Description of Research Expertise:
Research interest: Work in my laboratory is aimed toward the understanding of molecular pathways that govern chronic kidney disease development.
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.
Szu-Yu Li MD- Visiting Associate Professor
Kimberley Reidy MD- Adjunct Assistant Professor
Dorottya Laczko MD PhD - Postdoctoral fellow
Shizheng Huang PhD- Postdoctoral fellow
Jihwan Park PhD- Postdoctoral fellow
Caroline Gluck MD-Fellow
Yi-an Ko- Graduate Student
Chengxiang Qiu MS-Programmer
Frank Chinga- Research Specialist
Matthew Seasock- Research Specialist
Josh Bryer- Research Specialist
Transgenic expression of human APOL1 risk variants in podocytes induces kidney disease in mice.
Beckerman P, Bi-Karchin J, Park AS, Qiu C, Dummer PD, Soomro I, Boustany-Kari CM, Pullen SS, Miner JH, Hu CA, Rohacs T, Inoue K, Ishibe S, Saleem MA, Palmer MB, Cuervo AM, Kopp JB, Susztak K.
Nat Med. 2017 Feb 20. doi: 10.1038/nm.4287.
Sox9-Positive Progenitor Cells Play a Key Role in Renal Tubule Epithelial Regeneration in Mice.
Kang HM, Huang S, Reidy K, Han SH, Chinga F, Susztak K.
Cell Rep. 2016 Feb 2;14(4):861-71.
Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development.
Kang HM, Ahn SH, Choi P, Ko YA, Han SH, Chinga F, Park AS, Tao J, Sharma K, Pullman J, Bottinger EP, Goldberg IJ, Susztak K.
Cytosine methylation changes in enhancer regions of core pro-fibrotic genes characterize kidney fibrosis development.
Ko YA, Mohtat D, Suzuki M, Park AS, Izquierdo MC, Han SY, Kang HM, Si H, Hostetter T, Pullman JM, Fazzari M, Verma A, Zheng D, Greally JM, Susztak K.
Genome Biol. 2013;14(10):R108.
The Notch pathway in podocytes plays a role in the development of glomerular disease.
Niranjan T, Bielesz B, Gruenwald A, Ponda MP, Kopp JB, Thomas DB, Susztak K.
Nat Med. 2008 Mar;14(3):290-8.
Epithelial Notch signaling regulates interstitial fibrosis development in the kidneys of mice and humans.
Bielesz B, Sirin Y, Si H, Niranjan T, Gruenwald A, Ahn S, Kato H, Pullman J, Gessler M, Haase VH, Susztak K.
J Clin Invest. 2010 Nov;120(11):4040-54
Qiu Chengxiang, Huang Shizheng, Park Jihwan, Park YoSon, Ko Yi-An, Seasock Matthew J, Bryer Joshua S, Xu Xiang-Xi, Song Wen-Chao, Palmer Matthew, Hill Jon, Guarnieri Paolo, Hawkins Julie, Boustany-Kari Carine M, Pullen Steven S, Brown Christopher D, Susztak Katalin: Renal compartment-specific genetic variation analyses identify new pathways in chronic kidney disease. Nature medicine 24 (11): 1721-1731,2018.
Huang Shizheng, Park Jihwan, Qiu Chengxiang, Chung Ki Wung, Li Szu-Yuan, Sirin Yasemin, Han Seung Hyeok, Taylor Verdon, Zimber-Strobl Ursula, Susztak Katalin: Jagged1/Notch2 controls kidney fibrosis via Tfam-mediated metabolic reprogramming. PLoS biology 16 (9): e2005233,2018.
Katalin Susztak. Trends in molecular medicine 24 (8): 656-657,2018.
Beckerman Pazit, Susztak Katalin: APOL1: The Balance Imposed by Infection, Selection, and Kidney Disease. Trends in molecular medicine 24 (8): 682-695,2018.
Rosen Evan D, Kaestner Klaus H, Natarajan Rama, Patti Mary-Elizabeth, Sallari Richard, Sander Maike, Susztak Katalin: Epigenetics and Epigenomics: Implications for Diabetes and Obesity. Diabetes 67 (10): 1923-1931,2018.
Li Szu-Yuan, Susztak Katalin: The Role of Peroxisome Proliferator-Activated Receptor γ Coactivator 1α (PGC-1α) in Kidney Disease. Seminars in nephrology 38 (2): 121-126,2018.
Sharma Kumar, Susztak Katalin, Pennathur Subramaniam: Introduction: Systems Biology of Kidney Disease. Seminars in nephrology 38 (2): 99-100,2018.
Park Jihwan, Shrestha Rojesh, Qiu Chengxiang, Kondo Ayano, Huang Shizheng, Werth Max, Li Mingyao, Barasch Jonathan, Suszták Katalin: Single-cell transcriptomics of the mouse kidney reveals potential cellular targets of kidney disease. Science (New York, N.Y.) 360 (6390): 758-763,2018.
Zhao Juanjuan, Lupino Katherine, Wilkins Benjamin J, Qiu Chengxiang, Liu Jian, Omura Yasuhiro, Allred Amanda L, McDonald Caitlin, Susztak Katalin, Barish Grant D, Pei Liming: Genomic integration of ERRγ-HNF1β regulates renal bioenergetics and prevents chronic kidney disease. Proceedings of the National Academy of Sciences of the United States of America 115 (21): E4910-E4919,2018.
Qiu Chengxiang, Hanson Robert L, Fufaa Gudeta, Kobes Sayuko, Gluck Caroline, Huang Jing, Chen Yong, Raj Dominic, Nelson Robert G, Knowler William C, Susztak Katalin: Cytosine methylation predicts renal function decline in American Indians. Kidney international 93 (6): 1417-1431,2018.
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