Biological membranes regulate fluxes of water and solutes over a 10,000-fold permeability range, from apical membranes of low permeability barrier epithelia to high permeability membranes which contain aquaporins or urea transporters. The Zeidel Laboratory has a long standing interest in epithelial physiology and in particular the barrier properties of certain epithelial cell membranes and the transport properties of several integral membrane proteins which facilitate water and solute passage across those membranes. The specialized epithelial cells which line the tubular network within the kidney and the luminal surface of the bladder (urothelium) have been studied in detail with central questions being;
1. how does the cell create and maintain a 'tight' or 'barrier' membrane?
2. what disease processes contribute to the breakdown of that barrier?
3. what are the molecular determinants which govern diffusive processes across lipid bilayers and cell membranes?
4. how do aquaporins and urea transporters function and how are they regulated?
Using approaches ranging from classical physiology to biophysical measurements of water, solute and gas fluxes to molecular studies of epithelial transporters facilitated by use of heterologous expression systems- the lab strives to answer basic scientific and clinically relevant questions.
Current research initiatives include (i) development of transgenic and conditional bladder knockouts in mice to explore cancer and interstitial cystitis pathways, (ii) the role of integrin cell and matrix adhesion proteins in the urothelium, (iii) the role that aquaporin 3 and the epithelial sodium channel play in normal bladder physiology, (iv) continuing investigations into the role of lipid structure in regulating bilayer permeability to gases, solutes and protons, (v) structure-function studies of urea transporters from bacteria to man which are currently yielding new insights into the pore and domain structures of this important class of proteins and (vi) the identification of novel genes and genetic loci which cause the onset of lower urinary tract syndrome with aging (the Center for Interdisciplinary Research in Benign Urology ).