The Department of Genetics and Pathogenesis of Cerebrovascular Diseases is part of Inserm. The department is committed to advance diagnosis, research and treatment options in inherited diseases affecting the brain vessels. One major focus of our research is on pathogenic mechanisms of monogenic form of cerebral SVDs. Our methodological expertise is in molecular, proteomic, structural and functional analysis of brain microvessels in genetically engineered mouse models using ex vivo and in vivo approaches. The department has a longstanding interest in CADASIL, the most frequent inherited SVD caused by dominant mutations in the NOTCH3 receptor, and has produced some of the seminal work in this field.
Inserm will lead WP3 (Microvascular matrisome and vascular integrity). In this WP, Inserm will identify changes in the extracellular matrix of brain microvessels in SVDs, shared by multiple SVDs as well as changes specific for individual SVDs and will determine whether and how these changes contribute to microvessel dysfunction and brain lesions. Inserm will also contribute to WP2 (analysis of blood brain barrier integrity in mouse models of monogenic forms of SVD), WP4 (proteomic analysis of vascular basement membranes), and WP5 (genetic manipulation of selected targets in the mouse for validation through interventions and in vivo analysis of cerebrovascular function).
Prof. Anne Joutel
Major field of research: SVDs; specific expertise in genetics, mouse models of SVDs, biochemistry, proteomics, electron microscopy and cerebrovascular physiology
Prof. Joutel has a longstanding interest in monogenic forms of SVDs and has produced seminal work on CADASIL and cerebrovascular function of Notch3 receptor. Her lab originally identified the Notch3 gene and delineated its role in CADASIL (Joutel et al. Nature 1995; Joutel et al. Lancet 1997). Her lab has developed and characterized multiple Notch3-related mouse models, including the first (and only) mouse model recapitulating most of the key features of CADASIL, as well as conditional and inducible mouse models of activation and inactivation of Notch in SMCs. She has initiated with Prof. Nelson (University of Vermont) a transatlantic research network on the pathogenesis of SVDs funded by the Fondation Leducq (website).
Prof. Joutel is a work package leader (WP3) in SVDs@target.
I am a Postdoc in Joutel's team, at IPNP (Paris). After my PhD in Neuroscience, I joined the research group to collaborate in CADASIL project. Our aiming is better characterize the accumulation of Notch3ECD receptor in the brain vessels of CADASIL mouse models. For that, techniques of immunohistofluorescence, electronmicroscopy, confocal/AiryScan imaging and cell quantification have been used.
Dr. Julien Ratelade
Dr. Hussein Kalakech
Mrs. Valerié Domenga