Description of Research Expertise

Research interest
Work in my laboratory is aimed toward the understanding of molecular pathways that govern chronic kidney disease development.

Keywords
Chronic Kidney Disease
Diabetic Kidney Disease
Tissue fibrosis
Genomics
Epigenomics
Notch, Wnt/Ctnnb1
Epithelial cell differentiation

Research details

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.

Rotation Projects
There are several; please speak with Dr. Susztak.

Lab Personnel:

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

Selected Publications:

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.