Current Research and Scholarly Interests
Dr. Bhalla received his training in molecular biology at UC San Francisco. His postdoctoral work centered on the regulation of aldosterone-mediated sodium transport in health and disease. In his laboratory he uses both in vitro and in vivo approaches for several projects related to the role of the kidney in health, diabetes, and hypertension.
(1) Diabetic kidney disease is costly and consequential. Diabetic kidney disease is the most common form of chronic kidney disease in the world, yet no curative therapy is available. Studies of the susceptibility of diabetic kidney disease led to the discovery of differential regulation of endothelial-specific molecule-1, Esm-1 (endocan) in susceptible strains of mice. Esm-1 is a secreted proteoglycan for which low levels in serum or glomeruli associate with worse kidney disease in both mice and humans. Rescue of Esm-1-deficient mice results in improvement in clinical and histologic markers of glomerular injury. Moreover, Esm-1 reverses gene expression of a host of glomerular cell-specific transcripts that correlate with albuminuria in diabetes. Ongoing experiments entail understanding the mechanisms of how Esm-1 confers protection against diabetic kidney disease; how serum and glomerular endothelial cell-derived Esm-1 differ in regulation, prognosis, and action; and the contribution of Esm-1 to other glomerular diseases.
(2) The laboratory has shown that tubular remodeling occurs in humans with selective disruption of segment-specific sodium and chloride transport. A related phenocopy occurs each day in pharmacology, i.e., inhibition of sodium reabsorption using diuretics is a mainstay of therapy for hypertension and edema-forming states. Study on the consequences of remodeling stimuli using tubular morphometry and single cell approaches have led to additional work on mechanisms of tubular remodeling in vivo.
(3) In the arena of clinical and translational research, Dr. Bhalla is interested in the role of aldosterone in the spectrum of hypertension, from primary aldosteronism to resistant hypertension. Dr. Bhalla has published on screening of primary aldosteronism and the need to better define aldosterone sensitivity.
