Nephrology Research

Nephrology research spans the basic, translational and clinical areas of the discipline in order to understand the pathogenesis, diagnosis, prevention and treatment of chronic kidney diseases in humans during stages of growth and development.  Research is conducted both at the Stanley Manne Children's Research Institute and the Feinberg School of Medicine at Northwestern University.

Faculty

Jerome C. Lane, MD, has many research interests including (1) molecular determinants in children with D+ HUS; (2) home choice automated personal cycler with low fill mode drain logic and home choice low recirculation volume APD set with cassette for ESRD patients with fill volumes between 60ml and 1000 ml treated with peritoneal dialysis; (3) International Pediatric Peritonitis Study (IPPS); (4) Triptorelin for ovary protection in childhood lupus; (5) non-correlation of ionized calcium and ACT in pediatric patients undergoing continuous venovenous hemofiltration with regional citrate anticoagulation; (6) Focal Segmental Glomerulosclerosis clinical trial; (7) Focal Segmental Glomerulosclerosis Novel Therapies Study (FONT); (8) prolonged hemofilter use beyond 72 hours in pediatric continuous renal replacement therapy.

Craig B. Langman, MD, is the division chief and has devoted his entire career to the study of genetic diseases of children that produce metabolic bone disease, kidney stones, or other subtle forms of kidney disease. Specific research interests include: (1) genetic and acquired bone diseases of infants, children, and adolescents, and the effects of bone-specific therapy for them; (2) the osteodystrophy of chronic kidney disease, as a systemic disorder of bone and the vasculature; (3) kidney stone diseases, including the primary hyperoxalurias, Dent's disease, and disorders of the extracellular calcium-sensing receptor; (4) serving as a resource for measurement of bone and mineral homeostatic factors and agents, such as FGF-23, OPG, RANKL, TGF-β, inflammatory cytokines, and others.

Prior Research

The H. William Schnaper Laboratory studied the intracellular signals that mediate fibrosis in progressive kidney disease, using cultured mesangial cells as the model. These cells occupy a central location in the filters of the kidney, where they provide a support structure for the blood vessels entering the filter (also known as the glomerulus). In addition, mesangial cells may play a role in regulating the local production of soluble mediators that regulate many aspects of local cell function.

The central question: how does a fibrogenic hormone called transforming growth factor TGF-beta stimulate excessive extracellular matrix production by the mesangial cell? The immediate intracellular mediating molecules are members of the Smad signal transduction family. TGF-beta binds to its cognate receptor, which then activates the Smads to aggregate. The Smad complex is transported to the nucleus where it participates in the transcriptional activation of genes that encode for ECM and other proteins. Although the Smads are the only signaling molecules that the TGF-beta receptors are known to activate directly, researchers have identified many signaling pathways that are activated in mesangial cells after TGF-beta stimulation.

By understanding these interactions, we hope to identify ways to interrupt the signals that mediate ECM accumulation, and slow the scarring process in kidney disease. 

Tomoko Hayashida, MD, investigated the role of SMAD pathway in diabetic nephropathy. Her focus lies in determining the mechanism of "cross-talk" between the ERK and SMAD pathways and the role of TGF-ß1 signaling in human mesangial cell extracellular matrix production.