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
Chu Audrey Y, Tin Adrienne, Schlosser Pascal, Ko Yi-An, Qiu Chengxiang, Yao Chen, Joehanes Roby, Grams Morgan E, Liang Liming, Gluck Caroline A, Liu Chunyu, Coresh Josef, Hwang Shih-Jen, Levy Daniel, Boerwinkle Eric, Pankow James S, Yang Qiong, Fornage Myriam, Fox Caroline S, Susztak Katalin, Köttgen Anna: Epigenome-wide association studies identify DNA methylation associated with kidney function. Nature communications 8 (1): 1286,2017.
Han Seung Hyeok, Wu Mei-Yan, Nam Bo Young, Park Jung Tak, Yoo Tae-Hyun, Kang Shin-Wook, Park Jihwan, Chinga Frank, Li Szu-Yuan, Susztak Katalin: PGC-1α Protects from Notch-Induced Kidney Fibrosis Development. Journal of the American Society of Nephrology : JASN 28 (11): 3312-3322,2017.
Beckerman Pazit, Qiu Chengxiang, Park Jihwan, Ledo Nora, Ko Yi-An, Park Ae-Seo Deok, Han Sang-Youb, Choi Peter, Palmer Matthew, Susztak Katalin: Human Kidney Tubule-Specific Gene Expression Based Dissection of Chronic Kidney Disease Traits. EBioMedicine 24 : 267-276,2017.
Seki Yoshinori, Suzuki Masako, Guo Xingyi, Glenn Alan Scott, Vuguin Patricia M, Fiallo Ariana, Du Quan, Ko Yi-An, Yu Yiting, Susztak Katalin, Zheng Deyou, Greally John M, Katz Ellen B, Charron Maureen J: In Utero Exposure to a High-Fat Diet Programs Hepatic Hypermethylation and Gene Dysregulation and Development of Metabolic Syndrome in Male Mice. Endocrinology 158 (9): 2860-2872,2017.
Bajaj Archna, Susztak Katalin, Damrauer Scott M: APOL1 and Cardiovascular Disease: A Story in Evolution. Arteriosclerosis, thrombosis, and vascular biology 37 (9): 1587-1589,2017.
Li Szu-Yuan, Park Jihwan, Qiu Chengxiang, Han Seung Hyeok, Palmer Matthew B, Arany Zoltan, Susztak Katalin: Increasing the level of peroxisome proliferator-activated receptor γ coactivator-1α in podocytes results in collapsing glomerulopathy. JCI insight 2 (14): 2017.
Ko Yi-An, Yi Huiguang, Qiu Chengxiang, Huang Shizheng, Park Jihwan, Ledo Nora, Köttgen Anna, Li Hongzhe, Rader Daniel J, Pack Michael A, Brown Christopher D, Susztak Katalin: Genetic-Variation-Driven Gene-Expression Changes Highlight Genes with Important Functions for Kidney Disease. American journal of human genetics 100 (6): 940-953,2017.
Scerbo Diego, Son Ni-Huiping, Sirwi Alaa, Zeng Lixia, Sas Kelli M, Cifarelli Vincenza, Schoiswohl Gabriele, Huggins Lesley-Ann, Gumaste Namrata, Hu Yunying, Pennathur Subramaniam, Abumrad Nada A, Kershaw Erin E, Hussain M Mahmood, Susztak Katalin, Goldberg Ira J: Kidney triglyceride accumulation in the fasted mouse is dependent upon serum free fatty acids. Journal of lipid research 58 (6): 1132-1142,2017.
Beckerman Pazit, Bi-Karchin Jing, Park Ae Seo Deok, Qiu Chengxiang, Dummer Patrick D, Soomro Irfana, Boustany-Kari Carine M, Pullen Steven S, Miner Jeffrey H, Hu Chien-An A, Rohacs Tibor, Inoue Kazunori, Ishibe Shuta, Saleem Moin A, Palmer Matthew B, Cuervo Ana Maria, Kopp Jeffrey B, Susztak Katalin: Transgenic expression of human APOL1 risk variants in podocytes induces kidney disease in mice. Nature medicine 23 (4): 429-438,2017.
Kruse Michael, Fiallo Ariana, Tao Jianling, Susztak Katalin, Amann Kerstin, Katz Ellen B, Charron Maureen J: A High Fat Diet During Pregnancy and Lactation Induces Cardiac and Renal Abnormalities in GLUT4 +/- Male Mice. Kidney & blood pressure research 42 (3): 468-482,2017.
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