Jeff Sands, MD
Juha P. Kokko Professor of Medicine
Director, Renal Division
(404) 727 - 2525
My research is directed at understanding the physiology of the renal inner medulla and the urine concentrating mechanism. Current research projects are focused on defining the molecular physiology of urea transporters since urea transport is a key component in the urine concentrating mechanism. These studies use models of abnormal concentrating and diluting ability, such as diuretic rats (water or furosemide diuresis), adrenalectomized rats, or rats with diabetes mellitus. I use a combination of isolated perfused tubule studies to measure urea transport, antibodies to measure changes in the amount, location, phosphorylation, or localization of the urea transport proteins, and Northern analysis and real-time PCR to measure changes in mRNA, and surface biotinylation and confocal microscopy to measure changes in the subcellular localization of urea transporters. I, in collaboration with Dr. Klein and the late Dr. Robert Gunn, made stably-transfected polarized epithelial cell lines, UT-A1-MDCK, UT-A2-MDCK, UT-A3-MDCK, and UT-A4-MDCK, that express each of the renal UT-A splice isoforms individually. These cells are models of the renal inner medullary collecting duct (for UT-A1 and UT-A3) and the thin descending limb (for UT-A2). These cells can be used to determine the kinetic relationships between functional urea transporters, the membrane into which they are inserted (apical vs. basolateral), their activation by phosphorylation or other modifications, and their regulation. I have also made cell lines expressing mutated urea transporters that can be used to determine critically important portions of the molecule for folding, surface expression and transport.