January 23, 2025
Dr. Allen Cowley, a Professor in the Department of Physiology at the Medical College of Wisconsin, and Dr. Ranjan Dash, a Professor in the Joint Department of Biomedical Engineering at Marquette University and the Medical College of Wisconsin, have been awarded a four-year, $2.67 million, MPI R01 grant renewal from the NIH National Heart, Lung, and Blood Institute in support of a project seeking to elucidate the underlying mechanisms of high-sodium diets on renal metabolic processes and their effects on hypertension and chronic kidney disease.
Excessive dietary salt is strongly linked to adverse cardiovascular and kidney outcomes, particularly in salt-sensitive individuals, who face a higher risk of developing hypertension and chronic kidney disease. This study explores how high salt intake affects kidney metabolism, with a focus on the renal cortex and proximal tubules, which are critical for sodium reabsorption and energy production.
The project titled “High Salt Remodels Renal Cortical and Proximal Tubular Metabolism: Metabolic Fuels, Oxidative Stress, and Hypertension,” seeks to uncover the bioenergetic, transcriptomic, and metabolomic differences linked to salt sensitivity using genetically engineered rat models and computational simulations. These investigations seek to clarify how the altered metabolic pathways and resultant mitochondrial oxidative stress contribute to kidney injury and hypertension.
By identifying therapeutic targets to reduce salt sensitivity, this study strives to advance our understanding of kidney intermediary metabolism and develop strategies to improve outcomes for salt-sensitive individuals.
Dr. Dash is the Director of the Computational Systems Biology Laboratory (CSBL) at the Marquette-MCW Joint Department of Biomedical Engineering. The lab focuses on developing advanced computational models to simulate biological functions and disease processes. By integrating experimental data, the lab uncovers molecular mechanisms, identifies therapeutic targets, and guides the development of new treatments. In this project, Dr. Dash’s lab collaborates with Dr. Cowley’s lab to develop multi-scale computer models to understand the metabolic basis of tubular dysfunction and kidney injury in salt-sensitive hypertension.
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