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.
Lee Ha Won, Khan Samia Q, Khaliqdina Shehryar, Altintas Mehmet M, Grahammer Florian, Zhao Jimmy L, Koh Kwihey, Tardi Nicholas J, Faridi Mohd Hafeez, Geraghty Terese, Cimbaluk David J, Susztak Katalin, Moita Luis F, Baltimore David, Tharaux Pierre-Louis, Huber Tobias B, Kretzler Matthias, Bitzer Markus, Reiser Jochen, Gupta Vineet: Absence of miR-146a in podocytes increases risk of diabetic glomerulopathy via upregulation of erbb4 and notch-1. The Journal of biological chemistry Dec 2016.
Bhagat Tushar D, Zou Yiyu, Huang Shizeng, Park Jihwan, Palmer Matthew B, Hu Caroline, Li Wejuan, Shenoy Niraj, Giricz Orsolya, Choudhary Gaurav, Yu Yiting, Ko Yi-An, Izquierdo Maria C, Park Ae Seo Deok, Vallumsetla Nishanth, Laurence Remi, Lopez Robert, Suzuki Masako, Pullman James, Kaner Justin, Gartrell Benjamin, Hakimi A Ari, Greally John M, Patel Bharvin, Benhadji Karim, Pradhan Kith, Verma Amit, Susztak Katalin: Notch pathway is activated via genetic and epigenetic alterations and is a therapeutic target in clear cell renal cancer. The Journal of biological chemistry Dec 2016.
Li Szu Yuan, Susztak Katalin: The long noncoding RNA Tug1 connects metabolic changes with kidney disease in podocytes. The Journal of clinical investigation 126(11): 4072-4075, Nov 2016.
Edeling M, Ragi G, Huang S, Pavenstädt H, Susztak K: Developmental signalling pathways in renal fibrosis: the roles of Notch, Wnt and Hedgehog. Nature Reviews: Nephrology 12(7): 426-39, Jul 2016.
Breyer MD, Susztak K: The next generation of therapeutics for chronic kidney disease. Nature Reviews: Drug Discovery 15(8): 568-88, May 2016.
Lin JS, Susztak K: Podocytes: the Weakest Link in Diabetic Kidney Disease? Current Diabetes Reports 16(5): 45, May 2016.
Akchurin O, Du Z, Ramkellawan N, Dalal V, Han SH, Pullman J, Müsch A, Susztak K, Reidy KJ: Partitioning-Defective 1a/b Depletion Impairs Glomerular and Proximal Tubule Development JASN 27(12): 3725-3737, May 2016 Notes: [Epub ahead of print]
Li SY, Susztak K: Fat Burning Problem in Cystic Kidneys: an Emerging Common Mechanism of Chronic Kidney Disease. EBioMedicine 5: 22-3, Mar 2016.
Ledo N, Susztak K, Palmer M: Cell Phenotype Transitions in Renal Fibrosis. Current Pathobiology Reports Page: 19-25, Mar 2016.
Teumer A, Tin A, Sorice R, Gorski M, Yeo NC, Chu AY, Li M, Li Y, Mijatovic V, Ko YA, Taliun D, Luciani A, Chen MH, Yang Q, Foster MC, Olden M, Hiraki LT, Tayo BO, Fuchsberger C, Dieffenbach AK, Shuldiner AR, Smith AV, Zappa AM, Lupo A, Kollerits B, Ponte B, Stengel B, Krämer BK, Paulweber B, Mitchell BD, Hayward C, Helmer C, Meisinger C, Gieger C, Shaffer CM, Müller C, Langenberg C, Ackermann D, Siscovick D, Boerwinkle E, Kronenberg F, Ehret GB, Homuth G, Waeber G, Navis G, Gambaro G, Malerba G, Eiriksdottir G, Li G, Wichmann HE, Grallert H, Wallaschofski H, Völzke H, Brenner H, Kramer H, Leach IM, Rudan I, Hillege JL, Beckmann JS, Lambert JC, Luan J, Zhao JH, Chalmers J, Coresh J, Denny JC, Butterbach K, Launer LJ, Ferrucci L, Kedenko L, Haun M, Metzger M, Woodward M, Hoffman MJ, Nauck M, Pruijm M, Bochud M, Rheinberger M, Verweij N, Wareham NJ, Endlich N, Soranzo N, Polasek O, van der Harst P, Pramstaller PP, Vollenweider P, Wild PS, Gansevoort RT, Rettig R, Biffar R, Carroll RJ, Katz R, Loos JF, Hwang SJ, Coassin S, Bergmann S, Rosas SE, Stracke S, Harris TB, Corre T, Zeller T, Illig T, Aspelund T, Tanaka T, Lendeckel U, Völker U, Gudnason V, Chouraki V, Koenig W, Kutalik Z, O'Connell JR, Parsa A, Heid IM, Paterson AD, de Boer IH, Devuyst O, Lazar J, Endlich K, Susztak K, Tremblay J, Hamet P, Jacob HJ, Böger CA, Fox CS, Pattaro C, Köttgen A: Genome-wide Association Studies Identify Genetic Loci Associated with Albuminuria in Diabetes. Diabetes 65(3): 803-17, Mar 2016.
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Last updated: 12/21/2016
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