Twenty million Americans suffer from chronic diabetic and non-diabetic kidney diseases that cause the kidneys to fail. When kidneys fail, the average life expectancy is just over two years and survival depends on costly and disabling dialysis or transplantation treatments.
Work in my laboratory is aimed towards the understanding of renal fibrosis and chronic kidney disease development. We are performing translational (hypothesis generating) and mechanistic studies. The aim of our translational research work is identify novel, genetic, genomic and epigenenomic biomarkers of chronic renal disease. We collected large number control and diseased human kidney tissue samples, which we are using for genome wide transcriptome and epigenomics (mainly cytosine methylation) analysis. We hypothesize that integrative analysis of epigenetic and genetic settings in diseased cells can provide a rational basis for more accurately modeling the critical biological pathways involved in mediating the progressive phenotype in individual patients. We also predict that epigenomic integrative analysis can be used to determine the identity of chromatin and transcription factors that contribute mechanistically to aberrant transcriptional programming in chronic kidney disease, and that this information can be used for designing therapeutic strategies.
We use genetic approaches and mice as a model organism to test the role of candidate signaling molecules directly in vivo. The Cre/loxP and tet inducible transgenic technologies allow us to analyze the function of particular factors by deleting or overexpressing genes that encode them in specific cell types in the kidney. Specifically, we are working on determining the role of the Notch and Wnt/beta-catenin pathway in chronic kidney disease development, renal epithelial cell homeostasis, renal stem or progenitor cell function and differentiation. Our recent results highlight the role of embryonic programs in adult disease development.
Visit our website: www.susztaklab.com-a.googlepages.com
Thiruvur N, Bielesz B, Gruenwald A, Ponda M, Kopp J, Thomas D, Susztak K The activation of the Notch Pathway in Podocytes Plays a Role in the Development of Glomerular Disease Nature Medicine 2008 Mar;14(3):290-8. Epub 2008 Mar 2 (Editorial; News and Views on pp246 – 247)
Lorenzen J, Shah R, Biser A, Staicu S, Niranjan T, Garcia AM, Gruenwald A, Thomas D, Shatat I, Supe K, Woroniecki R, Susztak K; The role of Osteopontin in the development of albuminuria Journal of the American Society of Nephrology 2008 May;19(5):884-90.
Si H, Banga RH, Shah R, Biser AE, Lawrence J, Gruenwald A, Glicklich D, Tellis V, Bottinger EP, Greenstein S, Schechner R, Thomas DB, Pullman J, Fazzari M, Susztak K The Human and Murine Kidney shows Gender- and Species-Specific Gene Expression Differences in Response to Injury PLoSONE 2009;4(3):e4802.
Brosius FC, Alpers CE, Bottinger EP, Breyer MD, Coffman TM, Gurley SB, Harris RC, Kakoki M, Kretzler M, Leiter EH, Levi M, McIndoe MA, Sharma K, Smithies O, Susztak K, Takahashi N, Takahashi T; for the Animal Models of Diabetic Complications Consortium, Mouse Models of Diabetic Nephropathy, Journal of the American Society of Nephrology 2009 Dec;20(12):2503-12. Epub 2009 Sep 3. (Review)
Murea M, Park JK, Sharma, S, Kato K, Gruenwald A, Niranjan T, Si H, Thomas DB, Pullman J, Melamed ML, Susztak K: Expression of Notch Pathway Proteins Correlated with Albuminuria, Glomerulosclerosis and Renal Function Kidney International 2010 August (cover article) [Epub Jun 9.ahead of print]
Chua SC, Li Y, Liu SM, Liu R, Chan KT, Martino J, Susztak K, Zheng Z, D’Agati V, Gharavi AG: Mapping a Susceptibility Gene for Diabetic nephropathy to Mouse Chromosome 8 in db/db FvB/NJ, a Robust Mouse Model of Diabetic Kidney Disease Kidney International 2010 Jun 2. [Epub ahead of print]
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