Overview

Neurons are highly vulnerable cells that narrowly rely on the brain’s highly dynamic and complex vascular network to assure an accurate and adequate distribution of nutrients and oxygen. The neurovascular unit constitutes a complex biological structure composed of different cell types that include neurons, endothelial cells, pericytes, astrocytes and microglia, which work in concert to enable proper brain homeostasis and functioning. Our research aims to decipher the molecular and cellular mechanisms underlying neurovascular interactions in cerebrovascular diseases and neurodegenerative disorders. Our ultimate goal is to develop novel therapeutic interventions that emphasize on targeting neurovascular interactions in brain disorders, as a gateway to promote brain tissue repair and regeneration.

Illustration: (a) The neurovascular unit is an interactive cellular network that comprises neurons, vascular cells and glial cells. (b) The neurovascular functions generated by endothelial cell and pericyte crosstalk under physiological and pathophysiological conditions. Adapted from Sweeney et al. (2016) Nature Neuroscience 19:771-83.

Our lab is particularly interested in investigating endothelial cell and pericyte interactions that generate critical neurovascular functions that include cerebral blood flow regulation, blood-brain barrier maintenance, angiogenesis, neurogenesis and immunomodulation. Endothelial cells form the blood-brain barrier and play an essential role in maintaining brain homeostasis. Pericytes are uniquely positioned at the interface between the brain vasculature and the brain parenchyma to integrate, coordinate and process signals from neighbouring cells. Moreover, pericytes are master regulators of vascular homeostasis, and have as well pleiotropic functions ranging from stromal to plastic properties.

Our research strategy consists on identifying and targeting specialized mechanisms regulating the functions of brain endothelial cells and pericytes in cerebrovascular diseases and neurodegenerative disorders to restore neurovascular functions.

Research approaches

Dr ElAli’s research program integrates cutting-edge molecular, cellular and imaging approaches to identify and evaluate the mechanisms associated to endothelial cell and pericyte functional remodelling in cerebrovascular diseases and neurodegenerative disorders. Established mouse models of stroke, cerebral small vascular disease, Alzheimer’s disease will be used. Gene editing combined with in vivo imaging will be applied. Advanced cell-based approaches will be used as well.

Research techniques

The following experimental techniques are regularly used including, microsurgery in mice, inducible Cre-Lox recombination in mice, Tet-on gene expression system in mice, TOPGAL reporter mice, perivascular reporter mice, chimeric mice generation, fluorescent microscope combined to optical sectioning via structured illumination (Apotome.2), laser Doppler flow measurements, laser speckle contrast imaging, primary endothelial and perivascular cell cultures, perivascular cell reprogramming (viral and non-viral), non-invasive brain cell transplantation, and live cell imaging. These techniques will be combined to immuno/histological and molecular techniques (WB, ELISA, rt-PCR, siRNA, shRNA). Finally, various techniques available through collaborations and platforms at our institution will be used, such as 2-photon intravital microscope, super-resolution microscopes (2P-STED, SPT-PALM, SLAM), cytometry platform equipped with conventional systems and a cutting-edge CyTOF system, as well as genomic (RNAseq, single cell RNAseq), proteomic and bioinformatic platforms.

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