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 that is enriched in glomerular endothelium and inhibits LFA-1 : ICAM-1 interaction and decreases infiltration in glomeruli in the setting of diabetes and other inflammatory diseases. Ongoing rescue and deletion experiments explore the role of Esm-1 in diabetes and diabetic kidney disease. We also study the regulation of Esm-1 transcription and protein stability.
(2) Investigation of the mechanisms of hypertension in the setting of obesity and insulin resistance using renal tubular epithelial insulin receptor deletion challenged the role of insulin in the hypertension of obesity, insulin resistance, and the metabolic syndrome. These studies also shed light on the role of insulin in control of glucose reabsorption via SGLT2. Ongoing studies focus on molecular mechanisms of insulin-regulated SGLT2 and its contrast with insulin resistant pathways in other cell types and tissues.
(3) An unexpected finding of aberrant regulation of potassium transport in obesity and insulin resistance has led to another project exploring the role of obesity and insulin in potassium transport in the cortical collecting duct.
(4) A major regulator of sodium reabsorption, Clcnkb, is mutated in humans with Barrter's syndrome, Type 3. However, surprisingly little is known about the regulation of this channel in health and disease. Ongoing experiments include the study of post-translational regulation of Clcnkb surface expression and activity using in vitro and in vivo approaches.
(5) Inhibition of sodium reabsorption using diuretics is a mainstay of therapy for hypertension and edema-forming states. Study on the consequences of diuretic therapy using tubular morphometry and single cell approaches have led to additional work on mechanisms of tubular remodeling in vivo.
