What We Do
High blood pressure (hypertension) affects over 1 billion people worldwide and is estimated to cause 7.5 million deaths annually. In most cases, the cause of hypertension is unknown, but rare forms caused by mutations in specific genes have also been identified. One such disease is Familial Hyperkalemic Hypertension (FHHt). Studying the mutated genes has led to the identification of a complex pathway that controls activity of a salt transporter (NCC) in the kidney. Our lab focuses on the the CUL3/KLHL3-WNK-SPAK/OSR1 pathway as a target for antihypertensive therapy. The disease familial hyperkalemic hypertension is caused by mutations in with-no-lysine (WNK) kinases 1 and 4 and in cullin-3 and kelch-like 3, components of an E3 ubiquitin ligase complex that promotes WNK kinase degradation. The study of the mechanisms by which this pathway regulates blood pressure has identified several candidates for the development of new antihypertensive agents.