Work in my laboratory is aimed toward the understanding of molecular pathways that govern chronic kidney disease development.
Chronic Kidney Disease
Diabetic Kidney Disease
Epithelial cell differentiation
Work in my laboratory is aimed towards the understanding of molecular pathways that govern chronic kidney disease development. We have two general areas of interest: hypothesis generating (high trough-put, translational) and mechanistic studies. Over the past 10 years we banked and analyzed (combined genetic, epigenetic and genomic approaches) a large number of healthy and diseased human kidney tissue samples. 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 are specifically interested in defining cis-regulatory modules (promoters, enhancers and repressors) that govern the normal and altered epithelial phenotype in diseased kidneys.
In addition, we use genetic approaches and mouse as a model organism to test the role of candidate signaling molecules and regulatory pathways 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.
There are several; please speak with Dr. Susztak.
Jianling Tao MD- Visiting Associate Professor
Kimberley Reidy MD- Adjunct Assistant Professor
Esther Park MD - Postdoctoral fellow
Hyun Mi Kang PhD- Postdoctoral fellow
Mariya Sweetwyne PhD- Postdoctoral fellow
Laura Malaga MD, PhD-Fellow
Yi-an Ko- Graduate Student
Frank Chinga- Research Specialist
Nora Ledo- Research Specialist
Niranjan T, Bielesz B, Gruenwald A, Ponda MP, Kopp JB, Thomas DB, Susztak K.
The Notch pathway in podocytes plays a role in the development of glomerular disease. Nat Med. 2008 Mar;14(3):290-8. Epub 2008 Mar 2. PMID: 18311147
Kato H, Gruenwald A, Suh JH, Miner JH, Barisoni-Thomas L, Taketo MM, Faul C, Millar SE, Holzman LB, Susztak K. Wnt/β-catenin pathway in podocytes integrates cell adhesion, differentiation, and survival. J Biol Chem. 2011 Jul 22;286(29):26003-15. PMID: 21613219
Bielesz B, Sirin Y, Si H, Niranjan T, Gruenwald A, Ahn S, Kato H, Pullman J, Gessler M, Haase VH, Susztak K. Epithelial Notch signaling regulates interstitial fibrosis development in the kidneys of mice and humans. J Clin Invest. 2010 Nov;120(11):4040-54. PMID: 20978353
Sirin Y, Susztak K. Notch in the kidney: development and disease.
J Pathol. 2012 Jan;226(2):394-403 Review.
Woroniecka KI, Park AS, Mohtat D, Thomas DB, Pullman JM, Susztak K. Transcriptome analysis of human diabetic kidney disease. Diabetes. 2011 Sep;60(9):2354-69.
Susztak K : Understanding the epigenetic syntax for the genetic alphabet in the kidney. J Am Soc Nephrol 2014.
Han SH and Susztak K: : The hyperglycemic and hyperinsulinemic combo gives you diabetic kidney disease immediately Am J Physiol Cell Physiol 2014.
Reidy KJ, Kang HM, Hostetter TH and Susztak K: The Molecular mechanisms of diabetic kidney disease. J. Clin Invest 2014.
Beckerman P and Susztak K: Sweet debate: Fructose and diabetic kidney disease J Am Soc Nephrol 2014.
Dember L and Susztak K: Notch ties a knot on fistula maturation J Am Soc Nephrol 2014.
Hu C#, Mohtat D#, Yu Y^, Bhattacharya S^, Izquierdo MC, Gundabolu K, Ware K, Bhagat T, Heuck C, Nischal S, Saleh J, Suzuki M, Pullman J, Liu S, Greally JM, Susztak K*, Verma A* (*corresponding author): Kidney cancer is characterized by aberrant methylation of tissue-specific enhancers that are prognostic for overall survival. Clinical Cancer Research 2014.
Sweetwyne MT, Tao J, Susztak K: Kick it up a Notch: Role of Notch in Kidney Fibrosis. Kidney International Supplement 2014.
Beckerman P, Ko YA and Susztak K: : The cytosine methylation landscape of the kidney Nephrology Dialysis and Transplantation 2014.
Scharpf RB, Mireles L, Yang Q, Kottgen A, Ruczinski A, Susztak K, Halper-Stromberg E, Tin A, Cristiano S, Chakravarti A, Boerwinkle E, Fox CS, Coresh J, Kao WHL: Copy Number Polymorphisms Near SLC2A9 are Associated with Serum Uric Acid Concentrations BMC Genomics 2014.
Wing MR, Devaney JM, Joffe MM, Xie D, Feldman HI, Dominic EA, Guzman NJ, Ramezani A, Susztak K, Herman JG, Cope L, Harmon B, Kwabi-Addo B, Go AS, He J, Lash JP, Kusek JW, Raj D, : DNA Methylation Profile Associated with Rapid Decline in Kidney Function: Findings from the CRIC Study Nephrology Dialysis and Transplantation 2014.
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Last updated: 10/20/2014
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