Description of Research Expertise
Research interest: Work in my laboratory is aimed toward the understanding of molecular pathways that govern chronic kidney disease development.
Research details
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.
Rotation Projects
There are several; please speak with Dr. Susztak.
Lab Personnel:
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
Yu Yan-Student
Lakshmi Kolligunda-postoctoral fellow
Jonathan Levinsohn
Li Zeng-Visiting scientist
Konstantin Kloetzer -Student
Lauren Lee-graduate student
Mehrbod Vakhshoori-postoctoral fellow
Andi Bergeson- Research specialist
Selected Publications:
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.
Selected Publications
Deshpande RS, Langham MC, Susztak K, Wehrli FW.: MRI-based quantification of whole-organ renal metabolic rate of oxygen NMR Biomed : 2024.
Mukhi D, Li L, Liu H, Doke T, Kolligundla LP, Ha E, Klötzer KA, Abedini A, Mukherjee S, Wu J, Dhillon P, Hu H, Guan D, Funai K, Uehara K, Titchenell PM, Baur JA, Wellen KE, Susztak K.: ACSS2 gene variants determine kidney disease risk by controlling de novo lipogenesis in kidney tubules J Clin Invest : 2023.
Latt KZ, Yoshida T, Shrivastav S, Abedini A, Reece JM, Sun Z, Lee H, Okamoto K, Dagur P, Heymann J, Zhao Y, Chung JY, Hewitt S, Jose PA, Lee K, He JC, Winkler CA, Knepper MA, Kino T, Rosenberg AZ, Susztak K, Kopp JB.: HIV viral protein R induces loss of DCT1-type renal tubules bioRxiv : 2023.
Zhou J, Abedini A, Balzer MS, Shrestha R, Dhillon P, Liu H, Hu H, Susztak K.: Unified Mouse and Human Kidney Single-Cell Expression Atlas Reveal Commonalities and Differences in Disease States J Am Soc Nephrol 34 : 1843-1862,2023.
Hung AM, Assimon VA, Chen HC, Yu Z, Vlasschaert C, Triozzi JL, Chan H, Wheless L, Wilson O, Shah SC, Mack T, Thompson T, Matheny ME, Chandrasekar S, Mozaffari SV, Chung CP, Tsao P, Susztak K, Siew ED, Estrada K, Gaziano JM, Graham RR, Tao R, Hoek M, Robinson-Cohen C, Green EM, Bick AG; Million Veteran Program.: Genetic Inhibition of APOL1 Pore-Forming Function Prevents APOL1-Mediated Kidney Disease J Am Soc Nephrol 34 : 1889-1899,2023.
Levinsohn J, Li S, Ha E, Susztak K.: Combing Genome-Wide Association Studies and Single-Cell Analysis to Elucidate the Mechanisms of Kidney Disease: Proceedings of the Henry Shavelle Professorship Glomerular Dis 3 : 258-265,2023.
Onodera T, Wang MY, Rutkowski JM, Deja S, Chen S, Balzer MS, Kim DS, Sun X, An YA, Field BC, Lee C, Matsuo EI, Mizerska M, Sanjana I, Fujiwara N, Kusminski CM, Gordillo R, Gautron L, Marciano DK, Hu MC, Burgess SC, Susztak K, Moe OW, Scherer PE.: Endogenous renal adiponectin drives gluconeogenesis through enhancing pyruvate and fatty acid utilization Nat Commun 14 : 6531,2023.
Abedini A, Sanchez-Navarro A, Wu J, Klötzer KA, Ma Z, Poudel B, Doke T, Balzer MS, Frederick J, Cernecka H, Liu H, Liang X, Vitale S, Kolkhof P, Susztak K.: Single-cell transcriptomics and chromatin accessibility profiling elucidate the kidney protective mechanism of mineralocorticoid receptor antagonists J Clin Invest : 2023.
Zhang Z, Mathew D, Lim T, Mason K, Martinez CM, Huang S, Wherry EJ, Susztak K, Minn AJ, Ma Z, Zhang NR.: Signal recovery in single cell batch integration bioRxiv : 2023.
Hirohama D, Abedini A, Moon S, Surapaneni A, Dillon ST, Vassalotti A, Liu H, Doke T, Martinez V, Md Dom Z, Karihaloo A, Palmer MB, Coresh J, Grams ME, Niewczas MA, Susztak K.: Unbiased Human Kidney Tissue Proteomics Identifies Matrix Metalloproteinase 7 as a Kidney Disease Biomarker J Am Soc Nephrol 34 : 1279-1291,2023.
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Academic Contact Information
12-123 Smilow Center for Translational Research
3400 Civic Center Blvd
Philadelphia,
PA
19104
Phone: 215-898-2009