Katalin Susztak, M.D., PhD
Associate Professor of Medicine
University of Pennsylvania
538 Clinical Reserach Building
415 Curie Boulevard
Philadelphia, PA 19104
Medical: Semmelweis University, School of Medicine (MD 1995, PhD 1997), Budapest, Hungary
Residency: Albert Einstein College of Medicine, New York
Fellowship: Albert Einstein College of Medicine, New York
Board Certification: Internal Medicine, Nephrology
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. For further information visit our website: www.susztaklab.com-a.googlepages.com
Clinical and Other Interests:
Diabetic Kidney Disease
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)
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.
Kato H, Gruenwald A, Suh JH, Miner, JH, Barisoni L, Taketo MM, Faul C, Millar SE, Holzman LB, Susztak K: The Wnt/β-catenin pathway in podocytes integrates cell adhesion, differentiation and survival and plays a key role in maintaining the glomerular filtration barrier in mice J Biol Chem. 2011 Jul 22;286(29):26003-15.
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. Epub 2011 Jul 13.
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.
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]
Szabó C, Biser A, Benko R, Böttinger E, Suszták K.: Poly(ADP-ribose) polymerase inhibitors ameliorate nephropathy of type 2 diabetic Leprdb/db mice. Diabetes. 2006 Nov;55(11):3004-12.
Susztak K, Raff AC, Schiffer M, Böttinger EP. Glucose-induced reactive oxygen species cause apoptosis of podocytes and podocyte depletion at the onset of diabetic nephropathy. Diabetes. 2006 Jan;55(1):225-33.