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
Tin Adrienne, Marten Jonathan, Halperin Kuhns Victoria L, Li Yong, Wuttke Matthias, Kirsten Holger, Sieber Karsten B, Qiu Chengxiang, Gorski Mathias, Yu Zhi, Giri Ayush, Sveinbjornsson Gardar, Li Man, Chu Audrey Y, Hoppmann Anselm, O'Connor Luke J, Prins Bram, Nutile Teresa, Noce Damia, Akiyama Masato, Cocca Massimiliano, Ghasemi Sahar, van der Most Peter J, Horn Katrin, Xu Yizhe, Fuchsberger Christian, Sedaghat Sanaz, Afaq Saima, Amin Najaf, Ärnlöv Johan, Bakker Stephan J L, Bansal Nisha, Baptista Daniela: Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels. Nature genetics : 2019.
Chung Ki Wung, Dhillon Poonam, Huang Shizheng, Sheng Xin, Shrestha Rojesh, Qiu Chengxiang, Kaufman Brett A, Park Jihwan, Pei Liming, Baur Joseph, Palmer Matthew, Susztak Katalin: Mitochondrial Damage and Activation of the STING Pathway Lead to Renal Inflammation and Fibrosis. Cell metabolism 30 (4): 784-799.e5,2019.
Park Jihwan, Liu Chang Linda, Kim Junhyong, Susztak Katalin: Understanding the kidney one cell at a time. Kidney international 96 (4): 862-870,2019.
Salem Rany M, Todd Jennifer N, Sandholm Niina, Cole Joanne B, Chen Wei-Min, Andrews Darrell, Pezzolesi Marcus G, McKeigue Paul M, Hiraki Linda T, Qiu Chengxiang, Nair Viji, Di Liao Chen, Cao Jing Jing, Valo Erkka, Onengut-Gumuscu Suna, Smiles Adam M, McGurnaghan Stuart J, Haukka Jani K, Harjutsalo Valma, Brennan Eoin P, van Zuydam Natalie, Ahlqvist Emma, Doyle Ross, Ahluwalia Tarunveer S, Lajer Maria, Hughes Maria F, Park Jihwan, Skupien Jan, Spiliopoulou Athina, Liu Andrew, Menon Rajasree, Kang Hyun M: Genome-Wide Association Study of Diabetic Kidney Disease Highlights Biology Involved in Glomerular Basement Membrane Collagen. Journal of the American Society of Nephrology : JASN 30 (10): 2000-2016,2019.
Teumer Alexander, Li Yong, Ghasemi Sahar, Prins Bram P, Wuttke Matthias, Hermle Tobias, Giri Ayush, Sieber Karsten B, Qiu Chengxiang, Kirsten Holger, Tin Adrienne, Chu Audrey Y, Bansal Nisha, Feitosa Mary F, Wang Lihua, Chai Jin-Fang, Cocca Massimiliano, Fuchsberger Christian, Gorski Mathias, Hoppmann Anselm, Horn Katrin, Li Man, Marten Jonathan, Noce Damia, Nutile Teresa, Sedaghat Sanaz, Sveinbjornsson Gardar, Tayo Bamidele O, van der Most Peter J, Xu Yizhe, Yu Zhi, Gerstner Lea, Ärnlöv Johan, Danesh John: Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria. Nature communications 10 (1): 4130,2019.
Aranyi Tamas, Susztak Katalin: Cytosine Methylation Studies in Patients with Diabetic Kidney Disease. Current diabetes reports 19 (10): 91,2019.
Hellwege Jacklyn N, Velez Edwards Digna R, Giri Ayush, Qiu Chengxiang, Park Jihwan, Torstenson Eric S, Keaton Jacob M, Wilson O D, Robinson-Cohen Cassianne, Chung Cecilia P, Roumie Christianne L, Klarin Derek, Damrauer Scott M, DuVall Scott L, Siew Edward, Akwo Elvis A, Wuttke Matthias, Gorski Mathias, Li Man, Li Yong, Gaziano J Michael, Wilson Peter W F, Tsao Philip S, O'Donnell Christopher J, Kovesdy Csaba P, Pattaro Cristian, Köttgen Anna, Susztak Katalin, Edwards Todd L, Hung Adriana M: Mapping eGFR loci to the renal transcriptome and phenome in the VA Million Veteran Program. Nature communications 10 (1): 3842,2019.
Huang Shizheng, Sheng Xin, Susztak Katalin: The kidney transcriptome, from single cells to whole organs and back. Current opinion in nephrology and hypertension 28 (3): 219-226,2019.
Li Szu-Yuan, Chu Pao-Hsien, Huang Po-Hsun, Hsieh Tsung-Han, Susztak Katalin, Tarng Der-Cherng: FHL2 mediates podocyte Rac1 activation and foot process effacement in hypertensive nephropathy. Scientific reports 9 (1): 6693,2019.
Li Szu-Yuan, Park Jihwan, Guan Yuting, Chung Kiwung, Shrestha Rojesh, Palmer Matthew B, Susztak Katalin: DNMT1 in Progenitor Cells Is Essential for Transposable Element Silencing and Kidney Development. Journal of the American Society of Nephrology : JASN 30 (4): 594-609,2019.
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