High Blood Pressure, also called hypertension, is the largest contributor of premature death and disability in the world. Unfortunately, the basis of hypertension is unknown, and current treatment strategies are suboptimal. High dietary salt (NaCl) consumption has long been considered to be the primary culprit, but growing evidence indicates that low dietary potassium plays an equally important role. Our network unites leaders in the field to rapidly accelerate understanding of a new pathway that may explain the mysterious interaction between dietary potassium, salt-retention and blood pressure.

The Potassium Switch

WNK signaling

The “Potassium switch” concept was born out of the discovery of a genetic intolerance to sodium and potassium in humans, caused by mutations in the With-No-Lysine(K) kinases (WNK). Subsequent studies of our group and others revealed that WNK kinases orchestrate a switch response that toggles the activities of sodium and potassium transporters in the kidney to maintain sodium and potassium balance over widely varied potassium intake. Because low potassium consumption, common in modern diets, presses the pathway to conserve potassium at the expense of increasing sodium absorption, the switch provides a mechanism to explain how the modern diet feeds the fire of salt-sensitive hypertension. Our network unites leaders in the field with skills in gene editing, physiology, systems biology, molecular anatomy, and clinical-translational studies to rapidly accelerate understanding of this new pathway and identify new drug targets.

Research Projects

Blood Pressure

Blood Pressure and the Switch Pathway

Gene editing strategies and multifaceted state-of-the-art phenotyping in mice, combined with clinical-translational studies, are used to study how the switch pathway dictates the blood pressure responses to dietary sodium and potassium.

Molecular Cellular

Switch Pathway Biochemistry

Highly regulated interactions between kinases, phosphatases other signaling molecules have been proposed to regulate the switch. We have innovated new approaches to study these interactions in vivo for the first time.


Kidney Remodeling

Switch activation drives a remarkable structural remodeling process of the distal nephron. New organ clearing techniques and microscopic methods are being combined with genomic and proteomic approaches to identify and characterize the genes and pathways that underlie these processes.

Salt Hormone

Salt Retaining Hormone

Together with clinical studies in Human subjects, new mouse models have been developed and are being characterized to elucidate how the salt retaining hormone, aldosterone, controls the potassium switch.

Clinical Studies

Clinical-Translational Studies

The switch hypothesis is being explored in human subjects for the first time, testing how dietary potassium, aldosterone and inherited mutations in the switch pathway genes influence plasma potassium levels, switch activation and blood pressure.