Schelling Lab

Beta 8 integrin in glomerular injury

Integrins are extracellular matrix receptors that are necessary for cellular migration, an important cell function during injury repair processes in response to disease. We have shown the beta 8 integrin expression is altered during Fas activation in tubular cells. In HEK293 cells, clustering and internalization of a GFP-tagged beta 8 integrin (IL-2 chimeric) activates small G protein signaling, which may participate in a regulatory pathway controlling fibrosis and scarring.

Wang Lab

Ephrin A2 regulates ureteric bud branching

Ephrin-Ephrin kinases mediate cell-cell contact signaling and are widely expressed in many epithelial cell types. We are studying the role Ephrins have in mammalian kidney development and in prostate cancer. Beta-gal staining of Epha2-lacZ knock out mouse kidneys indicated Ephrin A2 is expressed in the branching uretric bud and not in the condensing mesechyme or developing nephrons. The role Ephrins- Ephrin kinases have in controlling branching morphogenesis in kidney development and their signaling mechanisms are under investigation.

Sedor Lab

Discovery of Wilm's tumor interacting protein (WTIP)

Wilm's tumor-1 (WT-1) is a critical transcription factor for normal kidney development and differentiation of the podocyte. It is mutated in some forms of kidney cancer and other congenital renal diseases characterized by glomerulosclerosis. We have recently identified a WT-1 interacting protein (WTIP) that localizes at the plasma membrane with junctional complexes. WTIP has a nuclear localization signal, can translocate to the nucleus upon stimulation, and binds WT-1. The role this protein has in both regulating transcription and in functioning as a reporter of extracellular events is under investigation.

Simske Lab

Discovery of VAB-9, the first tetraspan adherens junction protein in C. elegans

Epithelial morphogenesis is regulated by the cell junction protein VAB-9. The wild-type C. elegans larva elongate smoothly into a familiar worm shape, whereas the vab-9 mutants have defects in epithelial cell shape, resulting in abnormal body morphologies, including pronounced tail defects. The interactions of VAB-9 with other junctional complex proteins is under investigation. We have also initiated studies on the recently identified vertebrate ortholog of VAB-9, TM4SF10, including characterization of its role in kidney development.

Bruggeman Lab

HIV-1 infects the kidney in HIV-Associated Nephropathy

We have recently shown that HIV-1 infects all renal epithelial
cell types in seropositive patients with HIV-associated nephropathy, a common AIDS complication in African Americans. The infection of both tubular and glomerular epithelial cells plays a direct role in pathogenic processes leading to cystogenesis and glomerulosclerosis. We are currently investigating how HIV-1 infection and HIV-1 gene expression in renal epithelia causes cellular dedifferentiation and induces apoptosis.

El-Meanawy Lab

Characterization of the Os mouse mutation

The ROP-Os mouse spontaneously develops glomerulosclerosis, although the genetic defect has remained uncharacterized. Using four probes/four color fluorescent in situ hybridization (FISH), the location and linear organization of the Os locus was found on chromosome 8 and represent a large inversion mutation. Studying the ROP-Os model will allow us to identify genes induced in the initiation and progression of glomerulosclerosis.

Sehgal Lab

Impact of quality improvement efforts on health disparities

Our research has focused on identifying and overcoming barriers to quality of care among hemodialysis patients. The figure shows changes in adequacy of hemodialysis dose by sex, through the years 1993-2001. The proportion of all patients receiving adequate hemodialysis increased two-fold while the gap between female and male patients decreased from 23% to 8%. Thus, quality improvement efforts may be useful in reducing health disparities.

Miller Lab

Signaling involving G protein-coupled receptors and Filamin A

We focus on signaling by the calcium-sensing receptor (CaR), a G protein-coupled receptor in epithelial cells that responds to extracellular Ca as well as other polycations. We found that the CaR interacts with filamin A, a cytoskeletal actin cross-linking protein that also acts as a scaffold for a number of signaling proteins. In the absence of filamin, of if the interaction of the CaR with filamin is disrupted, the CaR does not signal normally. We are trying to understand the precise role of filamin in organizing the multiple pathways controlled by the CaR. We are also beginning to study the role of filamin in protection of renal glomerular podocytes from mechanical injury.

This page was updated April 1, 2004.