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.
Tao J, Polumbo C, Reidy K, and Susztak K.: Tracing podocyte injury with a stochastic multicolor reporter highlights heterogeneous podocyte changes in focal segmental glomerulosclerosis. Kidney International November 2013.
Nihalani D and Susztak K: : Sirt1 in diabetic proximal tubules talks to podocyte claudin1 to regulate renal function. Nature Medicine November 2013.
Hackl M, Bunford JL, Villanueva K, Lam L, Susztak K, Schermer B, Benzing T, Peti-Peterdi J, : Tracking the fate of glomerular epithelial cells in vivo using serial multiphoton imaging in novel mouse models with fluorescent lineage tags. Nature Medicine November 2013.
Malaga-Dieguez L and Susztak K: : ADCK4; “reenergizes” nephrotic syndrome J. Clin Invest November 2013.
Ko YA*, Mohtat D*, Suzuki M*, Park ASD*, Izquierdo MC, Han SY, Kang HM, Si H, Gaikwad AB, Hostetter TH, Pullman J, Fazzari M, Verma A, Zheng D, Greally JM#, Susztak K#, : Cytosine Methylation Changes of Kidney Specific Gene Regulatory Regions in Chronic Kidney Disease Genome Biology October 2013.
Susztak K : Understanding the epigenetic syntax for the genetic alphabet in the kidney. J Am Soc Nephrol October 2013.
Ko YA, Susztak K#, : The science of no-longer-“junk” DNA. Why study it in chronic kidney disease?" Seminars in Nephrology July 2013.
Breyer MD, Coffman TM, Flessner MF, Fried LF, Harris RC, Ketchum CJ, Kretzler M, Nelson RG, Sedor JR, Susztak K; : National Dialogue (KRND). Diabetic Nephropathy: A National Dialogue. Clin J Am Soc Nephrol June 2013.
Sweetwyne MT, Susztak K: For better or worse: a niche for Notch in parietal epithelial cell activation. Kidney International June 2013.
Wang Y, Wu B, Chamberlain AA, Lui W, Koirala P, Susztak K, Klein D, Taylor V, Zhou B.: Endocardial to myocardial notch-wnt-bmp axis regulates early heart valve development. PLoS One. 2013;8(4):e60244., April 2013.
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Last updated: 07/14/2014
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