CECILE DUPLAA Role of Wnt/frizzled signaling in vessel organization and function
Course and current status
Cécile Duplàa Ph. D
Cécile Duplàa is Director of research at Inserm Center U1034 where she directs the team (Wnt/frizzled in vessel organization and function). She holds a PhD in vascular biology (1994, Bordeaux, France).
Before joining Inserm, she completed a residency in Pharmacy at Toulouse University Hospital. She then worked as a Fulbright post-doctoral research fellow at Boston Harvard Medical School , within Judath Folkman group. She returned to France as Junior Researcher at Inserm U441 in a group on the molecular and cellular mechanisms after ischemia. Since 2001, she directs a group at Inserm U1034 on the role of the Wnt/frizzled signalling in vascular formation and remodeling.
Scientific summary
Cécile Duplàaresearch focuses on investigating the nature of the Wnt signaling pathways and the molecular effectors acting during vascular morphogenesis. Her pioneer studies have identified that :
- Frizzled receptors participate in the maintenance of vascular integrity: loss of fzd7 increases vascular permeability via inactivation of the Wnt-canonical pathway in adult.
-Wnt/non canonical planar cell polarity (PCP) signaling regulates vascular remodeling in vertebrates: her group shed light onto the molecular mechanism that might underlie Wnt/PCP signaling function in important process directing embryonic and post natal remodeling of the vasculature in mouse.
- Technical advance: microCT vascular Imaging:her group has developed an innovative methodology for 3D visualization of the arterial macrovasculature by the use of a micro-CT (General Electric). The quantification of images in 3D, generated by mCT, enables them to understand the organization of the vessels and their functionality and to analyse angiogenesis and arteriogenesis processes.
- Wnt signaling was reported to modulate blood-retina and blood-brain barrier (BRB and BBB) integrity and to be required to induce maturation of the BBB tight junction properties in vitro and in vivo. her group has then addressed open questions about a functional role of the Wnt canonical signaling as a regulator in retinal post-natal angiogenesis and pathological retinal vascular pathology, about the contribution of Wnt non canonical signaling in the polarized vascular cell organization and in the maintenance of vessel integrity in pathological vascular cerebral disease outcome and extended this concept to cardiac function and failure.
- her scientific project focuses now on the search of new determinants of brain small vessel disease (SVD). SVD are shown to induce neurovascular unit dysfunction, and may be an early predictor of disease progression and potentially an added burden of neurodegeneration pathogenesis. therefore it is of major interest to delineate signaling pathways regulating the physiological functions of the neurovascular unit and gain insights into the pathological conditions causing loss or breakdown of the BBB.