The primary goal of this proposal is to explore the hypothesis that the Notch pathway plays an important role in the development of diabetic nephropathy. We found via large scale genome screening that Notch pathway proteins are regulated in animal models of diabetic nephropathy. In vitro studies showed that the hyperglycemic milieu activates the Notch pathway and this activation leads to the dysfunction of glomerular cells. These observations suggest that the Notch pathway plays an important role in mediating diabetic complications.
The specific aims of the proposal are to:
Aim one is to characterize the molecular mechanism of glucose induced Notch pathway activation in podocytes. In the second specific aims we will determine the role of Notch pathway activation in glucose induced podocyte dysfunction. We will achieve this aim via genetic manipulation of Notch signaling. Under the third specific aim we will determine the in vivo functional role of glomerular epithelial Notch in mediating the development of diabetic nephropathy via the use of genetically engineered animals. In the long-term, this work will elucidate molecular signaling mechanisms determining specific, context dependent cellular responses, such as apoptosis and growth arrest that may be triggered by hyperglycemia in different cell types.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Pathobiology of Kidney Disease Study Section (PBKD)
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Rys-Sikora, Krystyna E
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Albert Einstein College of Medicine
Internal Medicine/Medicine
Schools of Medicine
United States
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Li, Szu-Yuan; Park, Jihwan; Qiu, Chengxiang et al. (2017) Increasing the level of peroxisome proliferator-activated receptor ? coactivator-1? in podocytes results in collapsing glomerulopathy. JCI Insight 2:
Beckerman, Pazit; Qiu, Chengxiang; Park, Jihwan et al. (2017) Human Kidney Tubule-Specific Gene Expression Based Dissection of Chronic Kidney Disease Traits. EBioMedicine 24:267-276
Beckerman, Pazit; Bi-Karchin, Jing; Park, Ae Seo Deok et al. (2017) Transgenic expression of human APOL1 risk variants in podocytes induces kidney disease in mice. Nat Med 23:429-438
Scerbo, Diego; Son, Ni-Huiping; Sirwi, Alaa et al. (2017) Kidney triglyceride accumulation in the fasted mouse is dependent upon serum free fatty acids. J Lipid Res 58:1132-1142
Ko, Yi-An; Yi, Huiguang; Qiu, Chengxiang et al. (2017) Genetic-Variation-Driven Gene-Expression Changes Highlight Genes with Important Functions for Kidney Disease. Am J Hum Genet 100:940-953
Breyer, Matthew D; Susztak, Katalin (2016) The next generation of therapeutics for chronic kidney disease. Nat Rev Drug Discov 15:568-88
Kang, Hyun Mi; Huang, Shizheng; Reidy, Kimberly et al. (2016) Sox9-Positive Progenitor Cells Play a Key Role in Renal Tubule Epithelial Regeneration in Mice. Cell Rep 14:861-871
Teumer, Alexander; Tin, Adrienne; Sorice, Rossella et al. (2016) Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes. Diabetes 65:803-17
Breyer, Matthew D; Susztak, Katalin (2016) Developing Treatments for Chronic Kidney Disease in the 21st Century. Semin Nephrol 36:436-447
Edeling, Maria; Ragi, Grace; Huang, Shizheng et al. (2016) Developmental signalling pathways in renal fibrosis: the roles of Notch, Wnt and Hedgehog. Nat Rev Nephrol 12:426-39

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