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.
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.
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.
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.
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.