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| | | Patient-oriented and basic research are integral to the mission of the Division of Pediatric Kidney Diseases. Research is conducted both at the Children's Memorial Research Center and the Feinberg School of Medicine at Northwestern University. | | | | Our staff at 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. | | | The is located in the Children's Memorial Research Center 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. |  |  | | | | | | , 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. 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-ß1 signaling in human mesangial cell extracellular matrix production. has a primary research interest in determining the cellular mechanisms by which TGF-ß1 stimulates matrix accumulation in human mesangial cells. 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. , 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 Children's Memorial Hospital. His additional interests lie in childhood nephrotic syndrome and chronic renal insufficiency. has research interests in blood viscosity in hemodialysis patients and anemia management in dialysis patients. Current projects include studying iron treatment in dialysis patient, studying a new medication called cinacalcet in the treatment of bone osteodystrophy for children on dialysis. , 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. , 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. | | | | | | Effects of inter-dialytic weight gain and dialysis modality on BNP variability in children.
G Ariceta, P Pais, M.D, E.R. Brooks and C.B. Langman. Chronic Kidney Disease (CKD) in patients with osteoporotic fractures: An in-hospital experience.
B.J Edwards, M Vicuna and C.B. Langman. Fibroblast Growth Factor-23 (FGF-23) in children with Chronic Kidney Disease.
H.E. Price, C.B. Langman, E.R. Brooks, S Fathallah-Shaykh and A.E. Bobrowski. TGF-β1 induction of smooth muscle α-actin in human mesangial cells requires RhoA activation via an EGFR-dependent, ERK-independent pathway.
E.E. Sparks and H.W. Schnaper. Cdc42 activity is critical for Smad3-mediated induction of collagen I by TGF-β1.
E.E. Sparks, S.C. Hubchak and H.W. Schnaper. Focal adhesion composition and function in TGF-β/Smad-mediated mesangial cells production of type I collagen.
T Hayashida, M Wu, J Varga and H.W. Schnaper. Smad activity in stretch-induced human mesangial cell type I collagen expression: relation to transforming growth factor (TGF)-β-stimulated fibrogenesis.
J.F. Curley and H.W. Schnaper. Opposing roles of SARA and Dab2 in TGF-β1-mediated EMT.
C.E. Runyan, A Poncelet and H.W. Schnaper. Smad3 downregulation by TGF-[Beta]1 is limited to cells with a mesenchymal phenotype.
A Poncelet, C.E. Runyan, R Tan and Y Liu. FAK-mediated ERK phosphorylation requires P21-activated kinase in human kidney mesangial and epithelial cells.
S Jandeska, T Hayashida and H.W. Schnaper. |
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