Aurélie Edwards

 Research projects:

Our interest lies in developing mathematical models to investigate transport mechanisms in the kidney, at different levels (cell, tubule, organ). Our recent work focuses on (a) the regulation of calcium reabsorption along the different nephron segments; (b) the mechanisms by which the cortical collecting duct alternatively mediates the reabsorption or secretion of NaCl; (c) the interactions between nitric oxide, superoxide, and oxygen, and their effects on NaCl reabsorption in the renal medulla.

Simplified representation of intracellular calcium signaling in vascular smooth cells. Plasma membrane Ca²⁺ pumps (PMCA) and Na⁺/Ca²⁺ exchangers (NCX) mediate Ca²⁺ efflux, whereas voltage-operated Ca²⁺ channels (VOCa) carry Ca²⁺ in when activated by membrane depolarization.  Calcium stores in the sarcoplasmic reticulum (SR) are filled up by SR Ca²⁺ pumps (SERCA), and release Ca²⁺ into the cytosol via receptors that are sensitive to ryanodine (RyR) or inositol 1,4,5-trisphosphate (IP₃R). Agonist binding to G protein-coupled receptor leads to the formation of IP₃, thereby activating receptor-mediated Ca²⁺ release and triggering a signaling cascade. We developed a model of Ca²⁺ signaling in descending vasa recta (DVR) pericytes to elucidate the mechanisms by which angiotensin II generates cytosolic Ca²⁺ oscillations in DVR, as well as the effects of nitric oxide on DVR contraction.

 Schematic representation of rodent adrenal steroidogenesis.

We built a mathematical model of steroidogenesis in rodents to predict the effects of different diets on the production of aldosterone and corticosterone, as well as the intermediate  metabolites. The model predicted that mice increase their plasma progesterone levels specifically in response to potassium depletion. This prediction was subsequently confirmed by measurements in both male mice and men. Further investigation showed that  progesterone regulates the renal retention of potassium by stimulating the colonic H⁺,K⁺-ATPase in the kidney. 

Feedback mechanisms involving nitric oxide (NO), superoxide (O₂^-) and oxygen (O₂). Our studies aimed to elucidate the effects of NO and O₂^- on vascular and tubular functions in the renal outer medulla. NO synthesis is O₂-dependent, but red blood cell (RBC) trapping of NO may also decrease under hypoxic conditions, via uncertain mechanisms. NO is scavenged rapidly by hemoglobin (Hb), and to a smaller extent by O₂^-. The relationship between O₂^- synthesis and P_O2 remains unclear. Superoxide dismutase (SOD) consumes O₂^- at a faster rate than NO does. As a vasodilator, NO enhances medullary perfusion and O₂ supply, whereas O₂^- exerts opposite effects. NO inhibits NaCl reabsorption by the TAL and therefore O₂ consumption, whereas O₂^- stimulates both. Not shown on the diagram are the many other paracrine agents that act on vascular contraction and tubular NaCl reabsorption.