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Katalin Susztak

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Katalin Susztak
Born
NationalityHungarian-American
Alma materSemmelweis University, Albert Einstein College of Medicine
OccupationNephrologist

Katalin Susztak (Suszták) is a Hungarian American scientist and nephrologist at the Perelman School of Medicine at the University of Pennsylvania. She is a professor of medicine and genetics, and currently the codirector of the Complications Unit at the Institute for Diabetes, Obesity and Metabolism. Her laboratory made major contributions to the current understanding of kidney disease development.[1][2][3][4][5][6][7][8][9][10] She is also the founder of the Transformative Research In DiabEtic NephropaThy (TRIDENT),[11] a collaborative network of physicians and basic scientists, to find cures for diabetic kidney disease.

Early life and education

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Susztak was born in Eger, Hungary.[12] She attended the Apáczai Csere János High School, a magnet school in Budapest Hungary. She obtained her MD (1995), and PhD (1997) degrees with Summa Cum Laude from the Semmelweis University, in Budapest Hungary.[13] She moved to the United States in 1997, where she completed an Internal Medicine residency (2000) and Nephrology fellowship (2003) at the Albert Einstein College of Medicine in New York. She also obtained a Master of Science in Clinical Research (M.S.) (2004) with distinction from Einstein College.[13] She is Board certified in Internal Medicine (2000) and Nephrology (2002).

Career

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Susztak was faculty at the Albert Einstein College of Medicine as an Instructor (2003-2004), Assistant Professor (2004-2009) and as an Associate Professor (2009-2012). In 2012 she moved to the Perelman School of Medicine of the University of Pennsylvania as a tenured Associate Professor of Medicine. In 2017 she became a Professor of Medicine and Professor of Genetics at the Perelman School of Medicine of the University of Pennsylvania.[14] In 2018 she became the Director of Complications Unit at the Institute of Diabetes and Metabolism.[15] In 2016, she founded the TRIDENT consortium, a collaborative network of physicians and basic scientists, to find cures for diabetic kidney disease.[16]

Scientific contributions

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Susztak has made important discoveries towards defining critical genes, cell types and mechanisms of chronic kidney disease. She published over 160 scientific articles. Her early work demonstrated the importance of podocyte apoptosis in diabetic kidney disease development.[1] She was instrumental in defining genetic, epigenetic and transcriptional changes in diseased human kidneys.[3][4][8][17][18] She identified novel kidney disease genes and demonstrated the contribution of the Notch signaling pathway[2] and metabolic dysregulation[4] to kidney disease development.

Susztak's laboratory generated the first unbiased, comprehensive kidney cell-type atlas using single cell transcriptomics. She identified that specific renal phenotypes are linked and likely caused by the dysfunction of specific cell types.[6][9]

Her lab was the first to map the kidney epigenome and catalogue genotype-driven gene-expression variation (Expression quantitative trait loci; eQTL) in human kidneys.[3][7] Integration of genome wide association (GWAS), eQTL and epigenome data has been essential to prioritize disease-causing genes and variants.

In follow-up animal model studies her laboratory conclusively demonstrated that the lysosomal beta-mannosidase,[18] the adaptor protein DAB2,[7] and Dachshund homolog 1 (DACH1) are important kidney disease risk genes. Her work established the role of proximal tubule cells,[7][9] endolysosomal trafficking,[5][18] metabolic[4] and developmental pathways[2] in kidney disease development. Furthermore, her group generated the first animal model and showed that genetic variants in Apolipoprotein L1 (APOL1)[5] observed only in African American Americans cause kidney disease development.

Susztak's discoveries span genetics, genomics, epigenetics, molecular biology, physiology and nephrology, and have important translational relevance and considerable therapeutic potential.

Awards

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References

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  1. ^ a b Susztak, Katalin; Raff, Amanda C.; Schiffer, Mario; Böttinger, Erwin P. (January 2006). "Glucose-induced reactive oxygen species cause apoptosis of podocytes and podocyte depletion at the onset of diabetic nephropathy". Diabetes. 55 (1): 225–233. doi:10.2337/diabetes.55.01.06.db05-0894. ISSN 0012-1797. PMID 16380497.
  2. ^ a b c Niranjan, Thiruvur; Bielesz, Bernhard; Gruenwald, Antje; Ponda, Manish P.; Kopp, Jeffrey B.; Thomas, David B.; Susztak, Katalin (March 2008). "The Notch pathway in podocytes plays a role in the development of glomerular disease". Nature Medicine. 14 (3): 290–298. doi:10.1038/nm1731. ISSN 1546-170X. PMID 18311147. S2CID 29990985.
  3. ^ a b c Ko, Yi-An; Mohtat, Davoud; Suzuki, Masako; Park, Ae Seo Deok; Izquierdo, Maria Concepcion; Han, Sang Youb; Kang, Hyun Mi; Si, Han; Hostetter, Thomas; Pullman, James M.; Fazzari, Melissa (2013). "Cytosine methylation changes in enhancer regions of core pro-fibrotic genes characterize kidney fibrosis development". Genome Biology. 14 (10): R108. doi:10.1186/gb-2013-14-10-r108. ISSN 1474-760X. PMC 4053753. PMID 24098934.
  4. ^ a b c d Kang, Hyun Mi; Ahn, Seon Ho; Choi, Peter; Ko, Yi-An; Han, Seung Hyeok; Chinga, Frank; Park, Ae Seo Deok; Tao, Jianling; Sharma, Kumar; Pullman, James; Bottinger, Erwin P. (January 2015). "Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development". Nature Medicine. 21 (1): 37–46. doi:10.1038/nm.3762. ISSN 1546-170X. PMC 4444078. PMID 25419705.
  5. ^ a b c 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 (April 2017). "Transgenic expression of human APOL1 risk variants in podocytes induces kidney disease in mice". Nature Medicine. 23 (4): 429–438. doi:10.1038/nm.4287. ISSN 1546-170X. PMC 5603285. PMID 28218918.
  6. ^ a b Park, Jihwan; Shrestha, Rojesh; Qiu, Chengxiang; Kondo, Ayano; Huang, Shizheng; Werth, Max; Li, Mingyao; Barasch, Jonathan; Suszták, Katalin (2018-05-18). "Single-cell transcriptomics of the mouse kidney reveals potential cellular targets of kidney disease". Science. 360 (6390): 758–763. doi:10.1126/science.aar2131. ISSN 1095-9203. PMC 6188645. PMID 29622724.
  7. ^ a b c d 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 (November 2018). "Renal compartment-specific genetic variation analyses identify new pathways in chronic kidney disease". Nature Medicine. 24 (11): 1721–1731. doi:10.1038/s41591-018-0194-4. ISSN 1546-170X. PMC 6301011. PMID 30275566.
  8. ^ a b Chung, Ki Wung; Dhillon, Poonam; Huang, Shizheng; Sheng, Xin; Shrestha, Rojesh; Qiu, Chengxiang; Kaufman, Brett A.; Park, Jihwan; Pei, Liming; Baur, Joseph; Palmer, Matthew (2019-10-01). "Mitochondrial Damage and Activation of the STING Pathway Lead to Renal Inflammation and Fibrosis". Cell Metabolism. 30 (4): 784–799.e5. doi:10.1016/j.cmet.2019.08.003. ISSN 1932-7420. PMC 7054893. PMID 31474566.
  9. ^ a b c Dhillon, Poonam; Park, Jihwan; Hurtado Del Pozo, Carmen; Li, Lingzhi; Doke, Tomohito; Huang, Shizheng; Zhao, Juanjuan; Kang, Hyun Mi; Shrestra, Rojesh; Balzer, Michael S.; Chatterjee, Shatakshee (2021-02-02). "The Nuclear Receptor ESRRA Protects from Kidney Disease by Coupling Metabolism and Differentiation". Cell Metabolism. 33 (2): 379–394.e8. doi:10.1016/j.cmet.2020.11.011. ISSN 1932-7420. PMC 9259369. PMID 33301705. S2CID 228100288.
  10. ^ Sheng, Xin; Qiu, Chengxiang; Liu, Hongbo; Gluck, Caroline; Hsu, Jesse Y.; He, Jiang; Hsu, Chi-Yuan; Sha, Daohang; Weir, Matthew R.; Isakova, Tamara; Raj, Dominic (2020-11-17). "Systematic integrated analysis of genetic and epigenetic variation in diabetic kidney disease". Proceedings of the National Academy of Sciences of the United States of America. 117 (46): 29013–29024. Bibcode:2020PNAS..11729013S. doi:10.1073/pnas.2005905117. ISSN 1091-6490. PMC 7682409. PMID 33144501.
  11. ^ "TRIDENT - University of Pennsylvania".
  12. ^ Susztak, K.; Cifra, A. (2014). "Back and forth' from models to patients to understand kidney disease: an interview with Katalin Susztak". Disease Models & Mechanisms. 7 (12). The Company of Biologist: 1317–1319. doi:10.1242/dmm.018911. PMC 4257000. PMID 25481011. Retrieved 2021-06-29.
  13. ^ a b "University of Pennsylvania Katalin Susztak Faculty page".
  14. ^ "Katalin Susztak Faculty Webpage, Department of Medicine, University of Pennsylvania".
  15. ^ "Complications Unit, Institute for Diabetes, Obesity and Metabolism".
  16. ^ Townsend, Raymond R.; Guarnieri, Paolo; Argyropoulos, Christos; Blady, Shira; Boustany-Kari, Carine M.; Devalaraja-Narashimha, Kishor; Morton, Lori; Mottl, Amy K.; Patel, Uptal; Palmer, Matthew; Ross, Michael J. (January 2020). "Rationale and design of the Transformative Research in Diabetic Nephropathy (TRIDENT) Study". Kidney International. 97 (1): 10–13. doi:10.1016/j.kint.2019.09.020. ISSN 1523-1755. PMID 31901339. S2CID 209893446.
  17. ^ Gluck, Caroline; Qiu, Chengxiang; Han, Sang Youb; Palmer, Matthew; Park, Jihwan; Ko, Yi-An; Guan, Yuting; Sheng, Xin; Hanson, Robert L.; Huang, Jing; Chen, Yong (2019-06-05). "Kidney cytosine methylation changes improve renal function decline estimation in patients with diabetic kidney disease". Nature Communications. 10 (1): 2461. Bibcode:2019NatCo..10.2461G. doi:10.1038/s41467-019-10378-8. ISSN 2041-1723. PMC 6549146. PMID 31165727.
  18. ^ a b c 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. (2017-06-01). "Genetic-Variation-Driven Gene-Expression Changes Highlight Genes with Important Functions for Kidney Disease". American Journal of Human Genetics. 100 (6): 940–953. doi:10.1016/j.ajhg.2017.05.004. ISSN 1537-6605. PMC 5473735. PMID 28575649.
  19. ^ "Elected Members of the American Society for Clinical Investigation 2011".
  20. ^ "Recipients of the Donald W Seldin Young Investigator Award".
  21. ^ "Alfred Newton Richards Award 2021". 6 April 2021.
  22. ^ "2021 Awards of Excellence Recipients".