Education:
BA 1986 Medicine - University of Cambridge, England
MD 1989 Medicine - University of Cambridge, England
Postdoctoral Research Fellowship:
1990 - 1993 Harvard Medical School, Brigham & Women's Hospital
Started at USC: 2002
Research Topics: Physiology, Membranes & Transport, Cell Structure & Organization
Research Description
Our primary interest is the physiology and molecular biology of renal tubular solute transport
The current focus of the laboratory is to understand the molecular and structural basis of paracellular epithelial transport and its regulation. Paracellular transport refers to transport in between cells. It is now well-recognized that paracellular transport is a major route for vectorial transport of solutes and water. The rate-limiting step in paracellular transport (the paracellular "barrier") is constituted by the tight junction, which is the most apical of the intercellular junctions. Tight junctions consist of large complexes of multiple different proteins. The claudins are a novel family of tight junction proteins that are postulated to form paracellular ion channels. If correct, claudins would likely be structurally and biophysically different from any known ion channels. There are at least 20 different claudin isoforms, raising the exciting possibility that isoform-specific expression may be responsible for the variability in paracellular permeability properties of different epithelial tissues.
Investigation of claudin physiology promises to reveal novel insights into the pathogenesis of clinical renal diseases associated with disturbances of the paracellular barrier, such as oliguric acute tubular necrosis, ischemic allograft dysfunction, and certain forms of salt-sensitive hypertension, including Gordon's syndrome. We are currently actively investigating the function of these proteins by overexpressing them in cell culture monolayers and performing electrophysiological and tracer flux measurements in Ussing chambers, by site-directed mutagenesis of key residues in the putative pore-lining region, and by generation of transgenic and knockout mouse models.
10 Selected Publications:
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Angelow S,Yu AS - Structure-function studies of claudin extracellular domains by cysteine-scanning mutagenesis. - J Biol Chem [2009] Aug 18;(): PubMed
Ahlstrom R,Yu AS - Characterization of the kinase activity of a WNK4 protein complex. - Am J Physiol Renal Physiol [2009] Sep;297(3):F685-92 PubMed
Ku E,Cheung EL,Khan A,Yu AS - Anion and osmolal gaps after alcohol intoxication. - Am J Kidney Dis [2009] Aug;54(2):385-8 PubMed
Angelow S,Yu AS - Cysteine mutagenesis to study the structure of claudin-2 paracellular pores. - Ann N Y Acad Sci [2009] May;1165():143-7 PubMed
Yu AS - Molecular basis for cation selectivity in claudin-2-based pores. - Ann N Y Acad Sci [2009] May;1165():53-7 PubMed
Yu AS,Cheng MH,Angelow S,Günzel D,Kanzawa SA,Schneeberger EE,Fromm M,Coalson RD - Molecular basis for cation selectivity in claudin-2-based paracellular pores: identification of an electrostatic interaction site. - J Gen Physiol [2009] Jan;133(1):111-27 PubMed
Günzel D,Yu AS - Function and regulation of claudins in the thick ascending limb of Henle. - Pflugers Arch [2008] Sep 16;(): PubMed
Yu AS,Kanzawa SA,Usorov A,Lantinga-van Leeuwen IS,Peters DJ - Tight junction composition is altered in the epithelium of polycystic kidneys. - J Pathol [2008] Sep;216(1):120-8 PubMed
Angelow S,Ahlstrom R,Yu AS - Biology of claudins. - Am J Physiol Renal Physiol [2008] Oct;295(4):F867-76 PubMed
Sabath E,Negoro H,Beaudry S,Paniagua M,Angelow S,Shah J,Grammatikakis N,Yu AS,Denker BM - Galpha12 regulates protein interactions within the MDCK cell tight junction and inhibits tight-junction assembly. - J Cell Sci [2008] Mar 15;121(Pt 6):814-24 PubMed
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