Dennis Brown, PhD

Institution: Massachusetts General Hospital
Research: Regulation of Protein/Vesicle Trafficking in Epithelial Cells in Health and Disease
Grants & Publications: Harvard Catalyst
Categories: MGH

Dennis Brown is Director of the MGH Program in Membrane Biology (PMB) within the MGH Division of Nephrology. The overarching goal of the Program is to understand how epithelial cells respond to physiological cues, including the antidiuretic hormone vasopressin, to regulate their function in the kidney and other organs. The group studies how the processes of exo- and endocytosis work together to regulate the cell surface expression of critical cell membrane proteins, including aquaporin water channels and proton pumping H+ATPases. These proteins are central to organ function and systemic body fluid and acid base homeostasis. The role of cytoskeletal proteins such as tubulin, actin and accessory proteins in this process is a focus, as well as clathrin-mediated endocytosis. The role of hormonally induced phosphorylation of aquaporin 2 and other trafficking proteins, and identification and regulation of the kinases and phosphatases that regulate protein trafficking and kidney function in response to vasopressin is a central theme.

The experimental systems used in the PMB cover a wide range, moving from dissecting protein-protein interactions at the molecular level, through in vitro cell systems expressing normal and mutated purified proteins, to whole animal models including transgenic and knockout mice. The aim is to understand the physiological and hormonal regulation of fluid and electrolyte homeostasis in the context of renal function and disease. Representative projects include: 1) discovering new drugs and strategies to correct defective vasopressin receptor signaling that leads to increased (diabetes insipidus) or decreased (hypertension) urine output in disease; 2) dissecting the pathways and proteins involved in the recycling of a vacuolar (V-type) H+ATPase to regulate acid-base secretion, urinary tract acidification and proximal tubule function; 3) a new project to understand the role of inflammation mediated by collecting duct intercalated cells in the pathogenesis of acute kidney injury (AKI).