Arohan R. Subramanya, M.D.

Potassium is the most abundant intracellular cation and is absolutely necessary for existence, as it participates in critical biological processes, including neuronal and cardiac function, and in the control of cell volume and systemic blood pressure. However, since even slight fluctuations of extracellular potassium outside of the normal range can be lethal, the ingestion of a dietary potassium load presents a daily challenge for mammals. The kidney plays a critical role in the regulation of total body potassium balance. My laboratory seeks to understand how the kidney carries out this process at the molecular level. Our work is focused on the WNK-SPAK/OSR1 pathway, a network of serine-threonine kinases that function as a molecular switch that drives a kidney’s decision to reabsorb or eliminate K+. We employ a molecule-to-organism approach that incorporates biochemistry, proteomics, molecular biology, gene editing, high resolution fixed and live cell imaging, and whole animal physiology to understand how signals in the kidney function during health and disease.

Our efforts to understand how WNK kinases work have prompted us to analyze how they have evolved over time. These ongoing studies have revealed novel mechanisms that control their activity, ranging from an ancient and unique role as intracellular chloride sensors, to their ability to organize into membraneless condensates in response to ionic stress. Our team is unraveling how these fundamental properties of the WNK signaling pathway are necessary for basic cellular function, and for life in general.