Associate Professor - Professeur sous-octroi agrégé
ACCEPTING Post Doctoral Fellows AND GRADUATE STUDENTS
The research program of Dr. Rafei is focused on the theme of T-cell development and modulation. The following sections will briefly outline his three main research axes.
Stem cell transplantation (SCT) is an established modality for the treatment of hematological malignancies. However, it is hampered by slow and often incomplete T-cell reconstitution, which leads to the development of a restricted pool of peripheral T cells. We have recently discovered novel functions for certain cytokines in stimulating hemato-/thymopoiesis. Thus, our main goals are to: i) decipher their mechanism of action using several SCT models and transcriptome analyses, and ii) develop ex vivo expansion strategies for cord-blood-derived hematopoietic stem cells.
Axis 2. Developing a new type of antigen-presenting cell (APC) as an alternative to dendritic cells (DCs) for vaccination.
Mesenchymal stem cells (MSCs) have been often exploited in several medical applications including immunomodulation. For instance, potent conditional xenoantigen cross-presentation can be induced in MSCs following interferon-γ treatment. Such effect is believed to be due to increased expression of major histocompatibility complex (MHC)I on MSCs cell surface; a process concomitant with enhanced generation of peptides fragments by the proteasomal machinery. As the modulation of proteasomal activity can enrich peptides capable of snugly fitting MHCI grooves, we are engineering MSCs endowed with the capacity of eliciting powerful T-cell activation. Not only can these cells be used for cellular vaccination against cancer and infectious diseases, but they can be exploited as well as a cellular platform for the discovery of new xenoantigen-derived immunogenic peptides for vaccination purposes.
Axis 3. The discovery of small molecules for modulating the function of T cells and dendritic cells.
High-throughput screening is currently the mainstay for the identification of new pharmacological compounds. Using a newly developed in vitro murine fluorescent-based lymphocyte assay, my team has identified several hits with modulatory activities. Studies are currently ongoing to understand their pharmacological potential and molecular mechanism of action is order to exploit them in catastrophic illnesses.
- Tormo A et al. Interleukin-21 promotes thymopoiesis recovery following hematopoietic stem cell transplantation. J Hematol Oncol. 2017 Jun 14;10(1):120.
- Moutih Rafei, Jian Hui Wu, Borhane Annabi, Laurence Lejeune, Moïra François, and Jacques Galipeau. A GMCSF & IL15 fusokine leads to paradoxical immunosuppression in vivo via asymmetrical JAK/STAT signalling through the IL15 receptor complex. Blood. 2007: 109(5):2234-42.
- Moutih Rafei, Jeremy Hiseh, Elena Birman, MengYang Li, Annabi Borhane, Simon Fortier, Karen Doody, Michel Tremblay, Kathy Forner, Marie-Noelle Boivin, and Jacques Galipeau. Mesenchymal Stromal Cell Derived CCL2 Suppresses Plasma Cell Immunoglobulin Production via STAT3 Inactivation and PAX5 Induction. Blood. 2008. 112(13):4991-8
- Moutih Rafei, Philippe M. Campeau, Elena Birman, Kathy Forner, Jian Hui Wu, and Jacques Galipeau. Selective Inhibition of CCR2 Expressing Lymphomyeloid Cells in Experimental Autoimmune Encephalomyelitis by an Engineered Antagonist Chimeric GMCSF-MCP1 Fusokine. J. Immunol. 2009. 182(5):2620-7.
- Moutih Rafei, Philippe M. Campeau, Patrick Williams, Elena Birman, Shala Yuan, Christian Young, Marie-Noelle Boivin, Kathy Forner, and Jacques Galipeau. Mesenchymal Stromal Cells Ameliorate EAE by Inhibiting CD4 Th17 T-cells in a CCL2-dependent Manner. J. Immunol. 2009. 182(10):5994-6002.
- Moutih Rafei, Yamina Berchiche, Jian Hui Wu, Elena Birman, Nicolas Heveker, and Jacques Galipeau. An Engineered GMCSF-MCP1 Fusokine is a Potent Inhibitor of CCR2-driven Inflammation as Demonstrated in a Murine Model of Inflammatory Arthritis. J Immunol. 2009.183(3):1759-66.
- Moutih Rafei, Elena Birman, Kathy Forner, and Jacques Galipeau. Allogeneic Mesenchymal Stem Cells as Universal Donors for Treatment of Experimental Autoimmune Encephalomyelitis. Mol Ther. 2009. 17(10):1799-803.
- Moutih Rafei, Jeremy Hiseh, Simone Zehntner, MengYang Li,Kathy Forner, Elena Birman, Marie-Noelle Boivin, Josephine Nalbantoglu, Jacques Galipeau. AGMCSF/Interleukin-15 Fusokine Leads to the Generation of a Novel Type of Immune Regulatory B-Cell with Potent Immune Suppressive Properties as Demonstrated in the EAE Mouse Model of Multiple Sclerosis. Nat. Med. 2009. 15(9):1038-45.
- Moutih Rafei, Marie-Pierre Hardy, Patrick Williams, Juan Ruiz Vanegas, Kathy-Ann Forner, Gaël Dulude, Nathalie Labrecque, Jacques Galipeau, and Claude Perreault. Development and Function of Innate Polyclonal TCRαβ+ CD8+ Thymocytes. J. of Immunol. 2011,187(6):3133-44.
- Moutih Rafei, Marie-Noëlle Boivin, Elena Birman, Kathy Forner, and Jacques Galipeau. A GMCSF-MCP1 Fusokine with CCR2-Specific Tumoricidal Activity. Mol Cancer. 2011, 10:121.
- Moutih Rafei, Alexandre Rouette, Juan Ruiz Vanegas, Sylvie Brochu, and Claude Perreault. Differential Effects of γc-Cytokines on Post-Selection Differentiation of CD8 Thymocytes. Blood. 2013, 121(1):107-17
- Kamalika Mojumdar, Feng Liang, Christian Giordano, Christian Lemaire, Gawiyou Danialou, Tatsuma Okazaki, Johanne Bourdon, Moutih Rafei, Jacques Galipeau, Maziar Divangahi, Basil J. Petrof. Inflammatory monocytes promote progression of Duschenne muscular dystrophy and can be therapeutically targeted via CCR2. EMBO Mol Med. 2014. pii: e201403967.
- Al-Chami E. et al. Interleukin-21 Administration to Aged Mice Rejuvenates their Peripheral T-cell Pool by Triggering De Novo Thymopoiesis. Aging Cell. 2016. 15(2):349-60.