Associate Professor of Medicine
FRSQ Chercheur-boursier Senior
Member of Experimental Medicine
Molecular and cellular biology of HIV-1 and other retroviruses; RNA and cellular biology of HIV-1 replication; control of retroviral gene expression; retroviral assembly; viral evasion mechanisms.
HIV-1 RNA Trafficking Laboratory
Lady Davis Institute for Medical Research
3755 Côte-Ste-Catherine Road
Montreal, QC H3T 1E2
Tel: (514) 340-8260 x.4847
Fax: (514) 340-7502
andrew [dot] mouland [at] mcgill [dot] ca (Email)
*Currently accepting post-doctoral fellows and graduate students
Research Orientations and methods
My laboratory focuses on the molecular and cellular biology of retroviruses, in particular the human immunodeficiency virus type 1 (HIV-1), the causative agent of acquired immunodeficiency syndrome (AIDS). It is now established that HIV-1, like all viruses, commandeers major host machineries (e.g., transcription, translation, endosomal vesicle traffic) and coopts several host proteins for replication. One of our main research focuses is the further identification of host machineries and proteins involved in the fate and metabolism of HIV-1 RNAs. Specifically, we have identified several key cellular proteins that are involved in the fate of HIV-1 RNA in the cell. These proteins mark HIV-1 RNAs following their synthesis and are involved in the trafficking of HIV-1 RNAs from the nucleus into the cytosol, then to sites of viral assembly and finally, into the virus. Other proteins identified by members of the lab have important effects on the metabolism of HIV-1 RNAs in cells. We are also interested in identifying the protein-protein and protein-RNA interactions that occur in the infected cell between the host cell and the virus. Using biochemical, genetic, in vitro and in vivo techniques combined with digital imaging in fixed and live cells and biophysical assays such as bioluminescence resonance energy transfer and Bi- and Tri-molecular fluorescence complementation we are elucidating the mechanisms by which HIV-1 RNAs are directed to sites of viral RNA translation and viral assembly. These studies will likely lead to a better understanding of fundamental cellular processes (e.g, RNA trafficking, translation, metabolism) as well as to a more profound understanding on how HIV-1 is able to replicate.
A long term goal of our research is to identify and develop candidate compounds that could interrupt the processes involved in the trafficking of HIV-1 RNA during viral replication.
Selected Recent Publications
Levon Abrahamyan, Laurent Chatel-Chaix, Lara Ajamian, Miroslav P. Milev, Anne Monette, Jean-Francois Clément et al. 2010. Novel Class of Staufen1 Ribonucleoproteins Prevents Stress Granule Formation but Favours HIV-1 Genomic RNA Encapsidation. J. Cell. Sci. 123 (3): 369-383.
Anne Monette, Lara Ajamian, Marcelo Lopez-Lastra, Andrew J. Mouland. 2009. hnRNP A1 is retained in the cytoplasm in HIV-1 infected cells due to Nup62 degradation. J. Biol. Chem. 284(45): 31350-31362.
Martin Lehmann, Miroslav Milev, Levon Abrahamyan, X.-J. Yao, Nelly Pante and Andrew J. Mouland. 2009. Intracellular Transport of HIV-1 genomic RNA and Viral Production are Dependent on Dynein and Late Endosome Positioning. J. Biol Chem. 284 (21):14572-14585.
B.J. Hamilton, X-W Wang, J. Collins, A. Bergeron, B. Henry, B. Terry, M. Zan, Andrew J. Mouland and W.F. Rigby. 2008. Separate cis-trans pathways post-transcriptionally regulate murine CD154 (CD40 ligand) expression: a novel function for CA repeats in the 3' untranslated region. J. Biol. Chem. 283 (37):25606-25616.
Laurent Chatel-Chaix, Karine Boulay, Andrw J. Mouland* and Luc Desgroseillers*. 2008. Molecular determinants of Staufen1-mediated effects on human immunodeficiency virus type 1 assembly. Retrovirology5:41.
Lara Ajamian, Levon Abrahamyan, Miroslav Milev, Pavel V. Ivanov, Andreas E. Kulozik, Niels H. Gehring, and Andrew J. Mouland. 2008. UPF1 Unexpected roles for UPF1 in Human Immunodeficiency Virus type 1 RNA Metabolism and Translation. RNA 14:1-14.
Laurent Chatel-Chaix, Levon Abrahamyan, Andrew J. Mouland*, and Luc DesGroseillers*. 2007. The host protein Staufen1 participates in HIV-1 assembly in live cells by influencing pr55Gag multimerization. J. Virol. 81 (12): 6216-6230.
Cochrane, A.W., McNally, M., and Mouland, A.J. 2006. The Retrovirus RNA Trafficking Granule: From Birth to Maturity. Retrovirology 6 (3):18. (Review)
The laboratory
Dr. Mouland runs a medium-sized lab with young and highly talented molecular virologists who study the molecular biology of HIV-1. We have provided pioneering insights into the roles of host cell proteins and machineries involved in HIV-1 RNA fate. The lab is currently funded by several CIHR operating grants.
Examples of potential Ph.D. and PDF projects:
1) HIV-1 evasion of host RNA quality control machineries;
2) HIV-1 evasion of host stress responses;
3) Characterization of the Staufen 1 HIV-1-dependent ribonucleoproteins (SHRNPs); and
4) Medium- to high-throughput screening for host genes and machineries involved in the evasion of RNA quality control and stress responses.
Current members
Miroslav Milev, M.Sc. (Ph.D. candidate)
Anne Monette, M.Sc. (Ph.D. candidate), CIHR Doctoral Award recipient
Lara Ajamian, M.Sc. (Ph.D. candidate), CIHR Doctoral Award recipient
Bashar Ghoujal (M.Sc. candidate)
Kishanda Vyboh (M.Sc. candiate)
Lab members receiving degrees (degree obtained; current position)
Olivier Lavigueur (M.Sc.; M.D. at McGill University)
Lara Ajamian (M.Sc.; Ph.D. McGill University)
Martin Lehmann, M.Sc. (Research Trainee; Ph.D. University of Geneva)
Levon Abrahamyan, Ph.D. (PDF; Research Associate at Université de Montréal)
Laurent Chatel-Chaix (Ph.D.; PDF at Université de Montréal)
Viviane Poupon, Ph.D. (PDF; PDF at McGill University)
Jean-Francois Clément (M.Sc.; Ph.D./M.D. at Université de Montréal)
Véronique Bériault (M.Sc.; Industry)
Kathy Levesque (M.Sc.; Academia)
Kimberly Hu (B.Sc.; Industry)
Undergraduates, Honours students
Jennifer Allan (B.Sc.; Ph.D. Macdonald College of McGill)
Heather Gordon (B.Sc. Ph.D., Vet. Grad school)
Melanie Halvorsen (B.Sc., M.D., University of Ottawa)
Kimberly Hu
Jean-Francois Clément
Véronique Bériault
Jonathan Lachapelle