Kidney Diseases 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.
Feinberg School of Medicine
The H. William Schnaper Laboratory studies the intracellular signals that mediate fibrosis in progressive kidney disease. We use as our model cultured human mesangial cells. 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.
Normally, there is a small amount of connective tissue called the extracellular matrix (ECM)--including collagen, laminin and other structural proteins--around the mesangial cells and the blood vessels. In a disease called focal segmental glomerulosclerosis (FSGS), the ECM accumulates, starting in the region around the mesangial cells. Our central question is: how does a fibrogenic hormone called transforming growth factor TGF-beta stimulate excessive ECM 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, we and other researchers have identified many signaling pathways that are activated in mesangial cells after TGF-beta stimulation.
We have determined that some of these other pathways play a significant role in TGF-beta -activated collagen production. Currently, we are investigating the mechanism by which these other pathways are activated, and how cross-talk among the pathways influences ECM gene expression. 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.
Stanley Manne Children's Research Institute
The Mineral Metabolism Lab is located in the Stanley Manne Children's Research Institute and is part of the Developmental Biology Program Core. Laboratory methods currently used include ELISA and RIA with PCR and Microarrays under development. The lab also works in conjunction with the clinical mass spectrometry laboratory in developing a new method for the detection of vitamin D2 and D3. The laboratory manager is Heather Price, MS, whose research interests include Fibroblast Growth Factor 23 (FGF-23) and hypophosphatemia, decreased Bone Mass Density (BMD) in Cystic Fibrosis, osteoclastogenesis (OPG and RANKL), vitamin D metabolism, and laboratory methods to determine indicators of bone metabolism.
Ellen Brooks, PhD, has many clinical research interests in the area of Chronic Kidney Disease. She is the principal and co-investigator on a number of clinical studies including (1) acute change in whole blood viscosity during hemodialysis; (2) differences in inflammation and oxidative stress in uropathy-related kidney diseases compared with glomerulopathy and in different ethnic backgrounds; (3) Brain Natiuretic Peptide (BNP) in pediatric patients with end-stage kidney disease and and in children receiving different types of dialysis; (4) dyslipidemia in Chronic Kidney Disease and renal transplant recipients. Dr. Brooks' other research interests include: (1) cardiovascular risk in the pediatric Chronic Kidney Disease population; (2) peak bone mass development and associated factors such as calcium and vitamin D intake, eating disorders, and exercise and body composition.
Tomoko Hayashida, MD is investigating 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-ÃŸ1 signaling in human mesangial cell extracellular matrix production.
H. William Schnaper, MD has a substantial basic science interest that is focused on how estrogen modulates endothelial cell signal transduction in blood vessel formation and atherosclerosis, and how mesangial cell responses to growth factors lead to scarring of the filters in the kidney.
Richard A. Cohn, MD, is currently the principal investigator for the North American Pediatric Renal Transplant Cooperative Study as well as the medical director of the kidney transplant program at Ann & Robert H. Lurie Children's Hospital of Chicago. His additional interests lie in childhood nephrotic syndrome and chronic renal insufficiency.
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-Î², inflammatory cytokines, and others.
For more specifics on the research activities being conducted in the Division of Kidney Diseases, please visit the division page on the Stanley Manne Children's Research Institute website.