Aquaporin (water channel) trafficking: we are dissecting the mechanisms of water channel (aquaporins 1, 2, 4 and 9) trafficking and regulation in epithelial cells from the kidney and male reproductive tract. These channels play a crucial role in maintaining body fluid homeostasis, and the specific functions of diverse organ systems including the eye, ear, brain and reproductive tract.
Vacuolar H+ATPase (proton pump) trafficking and regulation: specialized proton secreting epithelial cells are involved in acid-base regulation in the kidney and in sperm maturation in the epididymis. We have identified a soluble adenylate cyclase (sAC) as a sensor of extracellular pH and bicarbonate in the epididymis and vas deferens, and are examining the role of this protein in pH sensing by cells in general.
Endocytotic mechanisms in renal tubular cells: endocytosis of filtered proteins (albumin) is a major function of the renal proximal tubule that is perturbed in disease states, including diabetes. This leads to loss of albumin in the urine. We are using in vitro systems and animal models to explore proximal tubule receptor mediated endocytosis of albumin with the aim of discovering new strategies for treating albuminuria.
pH sensing in endosomes: endosomes respond to intravesicular acidic pH by recruiting cytosolic coat components that regulate their trafficking. We have recently identified the H+ATPase as an endosomal pH sensor and we are determining its role in coat recruitment and vesicle trafficking in the protein degradative pathway in epithelial cells.
G-protein coupled receptor trafficking and signaling: we are using diverse microscopic (FRET), biochemical, molecular and pharmacological tools to understand how G-protein coupled vasopressin and PTH receptors signal upon ligand binding. These receptors are involved in various critical aspects of fluid and electrolyte balance, mainly via actions on kidney epithelial cells.
Regulation of iron metabolism: this is a complex process that involves many proteins that bind to and transport iron in and out of cells in a highly coordinated manner. Recently, we established a fundamental link between bone morphogenic protein (BMP) signaling and iron metabolism. By studying this complex but important signaling pathway, we hope to shed light on iron dysregulation diseases such as hemochromatosis and anemia of chronic disease.