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Mathieu's research has always focused on the link between RNA and disease. He first completed a Master's degree working on the evolution of HIV-1 and HCV, two RNA viruses, in Prof. Hugo Soudeyns' lab at CHU Sainte-Justine. He then completed a Ph.D. on the regulation of alternative RNA splicing in the laboratories of Prof. Benjamin Blencowe and Prof. Sabine Cordes at the University of Toronto. These studies established for the first time a causal link between RNA splicing defects and autism disorders. During his postdoctoral training with Prof. Kristen Lynch and Prof. Yoseph Barash at the University of Pennsylvania, he developed and applied bioinformatics tools for transcriptomic analyses to identify novel immunotherapy targets in cancer. His lab is now further pursuing this research to refine and expand the molecular profiling of therapeutic targets, and experimentally validate candidates.