Laboratory of Humanized Models of Disease
The major research goal in our laboratory is to understand the molecular and cellular mechanisms that underlie Alzheimer's and other neurological diseases by using "humanized" mouse models of disease.
To generate these models, we used a combined approach that includes in vitro and in vivo tools of neurobiology and the pluripotent stem cell (ESC/iPSC) technology. More specifically, human pluripotent stem cells are first differentiated in vitro into neurons and/or glial cells (astrocytes, oligodendrocytes or microglia). Human neurons and glial cells generated in vitro are then xenotransplanted in the brain of rodent models of disease, where they are able to integrate functionally and can be exposed to amyloid-beta, Tau or other disease-related toxic factors. This technology allows us to study the responses of human glia and neurons exposed to disease-associated toxic factors at morphological, molecular and functional levels in a tridimensional environment as is the mouse host brain. By generating and characterizing these humanized mouse models, we intend to unravel human-specific pathways and mechanisms involved in the pathogenesis of Alzheimer's and other neurodegenerative diseases. These insights will ultimately lead to the development of new strategies for improved diagnostics and treatment.
In vitro culture and differentiation of human pluripotent stem cells (ESC/iPSC); Intracerebral grafting; Immunohistochemistry and immunofluorescence; Light, confocal and electron microscopy; Fluorescent-activated cell sorting; Immunoblotting; Rodent models of neurological diseases; Behavioural tests.