a small integral membrane protein that is not found in HIV-2 and most simian immunodeficiency viruses. Vpu promotes the production of HIV-1 by antagonizing a newly identified interferon-regulated host restriction factor,called Tetherin / BST2, that retains newly formed virions at the surface of infected cells. The exact mechanisms underlying Tetherin antagonism by Vpu are yet to be elucidated. Furthermore, the role of Tetherin and Vpu in relevant cell targets of HIV-1 remains to be fully defined. Finally, given that the interaction of Vpu with Tetherin represents a potential therapeutic target, it is unclear whether HIV-1 can resist Tetherin restriction through Vpu-independent mechanism(s).
The goal of this research project will be to continue our investigation on the function and mode of action of Vpu to develop a better understanding of key HIV-1-host interactions regulating virus release and transmission.
Ultimately, elucidation of the interaction between HIV-1 Vpu and host innate defenses will lead to a heightened comprehension of viral replication and pathogenesis as well as suggesting additional targets for antiviral strategies.
Développement d’un modèle de souris humanisée pour l’étude de l’infection par le VIH
RECRUITEMENT OF THE DDB1-CUL4-DCAF1 E3 UBIQUITIN LIGASE COMPLEX BY THE HIV/SIV VPR/VPX ACCESSORY PROTEINS : IMPLICATIONS FOR VIRAL INFECTION, PERSISTENCE AND PATHOGENESIS
CHAIRE DE RECHERCHE DU CANADA EN RETROVIROLOGIE HUMAINE
Recruitment of the DDB1-CUL4-DCAF1 E3 ubiquitin ligase complex by the HIV/SIV Vpr/Vpx accessory proteins : implications for viral infection, persistence and pathogenesis
RESEAU SIDA ET MALADIES INFECTIEUSES (SIDAMI) - BANQUE SIRNA DE L'INFRASTRUCTURE GENOMIQUE DES FACTEURS DE L'HOTE
Outreach
Highlights
Hommage
Portrait de chercheur
For more information…
Publications and presentations
Publications
15 publications les plus significatives (révisées par un comité de pairs):
- Bego, M.G., Bérubé-Côté, É., Aschman, N. Mercier J., Weissenhorn, W. and Cohen, E.A. Vpu Exploits the Cross-Talk between BST2 and the ILT7 Receptor to Suppress Anti-HIV-1 Responses by Plasmacytoid Dendritic Cells. PLoS Pathog. 11(7):e1005024. July 2015. PMID 26172439.
- Pham, T.N.Q., Lukhele, S., Hajjar, F., Routy, J-P, and Cohen, E.A. HIV Nef and Vpu Protect HIV-Infected CD4+ T Cells from Antibody-Mediated Cell Lysis through Down-modulation of CD4 and BST2. Retrovirology 11: 15 2014. PMID: 24498878. Selected by Retrovirology as a highly accessed article
- Bego, M., Mercier, J., and Cohen, E.A. Virus-activated IRF-7 upregulates expression of the interferon-regulated BST2 gene independently of interferon signaling. Journal of Virology, 86(7): 3513-3527, 2012. PMID22301143.
- *Belzile, J-P, *Abrahamyan, L.G., Gerard, F. C., Rougeau, N., Cohen, E.A.Formation of mobile chromatin-associated nuclear foci containing HIV-1 Vpr and VPRBP is critical for the induction of G2 cell cycle arrest. PLoS Pathogens, 6(9) e1001080, 2010. PMID 20824083. CIHR. Featured on the cover of the September 2010 issue of PLoS Pathogens.
- Dubé, M., Roy, B.B., Guiot-Guillain, P., Binette, J., Mercier, J., Chiasson, A. and Cohen, E.A. Antagonism of Tetherin restriction of HIV-1 release by Vpu involves binding and sequestration of the restriction factor in a perinuclear compartment. PLoS Pathogens 6(4): e1000856, 2010. PMID 20386718 CIHR. Selected by Thomson Reuters ScienceWatch® as a featured New Hot Paper in Microbiology.
- Richard, J., Sindhu, S., Pham, T. NQ, Belzile, J-P and Cohen, EA. HIV-1 Vpr upregulates expression of ligands for the activating NKG2D receptor and promotes NK cell-mediated killing. Blood: 115(7): 1354-1363, 2010. PMID 20008788.
- *Belzile, J.-P., *Duisit, G., Mercier, J., Rougeau, N., Finzi, A. and Cohen, E.A. HIV-1 Vpr-mediated G2 arrest involves the DDB1-Cul4A VprBP E3 ubiquitin ligase. PLoS Pathogens. 3(7): e85, 2007. PMID 1914068.
- Lum, J.J., Cohen, O.J., Nie, Z., Weaver. J.G., Gomez, T.S., Yao, X.J., Lynch, D., Pilon, A.A., Hawley, N., Kim, J.E., Chen, Z., Montpetit, M., Sanchez-Dardon, J., Cohen, E.A. and Badley, A.D. Vpr R77Q is associated with long-term non-progressive HIV infection and impaired induction of apoptosis. Journal of Clinical Investigations 111(10): 1547-1554, 2003. PMID 12750404.
- Mouland, A.J., Mercier, J., Luo, M., Bernier, L., DesGroseillers, L. and Cohen, E.A. The double-stranded RNA-Binding protein Staufen is incorporated in human immunodeficiency virus type 1: Evidence for a role in genomic RNA encapsidation. Journal of Virology 74(12): 5441-5451, 2000. PMID 10823848.
- Subbramanian, R.A., Kessous-Elbaz, A., Lodge, R., Forget, J., Yao, X.J., Bergeron, D. and Cohen, E.A. Human immunodeficiency virus type 1 Vpr is a positive regulator of viral transcription and infectivity in primary human macrophages. Journal of Experimental Medicine 187(7): 1103-1111, 1998. PMID 9529326.
- Lodge, R., Lalonde J.P., Lemay, G. and Cohen, E.A. The membrane-proximal intracytoplasmic tyrosine residue of HIV-1 envelope glycoprotein is critical for basolateral targeting of viral budding in MDCK cells. The EMBO Journal 16(4): 695-705, 1997. PMID 9049299.
- Cohen, E.A., Dehni, G., Sodroski, J.G. and Haseltine, W.A. Human immunodeficiency virus Vpr product is a virion-associated regulatory protein. Journal of Virology 64(6): 3097-3099, 1990. PMID 2139896.
- Cohen, E.A., Terwilliger, E.F., Jalinoos, Y., Proulx, J., Sodroski, J.G. and Haseltine, W.A. Identification of HIV-1 Vpr product and function. Journal of Acquired. Immune Deficiency Syndrome 3: 11-18, 1990. PMID 2136707.
- Cohen, E.A., Terwilliger, E.F., Sodroski, J.G. and Haseltine, W.A. Identification of a protein encoded by the Vpu gene of HIV-1. Nature 334: 532-534, 1988. PMID 3043230.
- Cohen, E.A., Gaudreau, P., Brazeau, P. and Langelier, Y. Specific inhibition of herpes virus ribonucleotide reductase by a nonapeptide derived from the carboxy terminus of subunit 2. Nature 321: 441-443, 1986. PMID 3012360.
Disciplines
- Virology
- Molecular Biology
- Cell Biology
Areas of expertise
- Cell
- Gene (Living Organisms)
- Applied Genetics
- Genomics
- Diseases of the Immune System
- Sexually Transmitted Diseases (Infection and Immunity)
- Immune Reactions
- AIDS / HIV
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