Dennis Brown PhD
Dennis Brown is a Ph. D. cell biologist who specializes in the use of state-of-the art fluorescence imaging and electron microscopy techniques to follow and dissect physiologically-relevant membrane protein trafficking events in epithelial and non-epithelial cells. He serves as the Associate Director of the CSB and the Director of the MGH Program in Membrane Biology (PMB) which uses use state of the art technologies in the pursuit of important biological questions at the system level. He became Professor of Medicine at Harvard in 2001 and has been at MGH since 1985.
The theme of the PMB is to understand how endocytotic mechanisms (including clathrin and caveolae-mediated processes) and endosomal pathways interact with accessory proteins (e. g., small GTPases, SNAREs, adaptors) and with the cytoskeleton (e. g., microtubules, actin, and PDZ proteins) in physiological and pathophysiological conditions to regulate the trafficking of membrane proteins that are important to epithelial cell function in different organs. Experimental models used range from in vitro systems using purified proteins and membrane vesicles (endosomes, Golgi, plasma membrane), to transfected cell cultures, to whole animal models including transgenic mice and diabetic rats and mice.
The aim of the Program is to understand how physiologically-relevant processes that regulate fluid and electrolyte transport, acid-base sensing, albumin internalization and trafficking, and other metabolic events are regulated at the cell and molecular levels and how they are disrupted by disease. Representative projects include:
- Dissecting the mechanism by which water channel (aquaporin) trafficking occurs in renal epithelial cells in response to vasopressin. Kidney collecting duct principal cells respond to vasopressin by increasing the water permeability of their apical plasma membranes by exocytotic insertion of AQP2. We are examining the role of protein phosphorylation in this trafficking process using in vitro assays, transfected cell cultures, real-time microscopy, and in vivo animal studies;
- Understanding the pathways and proteins involved in the recycling of a vacuolar (V-type) H+ATPase in renal and urogenital tract to regulate renal acid-base secretion and urinary tract acidification;
- Elucidating the role of the V-ATPase and a soluble adenylyl cyclase as endosomal and extracellular pH sensors in epithelial cells;
- Dissecting the respective roles of changes in glomerular albumin permeability versus proximal tubule uptake of albumin in the development of albuminuria during diabetic nephropathy.