A team led by researchers from Mass General has uncovered key molecular step stones in alcohol-related liver disease that may provide targets for drug therapy development.
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About the Lab
The main focus in my laboratory is to study the mechanism of the trafficking of a water channel protein, AQP2. Specifically, we are investigating how AQP2 interacts with cellular trafficking machinery during endocytosis, exocytosis and recycling in cells; what the role of differential phosphorylation of AQP2 in regulated and constitutive recycling of AQP2, how polarity and extracellular matrix (ECM) affects the trafficking of AQP2. We are also interested in studying the mechanism of renal epithelial cell regeneration and differentiation during tubular repair/remodeling after tubular injury. We are taking comprehensive approaches and applying multiple model systems, including in vitro 3D culture, in vivo live image technology, in vitro organ culture, in vivo live image technology, in vitro organ culture/tissue slice culture, isolated kidney perfusion, mouse models and zebrafish models to study protein trafficking/epithelial polarity/remodeling in various kidney disease contexts.
My clinical interests are acute kidney injury, proteinuric kidney diseases, hypertension, electrolyte abnormalities and management of various chronic kidney diseases and dialysis.
Lu HA, Sun TX, Richard B, Blackburn K, McLaughlin M, and Brown D.Inhibition of endocytosis causes phosphorylation (S256)-independent plasma membrane accumulation of AQP2.Am J Renal Physiol.2004. 286:F233-F243.
Lu HA, Sun TX, Matsuzaki T, Yi XH, Eswara J, Bouley R, McKee M, and Brown D. Heat shock protein 70 interacts with aquaporin-2 (AQP2) and regulates its trafficking.J Biol Chem. 2007 Sep. 282(39): 28721-28732.
Paunescu TG, Da Silva N, Russo LM, McKee M, Lu HA, Breton S, and Brown D.Association of soluble adenylyl cyclase with the V-ATPase in renal epithelial cells.Am J Physiol Renal Physiol. 2008 Jan. 294(1): F130-F138.
Lu HA, Matsuzaki T, Bouley R, Hasler U, Qin QH, and Brown D.The phosphorylation state of serine 256 is dominant over that of serine 261 in the regulation of AQP2 trafficking in renal epithelial cells.Am J Physiol Renal Physiol. 2008 Jul. 295(1): F290 - F294.
Nunes P, Hasler U, McKee M, Lu HA, Bouley R, and Brown D.A fluorimetry-based ssYFP secretion assay to monitor vasopressin-induced exocytosis in LLC-PK1 cells expressing aquaporin-2.Am J Physiol Cell Physiol. 2008 Dec. 295(6): C1476-C1487.
Hasler U, Nunes P, Bouley R, Lu HA, Matsuzaki T, and Brown D.Acute Hypertonicity Alters Aquaporin-2 Trafficking and Induces a MAPK-dependent Acumulation at the Plasma Membrane of Renal Epithelial Cells. J Biol Chem. 2008 Sep. 283(39): 26643-26661.
Brown D, Nunes P, Hasler U, Bouley R, Lu HA. Phosphorylation events and the modulation of aquaporin 2 cell surface expression.Curr Opin Nephrol Hypertension. 2008 Sep. 17(5): 491-498.
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About the Nephrology Division
The Division of Nephrology at Massachusetts General Hospital is a leading provider of services for patients with kidney disease, including diagnosis and management of kidney diseases and medical management of renal transplantation.