The Welling lab explores the genetic and molecular processes underlying potassium and sodium balance, hypertension, electrolyte abnormalities, and kidney disease. We use a multidisciplinary approach, spanning from gene discovery to molecular-cell and biochemical studies, to state-of-the art physiological studies in genetically engineered mice, to translational studies in human subjects.
The Potassium Switch
Potassium in Blood Pressure
Low dietary potassium consumption increases blood pressure, similar to high dietary sodium. We are investigating a new pathway, coined the renal potassium-switch, that explains the mysterious effects of potassium on blood pressure. Funded by the Foundation LeDucq Transatlantic Networks of Excellence Program, the project unites the Welling lab with other leaders in the field to rapidly accelerate the understanding of this new switch pathway from molecule to humans.
Blood potassium levels must be maintained within tight limits for many life functions, including regular heart rhythm, nerve impulses, and muscle contraction. We are unravelling the underlying mechanism, focusing on the key potassium regulatory pathways in the kidney that control the potassium excretory channel, ROMK (KCNJ1). Currently CRISPR and other gene editing approaches are combined with state-of-the-art physiological and cell biological phenotyping to genetically dissect the pathways.
Sodium Sensitive Hypertension
We are discovering how salt-sensitive hypertension develops at molecular, cellular and organ levels. Current investigations focus on kidney salt transport processes and their modulation by WNK kinase signaling pathways. This project enjoys a team science approach with Eric Delpire’s laboratory at Vanderbilt University.
Metabolism-Salt Transport Coupling
This new program builds on our surprising discovery of a metabolite activated salt retention pathway. Highly collaborative studies with Susan Wall, Emory and Eric Delpire, Vanderbilt are now genetically dissecting the pathway in mice and in vitro model systems to understand how potassium and other factors reprogram kidney metabolism to drive salt-sensitive hypertension and resistance to anti-hypertensive drugs.