Research in our laboratory is focused on cellular and molecular mechanisms regulating renal tubule electrolyte transport, with emphasis on regulation of acid-base transport in the thick ascending limb. The goals of our current research are to define how innate immune signaling pathways affect renal tubule function and to determine the role of these pathways in the impairment of thick ascending limb bicarbonate absorption and the pathogenesis of metabolic acidosis in sepsis. Our studies use an integrative approach that combines methods for direct study of ion transport and cell signaling in microdissected renal tubules with a clinically-relevant sepsis model to advance understanding of molecular mechanisms underlying sepsis-induced renal tubule dysfunction. In addition, we are investigating cellular mechanisms by which a novel therapeutic agent prevents sepsis-induced thick ascending limb dysfunction. These studies are designed to uncover new therapeutic targets that may aid in protecting renal tubule function during sepsis and a variety of inflammatory kidney disorders. This research has been supported continuously by NIDDK/NIH funding for more than 25 years