Research Axis
Fetomaternal and Neonatal Pathologies Axis
Research Theme
Mechanisms for congenital anomalies
Address
CHUSJ - Centre de Recherche
Office 5.17.019
Phone
514 345-4931 7881
The laboratory is interested in the molecular mechanisms governing blood vessel morphogenesis in development and vascular diseases. Newly formed blood vessels are composed of endothelial tubes (EC) that migrate, proliferate, and become quiescent. The pericytes, surrounding the blood vessels, are also crucial for vascular quiescence and integrity. Maintaining vascular quiescence is, therefore, essential for human health, and its dysregulation will promote the onset and progression of several vascular diseases, including cancer and retinopathy. We are focusing on two main projects:
- TGFβ control of the EC proliferation in proliferative retinopathy. Proliferative retinopathies are currently treated with VEGF neutralizing antibodies, with limited therapeutic success. Therefore, it is crucial to identify new targets that could improve currently available treatments. TGFβ signaling is a significant regulator of the EC proliferation and the retina and brain blood vessels morphogenesis, and we are investigating the underlying mechanisms which are still poorly understood.
- Pericyte identity and function in development and proliferative retinopathy. We have recently identified a new pericyte paradigm proliferative retinopathy, whereby pathological pericytes (activated) promote pathological angiogenesis in oxygen-induced retinopathy (OIR), a mouse model that mimics some aspects of the retinopathy of prematurity (ROP). The laboratory aims to identify new molecular markers to target activated pericytes in proliferative retinopathy in order to develop new therapeutic strategies.
Career Summary
Dr. Alexandre Dubrac obtained his Ph.D. at Université de Bordeaux I, where he worked with Professor Andreas Bikfalvi on chemokines and tumor angiogenesis. Next, he joined Professor Anne Eichmann's group at the Cardiovascular Research Center at Yale University. As a postdoctoral fellow, he investigated the function of axon guidance regulators in angiogenesis and proliferative retinopathies. Among others, he has demonstrated that Slit2 and Robo1 & 2 are essential for developmental and pathological angiogenesis in the retina. Furthermore, he also studied the endothelial TGFβ/SMAD signaling in the arteriovenous malformations (AVM) of Hereditary Hemorrhagic Telangiectasias (HHT). In 2017, he was promoted as Associate Researcher at Yale University. He worked on the endothelial cell-pericyte interaction during the retinal vascular development and proliferative retinopathies. Dr. Dubrac was recruited in 2018 as a P.I. at the CHU Sainte-Justine Research Center and as an assistant professor in the Department of Pathology and Cellular Biology at the University of Montreal.