Schedule

Director of research and innovation, CHUM and Director of the CRCHUM

President and CEO, CHUM

Director of Vaccine Research, Infectious Diseases Division and Director, Institute for RNA Innovation, University of Pennsylvania. Co-laureate, Nobel Prize in Physiology or Medicine 2023 Nucleoside Modified mRNA-LNP Therapeutics Introduced by Sylvain Baillet

Assistant Professor, Department of Biochemistry and Functional Genomics at Université de Sherbrooke Unraveling the intricate crosstalk between pre-mRNA and snoRNA maturation Alternative splicing regulation plays a crucial role in development and disease. Yet, splicing of pre-mRNAs does not happen in isolation, but is functionally and physically connected to the maturation of small nucleolar RNAs (snoRNA). These short non-coding RNAs are often encoded in introns of longer genes, and their maturation requires excision of the snoRNA host intron through splicing. However, how these events influence one another is poorly understood. In this presentation, I will describe how we used specialized next-generation and nanopore sequencing approaches to analyze the expression and maturation of mRNAs and snoRNAs, and discuss the new insights gained on the crosstalk between mRNAs and snoRNAs during human neurogenesis and upon splicing inhibition. Introduced by Martine Tétreault

Perelman School of Medicine, University of Pennsylvania Design of Bespoke mRNA interventions for HIV Prevention and Cure Introduced by Andrés Finzi

Principal scientist and Theme leader, Immunopathology theme Professor, Department of microbiology, infectiology and immunology, Université de Montréal Paucity of HIV Envelope expressing cells upon latency reversal in ART suppressed PWH Antiretroviral therapy (ART) effectively suppresses HIV-1 replication but fails to eradicate the virus, as HIV-1 persists in long-lived reservoirs. Therefore, novel strategies are needed to detect and eliminate them. The HIV-1 envelope glycoprotein (Env) is the only viral antigen expressed on the surface of infected cells, making it a prime target for cure strategies. While current latency-reversing agents (LRAs) effectively induce the structural protein of the virus, their ability to stimulate Env expression remains unclear. We developed Env-Flow, a novel flow cytometry-based assay designed to measure surface Env expression on reservoir cells from people with HIV (PWH). Using this assay and a novel family of RNA-based LRA (developed by the Kreider and Weismann labs) we started to characterize these Env-expressing cells with the goal to uncover new vulnerabilities that could be exploited therapeutically. Strikingly, we observed a marked scarcity of Env expression after reactivation. Our results point towards a post-transcriptional block impairing Env expression. We are actively working to identify and overcome this block in order to better characterize, induce and ultimately eliminate Env-expressing cells as a part of HIV-1 cure strategies. Introduced by Nathalie Ouimet

Postdoctoral fellowTeam of Nicolas ChomontImmunopathology themeCRCHUM Leveraging RNA technology to reactivate and characterize the HIV reservoir Introduced by Nathalie Ouimet.

Shaping the future: RNA Research and Vaccine innovation Drew Weissman, M.D., Ph. D. Director of Vaccine Research, Infectious Diseases Division and Director, InstituteCo-laureate, Nobel Prize in Physiology or Medicine 2023 Jeff Guiler Director, Policy/Government Relations, Merck Canada Rahbar Rahimpour, PhD, MBA Director, R&D Strategic Alliances, Moderna Valérie Martel-Laferrière, MD, MSc Principal scientist, Immunopathology theme, CRCHUMMicrobiologist and infectious disease specialist, CHUMModerator: Andrés Finzi

Scientist, CRCHUM, Cancer ThemeHepatopancreatobiliary surgeon, CHUMHead of Immunocellular Therapy Research, CRCHUM Update on adjuvant personalized mRNA vaccine to prevent cancer recurrence Introduced by Nathalie Ouimet

Research AssociateTeam of Simon Turcotte, Cancer ThemeCRCHUM Cancer neoantigens beyond mRNA vaccine: new biomarker and development of adoptive T cell immunotherapy

Scientist, Neuroscience Theme, CRCHUM Associate Professor, Department of Neuroscience, University of Montreal RNA-sequencing in rare neurological diagnosis The development of next-generation sequencing (NGS) technologies led to the discovery of genetic causes for many inherited “Mendelian” diseases. Exome and Genome Sequencing approaches has led us to discover an increasing number of inherited variants in non-coding regions, where they exert their effects by altering mRNA processing and expression. Furthermore, current diagnostic tests often result in variant of uncertain significance precluding a clear diagnosis. Since the effects of these variants are not simple to predict, our capacity to discover new variants vastly exceeds our capacity to predict their functional and clinical impact. This results in 30-50% of rare disease cases without a molecular diagnosis after clinical and DNA-focus genetic investigations. RNA-sequencing complements DNA-level diagnosis by revealing the functional impact of variants on gene expression and splicing. Thus, providing insights on pathological mechanisms and a path out of diagnostic uncertainty.

Postdoctoral fellow, Team of Christine Vande Velde, Neurosciences Theme, CRCHUM The role of cryptic G3BP1 in ALS pathogenesis

Professor, Rosalind and Morris Goodman Cancer Institute, McGill University Director, Department of Biochemistry and Director, RNA Science Center, McGill University Towards Transcriptome-Informed mRNA medicines Introduced by Dr. Simon Turcotte

Research scientist in sociology, inserm From the Human Genome Project to the Clinic: Bringing Genomic Complexity to Patients The HGP came with several medical promises regarding diagnosis, prevention and treatment. However, twenty years later, despite the unprecedented development of sequencing tools, the ability to link genotype to phenotype has proven to be far more complex. Beyond its status as 'The Emperor of All Maladies' (Muhkerjee, 2010), cancer is a prime example of the hope surrounding sequencing technologies and the ongoing attempts to bring them to the clinic. Based on fieldwork conducted in France, this communication will focus on professionals' and patients' perspectives on the development of so-called genomic medicine. We will pay particular attention to how the complexity of molecular tools translates into clinical practice and affects healthcare inequalities. Introduced by Lise Gauvin

Director of Research and Innovation at the CHUM and Director of the CRCHUM