Group 3: integrative biology of ion transports (C. Duranton).

Axis 1: role of LRRC8 and CFTR/ABCC6 chloride channels in the human physiology

Chloride channels have always been underestimated principally due to the difficulties to characterize their molecular identities and by the absence of potent selective inhibitors. In this axis, we aim to characterize new and unexpected functions and roles of CFTR and LRRC8 (the most recently identified chloride channel family) in the modulation of cellular oxidative status in the context of various physiology and pathophysiology conditions such as inflammation, cystic fibrosis or kidney diseases.

Image groupe CD- axe1

 

Axis 2: ABCC6 and pyrophosphate metabolism in calcifying diseases

Arterial calcifications are a risk factor for cardiovascular morbidity and mortality. Arterial calcification corresponds to the deposition of hydroxyapatite crystals in the arterial walls due to an imbalance between procalcifying and anti-calcifying agents. Among the anti-calcification agents, pyrophosphate (PPi) play a major role and its concentration is related to the presence of a specific transporter (ABCC6). The objective of this clinical project is to understand how the circulating PPi level and ABCC6 expression/activity influence arterial calcification in various human pathologic situations.


Axis 3: innovative target to prevent ischemic-associated pathologies

The pharmaceutical industry needs new molecular targets validated in the field of ischemic / hypoxic pathologies. we demonstrated that targeting the newly identified signaling pathway (hypusination of EIF5A) increase the resistance of cells to hypoxia/ischemia. Our project is to extend this result to preclinical trials by applying it to organ transplantation and in the context of ischemic pathologies. We are also developing novel axis of research to increase hypoxic cellular tolerance from the targets we identified downstream and upstream of the EIF5A hypusination  pathway.