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Wednesday, March 08, 2017 6:27:16 AM
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.
Axis 1. Novel pharmacological strategies to improve T-cell reconstitution. 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-? 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.
https://www.mcgill.ca/microimm/people/adjuncts/rafei-moutih
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