Research interest: Work in my laboratory is aimed toward the understanding of molecular pathways that govern chronic kidney disease development.
Chronic kidney disease is an enormous burden on society. Our team aims to understand the genetics and molecular mechanism of kidney disease development, with the ultimate goal of finding new, more effective therapies.
We made discoveries fundamental towards defining critical genes, cell types and mechanisms of chronic kidney disease. Our studies were instrumental in defining genetic, epigenetic and transcriptional changes in diseased human kidneys. We identified multiple novel kidney disease genes and demonstrated role of Notch signaling and metabolic dysregulation in kidney disease development.
Our lab was the first to map the kidney epigenome and catalogue genotype-driven gene-expression variation (eQTL) in human kidneys. Integration of genome-wide association studies
(GWAS), eQTL and epigenome data has been essential to prioritize disease-causing genes and variants.
Our team generated the first unbiased, comprehensive kidney cell-type atlas using single cell transcriptomics. We identified that specific renal endophenotypes are linked and likely caused by the dysfunction of specific cell types.
In follow-up animal model studies, we conclusively demonstrated that MANBA, DAB2, CASP9, DPEP1/CHMP1A, DACH1 and APOL1 are new kidney disease risk genes. Her work established the role of proximal tubule cells, endolysosomal trafficking, metabolic and developmental pathways in kidney disease development.
Our discoveries span genetics, genomics, epigenetics, molecular biology, physiology and nephrology, and have enormous translational relevance and considerable therapeutic potential.
There are several; please speak with Dr. Susztak.
Hongbo Liu-postoctoral fellow
Poona Dhillon-postoctoral fellow
Ghazal Quinn-Instructor of Medicine
Hailong Hu-postoctoral fellow
Amin Abedini-postoctoral fellow
Dhanunjay Mukhi-postoctoral fellow
Jianfu Zhou-postoctoral fellow
Xiujie Liang-postoctoral fellow
Bibek Poudel-postoctoral fellow
Daigoro Hiroshima-postoctoral fellow
Shen Li-Visiting scientist
Andrea Sanchez-postoctoral fellow
Samer Mohandes-postoctoral fellow
Lakshmi Kolligunda-postoctoral fellow
Li Zeng-Visiting scientist
Konstantin Kloetzer -Student
Lauren Lee-graduate student
Mehrbod Vakhshoori-postoctoral fellow
Andi Bergeson- Research specialist
1. Niranjan T, Bielesz B, Gruenwald A, Ponda MP, Kopp JB, Thomas DB, Susztak K (2008)The Notch pathway in podocytes plays a role in the development of glomerular disease. Nat Med 14:290-8.
2. 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 (2015) Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development. Nat Med 21:37-46.
3. Beckerman P, Bi-Karchin J, Park AS, … Susztak K (2017) Transgenic expression of human APOL1 risk variants in podocytes induces kidney disease in mice. Nat Med 23:429-38.
4. Park J, Shrestha R, Qiu C, Kondo A, Huang S, Werth M, Li M, Barasch J, Susztak K (2018) Single-cell transcriptomics of the mouse kidney reveals potential cellular targets of kidney disease. Science 360:758-63.
5. Qiu C, Huang S, Park J, Park Y, Ko YA, Seasock MJ, Bryer JS, Xu XX, Song WC, Palmer M, Hill J, Guarnieri P, Hawkins J, Boustany-Kari CM, Pullen SS, Brown CD, Susztak K (2018) Renal compartment-specific genetic variation analyses identify new pathways in chronic kidney disease. Nat Med 24:1721-31.
6. Wu J, Ma Z, Raman A, … Susztak K (2021) APOL1 risk variants in individuals of African genetic ancestry drive endothelial cell defects that exacerbate sepsis. Immunity 54:2632-49 e6.
7. Wu J, Raman A, Coffey NJ, … Susztak K (2021) The key role of NLRP3 and STING in APOL1-associated podocytopathy. J Clin Invest 131(20):e136329.
8. Gu X, Yang H, Sheng X, … Susztak K (2021) Kidney disease genetic risk variants alter lysosomal beta-mannosidase (MANBA) expression and disease severity. Sci Transl Med 13(576):eaaz1458..
9. Doke T, Huang S, Qiu C, Liu H, Guan Y, Hu H, Ma Z, Wu J, Miao Z, Sheng X, Zhou J, Cao A, Li J, Kaufman L, Hung A, Brown CD, Pestell R, Susztak K (2021) Transcriptome-wide association analysis identifies DACH1 as a kidney disease risk gene that contributes to fibrosis. J Clin Invest 131(10):e141801.
10. Sheng X, Guan Y, Ma Z, Wu J, Liu H, Qiu C, Vitale S, Miao Z, Seasock MJ, Palmer M, Shin MK, Duffin KL, Pullen SS, Edwards TL, Hellwege JN, Hung AM, Li M, Voight BF, Coffman TM, Brown CD, Susztak K (2021) Mapping the genetic architecture of human traits to cell types in the kidney identifies mechanisms of disease and potential treatments. Nat Genet 53:1322-33.
Liang X, Aranyi T, Zhou J, Guan Y, Hu H, Liu H, Susztak K.: Tet2- and Tet3-Mediated Cytosine Hydroxymethylation in Six2 Progenitor Cells in Mice Is Critical for Nephron Progenitor Differentiation and Nephron Endowment. J Am Soc Nephrol Dec 2022.
Shao A, Gearhart MD, Chan SC, Miao Z, Susztak K, Igarashi P.: Multiomics analysis reveals that hepatocyte nuclear factor 1β regulates axon guidance genes in the developing mouse kidney. Sci Rep 12: 17586, Oct 2022.
Laster ML, Rowan B, Chen HC, Schwantes-An TH, Sheng X, Friedman PA, Ikizler TA, Sinshiemer JS, Ix JH, Susztak K, de Boer IH, Kestenbaum B, Hung A, Moe SM, Perwad F, Robinson-Cohen C.: Genetic Variants Associated With Mineral Metabolism Traits in Chronic Kidney Disease. J Clin Endocrinol Metab 107: e3866-e3876, Aug 2022.
Balzer MS, Doke T, Yang YW, Aldridge DL, Hu H, Mai H, Mukhi D, Ma Z, Shrestha R, Palmer MB, Hunter CA, Susztak K.: Single-cell analysis highlights differences in druggable pathways underlying adaptive or fibrotic kidney regeneration. Nat Commun 13: 4018, Jul 2022.
Liu H, Doke T, Guo D, Sheng X, Ma Z, Park J, Vy HMT, Nadkarni GN, Abedini A, Miao Z, Palmer M, Voight BF, Li H, Brown CD, Ritchie MD, Shu Y, Susztak K.: Epigenomic and transcriptomic analyses define core cell types, genes and targetable mechanisms for kidney disease. Nat Genet 2022.
Sandholm N, Cole JB, Nair V, Sheng X, Liu H, Ahlqvist E, van Zuydam N, Dahlström EH, Fermin D, Smyth LJ, Salem RM, Forsblom C, Valo E, Harjutsalo V, Brennan EP, McKay GJ, Andrews D, Doyle R, Looker HC, Nelson RG, Palmer C, McKnight AJ, Godson C, Maxwell AP, Groop L, McCarthy MI, Kretzler M, Susztak K, Hirschhorn JN, Florez JC, Groop PH; GENIE Consortium.: Genome-wide meta-analysis and omics integration identifies novel genes associated with diabetic kidney disease. Diabetologia 2022.
KDIGO Conference Participants.: Genetics in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int 2022.
Doke T, Susztak K.: The multifaceted role of kidney tubule mitochondrial dysfunction in kidney disease development. Trends Cell Biol 2022.
Chen TK, Surapaneni AL, Arking DE, Ballantyne CM, Boerwinkle E, Chen J, Coresh J, Köttgen A, Susztak K, Tin A, Yu B, Grams ME.: APOL1 Kidney Risk Variants and Proteomics. Clin J Am Soc Nephrol 2022.
Doke T, Abedini A, Aldridge DL, Yang YW, Park J, Hernandez CM, Balzer MS, Shrestra R, Coppock G, Rico JMI, Han SY, Kim J, Xin S, Piliponsky AM, Angelozzi M, Lefebvre V, Siracusa MC, Hunter CA, Susztak K.: Single-cell analysis identifies the interaction of altered renal tubules with basophils orchestrating kidney fibrosis. Nat Immunol 2022.
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Last updated: 12/17/2022
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