During both kidney development and disease progression, glomerular and tubular cells undergo multiple changes including proliferation, hypertrophy, apoptosis, cytoskeletal structure, and extracellular matrix synthesis and organization. Modulation of these functions is mediated by signal transduction pathways that are initiated by growth factors and/or cytokines binding to their cognate receptors in the target cells. Several groups in the Division of Nephrology are conducting research to better understand how signaling pathways regulate normal kidney development and the progression of several renal diseases.

One area of focus in our division is the role of the growth factor TGF-beta in regulating of renal fibrosis and cell apoptosis, features of some renal diseases. When TGF-beta binds to its specific receptors, signaling pathways involving Smad proteins are activated to regulate gene expression. A wide variety of approaches are employed to look at Smad signaling in kidney disease including the use of Smad2 and Smad3 knockout mice.

Another area of focus in the division is study of the role of a class of membrane receptors, erbB receptors, in normal renal development and progression of multiple forms of polycystic kidney disease (PKD). Previous studies demonstrated that one erbB family member, epidermal growth factor receptor (EGFR; erbB1), contributes to progression of PKD but the mechanism is currently unknown.

A third area of interest is determination of the mechanisms leading to HIV-associated nephropathy (HIVAN), which is produced by local HIV infection in the kidney. Nef, an HIV-1 accessory protein, is responsible for the podocyte proliferation and dedifferentiation observed in HIVAN. Studies implicate Src-Stat3 and MAPK ½ signaling pathways in mediating these Nef-dependent effects.