Mechanisms of Endothelial Regeneration and Vascular Repair: Application to Regenerative Medicine

Rony Chidiac, PhD
Research Associate
Department of Pharmacology and Physiology
Université de Montréal

This conference is hosted by Yasaman Aghazadeh, PhD. This conference is part of the the IRCM Early-Career Scientist Seminar Series (ECS3), a groundbreaking initiative whose mission is to showcase early career scientists. This is a great opportunity to discover the exciting projects of these researchers in training in front of a multidisciplinary audience.

About this conference : 
Dysregulation of signaling pathways that govern endothelial cell function is a hallmark of numerous vascular diseases. Targeting these pathways offers a promising strategy for regenerative medicine. We previously developed novel tailored antibody-based agonists with drug-like properties that mimic Wnt ligands and potently activate the Wnt/β-catenin pathway, which is essential for embryonic development and tissue homeostasis. We found that activating Wnt receptors in endothelial cells using our agonists repairs endothelial barrier leakage in vitro and restores pathological blood vessels in vivo. Our findings revealed a promising therapeutic approach for ocular diseases associated with abnormal angiogenesis and barrier dysfunction. These preclinical studies contributed to the development of an antibody that is currently in clinical trials for macular degeneration. Despite the potential of small molecules, improving the efficacy of vascular treatments remains a challenge, underscoring the need for innovative strategies. Leveraging the regenerative potential of human pluripotent stem cells, we have used small molecules and genomic screening to identify key bottlenecks in the differentiation of human embryonic stem cells into different lineages in vitro. Current differentiation protocols often yield heterogeneous endothelial populations with limited functionality, posing a challenge to the development of tissue-specific endothelial cells. My future research goal is to uncover the pathways and gene networks that can enhance the efficient differentiation of functional and mature tissue-specific endothelial cells for vascular repair in ischemic diseases. This work may hold the potential to revolutionize both cell therapies and drug development for ischemic vascular conditions.

About  Rony Chidiac : 
Le Dr Chidiac a obtenu son doctorat en pathologie et biologie cellulaire à l'Université de Montréal, où il a étudié la signalisation des cellules endothéliales dans l'angiogenèse. Au cours de sa formation postdoctorale à l'Université de Toronto, il a contribué au développement d'un anticorps novateur ciblant la voie Wnt, qui normalise les vaisseaux sanguins pathologiques dans des modèles de rétinopathie. Ces travaux ont conduit au développement d'un médicament actuellement en essai clinique pour les troubles oculaires. Le Dr Chidiac est l'auteur de nombreuses publications évaluées par des pairs, a reçu plusieurs prix, dont une subvention de recherche prestigieuse de la Fondation BrightFocus, et a présidé les Séminaires de Recherche Gordon sur la voie Wnt en 2023. Son objectif est de faire progresser les thérapies à base de cellules souches pour les maladies vasculaires.    Dr. Chidiac obtained his PhD in Pathology and Cell Biology from the Université de Montréal, studying endothelial cell signaling in angiogenesis. During his postdoctoral research at the University of Toronto, he contributed to the development of an innovative Wnt antibody that normalizes pathological blood vessels in retinopathy models. This work led to a drug currently in clinical trials for eye disorders. Dr. Chidiac has authored numerous peer-reviewed publications, received multiple awards including a prestigious research grant from BrightFocus Foundation and chaired the 2023 Wnt Gordon Research Seminars. His goal is to advance stem cell-based therapies for vascular diseases.