Information

Related Research Units

Nephrology Research

Research Overview

The goals of the Sampson lab are to map the genomic determinants of nephrotic syndrome through integrated system genomics and multiomic methods, and to discover the molecular, mechanistic, and clinical consequences of them when they are found. They are particularly interested in non-Mendelian strategies to map the genomic landscape of pediatric nephrotic syndrome. They use established methods from statistical genetics and population genetics to create high-quality variant call sets, perform genome-wide association and expression quantitative trait loci studies, and then contextualize disease-associated variants and transcripts with outcomes using genetic epidemiology approaches. In addition, when existing methods do not exist to answer important questions, they develop novel computational methods and bioinformatics tools. They are committed to creating user friendly, publicly available databases and web browsers of genomic information from kidney disease patients. To this end, they have publicly released patient genetic data at http://nephvs.org and eQTL and single-cell RNAseq data at http://nephqtl.org. Finally, they are committed to improving genomic literacy among Pediatric Nephrologists worldwide and maximizing the clinical utility of genomic testing in the clinic.

Research Background

Matt knew that he wanted to be a pediatrician since high school, but never imagined that once he became one, he'd be spending the majority of his time as a researcher, deeply engaged in improving the health of children with kidney disease through genomic discovery. He received his BS in Cell & Molecular Biology at Duke University and his MD at the University of Virginia. He spent the next six years at Children's Hospital of Philadelphia/University of Pennsylvania, where he completed his residency in Pediatrics, fellowship in Pediatric Nephrology, and a Master's Degree in Epidemiology-Human Genetics. After 8 years on Faculty at the University of Michigan, where he established his "kidneyomics" lab, he moved to Boston Children's Hospital in 2019 where he holds the Warren E. Grupe Chair in Pediatric Nephrology. He is also an Associate Member of the Broad Institute, where he is a member of the Kidney Disease Initiative. He is the co-chairman of the Genetics and Genomics Working Group of the Nephrotic Syndrome Study Network (NEPTUNE) and the Kidney Disease Working Group of the ClinGen Consortium. More information about Dr. Sampson's research can be found at http://sampsonlab.org and on his Twitter feed @kidneyomicsamps.

Education

Undergraduate School

Duke University
2000 Durham NC

Medical School

University of Virginia
2005 Charlottesville VA

Internship

Children's Hospital of Philadelphia
2006 Philadelphia PA

Residency

Children's Hospital of Philadelphia
2008 Philadelphia PA

Fellowship

Children's Hospital of Philadelphia
2011 Philadelphia PA

Graduate School

University of Pennsylvania
2011 Philadelphia PA

Publications

  1. The APOL1 p.N264K variant is co-inherited with the G2 kidney disease risk variant through a proximity recombination event. G3 (Bethesda). 2024 Dec 10. View Abstract
  2. Hospital-wide access to genomic data advanced pediatric rare disease research and clinical outcomes. NPJ Genom Med. 2024 Dec 02; 9(1):60. View Abstract
  3. Natural History and Clinicopathological Associations of TRPC6-Associated Podocytopathy. J Am Soc Nephrol. 2024 Oct 01. View Abstract
  4. Steroid-Resistant Nephrotic Syndrome Is Associated With a Unique Genetic Profile in a Highly Admixed Pediatric Population. Kidney Int Rep. 2024 Dec; 9(12):3501-3516. View Abstract
  5. Recessive variants in the intergenic NOS1AP-C1orf226 locus cause monogenic kidney disease responsive to anti-proteinuric treatment. medRxiv. 2024 Mar 21. View Abstract
  6. A Drosophila model to screen Alport syndrome COL4A5 variants for their functional pathogenicity. bioRxiv. 2024 Mar 11. View Abstract
  7. APOL1 Genotyping Is Incomplete without Testing for the Protective M1 Modifier p.N264K Variant. Glomerular Dis. 2024 Jan-Dec; 4(1):43-48. View Abstract
  8. Pediatric contributions and lessons learned from the NEPTUNE cohort study. Pediatr Nephrol. 2024 Sep; 39(9):2555-2568. View Abstract
  9. Idiopathic collapsing glomerulopathy is associated with APOL1 high-risk genotypes or Mendelian variants in most affected individuals in a highly admixed population. Kidney Int. 2024 Mar; 105(3):593-607. View Abstract
  10. Strong protective effect of the APOL1 p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease. Nat Commun. 2023 Nov 30; 14(1):7836. View Abstract
  11. The Significance of Hematuria in Podocytopathies. Clin J Am Soc Nephrol. 2024 Jan 01; 19(1):56-66. View Abstract
  12. Assessment of the Needs of Nephrology Divisions to Implement Return of Clinically Significant Research Genetic Results: A Survey of Nephrotic Syndrome Study Network (NEPTUNE) Investigators. Glomerular Dis. 2023 Jan-Dec; 3(1):178-188. View Abstract
  13. Strong protective effect of the APOL1 p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease. medRxiv. 2023 Aug 04. View Abstract
  14. The association of low birthweight and prematurity on outcomes in children and adults with nephrotic syndrome-a NEPTUNE cohort study. Pediatr Nephrol. 2023 10; 38(10):3297-3308. View Abstract
  15. Multi-population genome-wide association study implicates immune and non-immune factors in pediatric steroid-sensitive nephrotic syndrome. Nat Commun. 2023 04 29; 14(1):2481. View Abstract
  16. Mapping genomic regulation of kidney disease and traits through high-resolution and interpretable eQTLs. Nat Commun. 2023 04 19; 14(1):2229. View Abstract
  17. Quality assessment and refinement of chromatin accessibility data using a sequence-based predictive model. Proc Natl Acad Sci U S A. 2022 12 20; 119(51):e2212810119. View Abstract
  18. ADAR regulates APOL1 via A-to-I RNA editing by inhibition of MDA5 activation in a paradoxical biological circuit. Proc Natl Acad Sci U S A. 2022 11; 119(44):e2210150119. View Abstract
  19. Comparing Kidney Health Outcomes in Children, Adolescents, and Adults With Focal Segmental Glomerulosclerosis. JAMA Netw Open. 2022 08 01; 5(8):e2228701. View Abstract
  20. Analyzing and reconciling colocalization and transcriptome-wide association studies from the perspective of inferential reproducibility. Am J Hum Genet. 2022 05 05; 109(5):825-837. View Abstract
  21. A glomerular transcriptomic landscape of apolipoprotein L1 in Black patients with focal segmental glomerulosclerosis. Kidney Int. 2022 07; 102(1):136-148. View Abstract
  22. Discovery of Autoantibodies Targeting Nephrin in Minimal Change Disease Supports a Novel Autoimmune Etiology. J Am Soc Nephrol. 2022 01; 33(1):238-252. View Abstract
  23. Uncovering genetic mechanisms of hypertension through multi-omic analysis of the kidney. Nat Genet. 2021 05; 53(5):630-637. View Abstract
  24. A Rare Autosomal Dominant Variant in Regulator of Calcineurin Type 1 (RCAN1) Gene Confers Enhanced Calcineurin Activity and May Cause FSGS. J Am Soc Nephrol. 2021 Jul; 32(7):1682-1695. View Abstract
  25. APOL1 at 10 years: progress and next steps. Kidney Int. 2021 06; 99(6):1296-1302. View Abstract
  26. APOL1 genotype-associated morphologic changes among patients with focal segmental glomerulosclerosis. Pediatr Nephrol. 2021 09; 36(9):2747-2757. View Abstract
  27. Copy Number Variant Analysis and Genome-wide Association Study Identify Loci with Large Effect for Vesicoureteral Reflux. J Am Soc Nephrol. 2021 Apr; 32(4):805-820. View Abstract
  28. APOL1 in an ethnically diverse pediatric population with nephrotic syndrome: implications in focal segmental glomerulosclerosis and other diagnoses. Pediatr Nephrol. 2021 08; 36(8):2327-2336. View Abstract
  29. Diagnoses of uncertain significance: kidney genetics in the 21st century. Nat Rev Nephrol. 2020 11; 16(11):616-618. View Abstract
  30. Quantify and control reproducibility in high-throughput experiments. Nat Methods. 2020 12; 17(12):1207-1213. View Abstract
  31. Common risk variants in NPHS1 and TNFSF15 are associated with childhood steroid-sensitive nephrotic syndrome. Kidney Int. 2020 11; 98(5):1308-1322. View Abstract
  32. The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis. Nat Commun. 2020 03 30; 11(1):1600. View Abstract
  33. Introduction to Genomics of Kidney Disease: Implications, Discovery, and Translation. Clin J Am Soc Nephrol. 2020 02 07; 15(2):267. View Abstract
  34. Urinary Epidermal Growth Factor as a Marker of Disease Progression in Children With Nephrotic Syndrome. Kidney Int Rep. 2020 Apr; 5(4):414-425. View Abstract
  35. Brazilian Network of Pediatric Nephrotic Syndrome (REBRASNI). Kidney Int Rep. 2020 Mar; 5(3):358-362. View Abstract
  36. Author Correction: Using and producing publicly available genomic data to accelerate discovery in nephrology. Nat Rev Nephrol. 2019 Sep; 15(9):590. View Abstract
  37. Using and producing publicly available genomic data to accelerate discovery in nephrology. Nat Rev Nephrol. 2019 09; 15(9):523-524. View Abstract
  38. Unique association of multiple endocrine neoplasia 2A and congenital anomalies of the kidney and urinary tract in a child with a RET mutation. BMJ Case Rep. 2019 Aug 30; 12(8). View Abstract
  39. Effect of parental origin of damaging variants in pro-angiogenic genes on fetal growth in patients with congenital heart defects: Data and analyses. Data Brief. 2019 Aug; 25:104311. View Abstract
  40. Damaging Variants in Proangiogenic Genes Impair Growth in Fetuses with Cardiac Defects. J Pediatr. 2019 10; 213:103-109. View Abstract
  41. The human nephrin Y1139RSL motif is essential for podocyte foot process organization and slit diaphragm formation during glomerular development. J Biol Chem. 2019 07 12; 294(28):10773-10788. View Abstract
  42. Genomic Mismatch at LIMS1 Locus and Kidney Allograft Rejection. N Engl J Med. 2019 05 16; 380(20):1918-1928. View Abstract
  43. Disruption of the exocyst induces podocyte loss and dysfunction. J Biol Chem. 2019 06 28; 294(26):10104-10119. View Abstract
  44. Sex-specific and pleiotropic effects underlying kidney function identified from GWAS meta-analysis. Nat Commun. 2019 04 23; 10(1):1847. View Abstract
  45. Genetics of Nephrotic Syndrome Presenting in Childhood: Core Curriculum 2019. Am J Kidney Dis. 2019 10; 74(4):549-557. View Abstract
  46. Author Correction: The copy number variation landscape of congenital anomalies of the kidney and urinary tract. Nat Genet. 2019 04; 51(4):764. View Abstract
  47. Integrated Functional Genomic Analysis Enables Annotation of Kidney Genome-Wide Association Study Loci. J Am Soc Nephrol. 2019 Mar; 30(3):421-441. View Abstract
  48. Glomerular and tubulointerstitial eQTLs for genomic discovery. Nat Rev Nephrol. 2019 01; 15(1):3-4. View Abstract
  49. The copy number variation landscape of congenital anomalies of the kidney and urinary tract. Nat Genet. 2019 01; 51(1):117-127. View Abstract
  50. An eQTL Landscape of Kidney Tissue in Human Nephrotic Syndrome. Am J Hum Genet. 2018 08 02; 103(2):232-244. View Abstract
  51. Transethnic, Genome-Wide Analysis Reveals Immune-Related Risk Alleles and Phenotypic Correlates in Pediatric Steroid-Sensitive Nephrotic Syndrome. J Am Soc Nephrol. 2018 07; 29(7):2000-2013. View Abstract
  52. UBD modifies APOL1-induced kidney disease risk. Proc Natl Acad Sci U S A. 2018 03 27; 115(13):3446-3451. View Abstract
  53. A null variant in the apolipoprotein L3 gene is associated with non-diabetic nephropathy. Nephrol Dial Transplant. 2018 02 01; 33(2):323-330. View Abstract
  54. The Democratization of Genomic Inquiry Empowers Our Understanding of Nephrotic Syndrome. Transplantation. 2017 12; 101(12):2814-2815. View Abstract
  55. An investigation of APOL1 risk genotypes and preterm birth in African American population cohorts. Nephrol Dial Transplant. 2017 Dec 01; 32(12):2051-2058. View Abstract
  56. Exome-wide Association Study Identifies GREB1L Mutations in Congenital Kidney Malformations. Am J Hum Genet. 2017 Nov 02; 101(5):789-802. View Abstract
  57. Erratum to: Evaluating Mendelian nephrotic syndrome genes for evidence for risk alleles or oligogenicity that explain heritability. Pediatr Nephrol. 2017 07; 32(7):1285. View Abstract
  58. APOL1-associated glomerular disease among African-American children: a collaboration of the Chronic Kidney Disease in Children (CKiD) and Nephrotic Syndrome Study Network (NEPTUNE) cohorts. Nephrol Dial Transplant. 2017 Jun 01; 32(6):983-990. View Abstract
  59. The Phenotypic Spectrum of Nephropathies Associated with Mutations in Diacylglycerol Kinase e. J Am Soc Nephrol. 2017 10; 28(10):3066-3075. View Abstract
  60. A Case of Hyperphosphatemia and Elevated Fibroblast Growth Factor 23: A Brief Review of Hyperphosphatemia and Fibroblast Growth Factor 23 Pathway. Kidney Int Rep. 2017 Nov; 2(6):1238-1242. View Abstract
  61. Genetic Drivers of Kidney Defects in the DiGeorge Syndrome. N Engl J Med. 2017 02 23; 376(8):742-754. View Abstract
  62. Renal and Cardiovascular Morbidities Associated with APOL1 Status among African-American and Non-African-American Children with Focal Segmental Glomerulosclerosis. Front Pediatr. 2016; 4:122. View Abstract
  63. Evaluating Mendelian nephrotic syndrome genes for evidence for risk alleles or oligogenicity that explain heritability. Pediatr Nephrol. 2017 03; 32(3):467-476. View Abstract
  64. A Familial Infantile Renal Failure. Kidney Int Rep. 2017 Mar; 2(2):130-133. View Abstract
  65. A reference panel of 64,976 haplotypes for genotype imputation. Nat Genet. 2016 10; 48(10):1279-83. View Abstract
  66. tarSVM: Improving the accuracy of variant calls derived from microfluidic PCR-based targeted next generation sequencing using a support vector machine. BMC Bioinformatics. 2016 Jun 10; 17(1):233. View Abstract
  67. A role for genetic susceptibility in sporadic focal segmental glomerulosclerosis. J Clin Invest. 2016 Apr 01; 126(4):1603. View Abstract
  68. A role for genetic susceptibility in sporadic focal segmental glomerulosclerosis. J Clin Invest. 2016 Mar 01; 126(3):1067-78. View Abstract
  69. Complete Remission in the Nephrotic Syndrome Study Network. Clin J Am Soc Nephrol. 2016 Jan 07; 11(1):81-9. View Abstract
  70. Tissue transcriptome-driven identification of epidermal growth factor as a chronic kidney disease biomarker. Sci Transl Med. 2015 Dec 02; 7(316):316ra193. View Abstract
  71. Using Population Genetics to Interrogate the Monogenic Nephrotic Syndrome Diagnosis in a Case Cohort. J Am Soc Nephrol. 2016 07; 27(7):1970-83. View Abstract
  72. Actualizing the Benefits of Genomic Discovery in Pediatric Nephrology. J Pediatr Genet. 2016 Mar; 5(1):69-75. View Abstract
  73. GeneVetter: a web tool for quantitative monogenic assessment of rare diseases. Bioinformatics. 2015 Nov 15; 31(22):3682-4. View Abstract
  74. Integrative Genomics Identifies Novel Associations with APOL1 Risk Genotypes in Black NEPTUNE Subjects. J Am Soc Nephrol. 2016 Mar; 27(3):814-23. View Abstract
  75. Whole Exome Sequencing Reveals Novel PHEX Splice Site Mutations in Patients with Hypophosphatemic Rickets. PLoS One. 2015; 10(6):e0130729. View Abstract
  76. Opportunities and Challenges of Genotyping Patients With Nephrotic Syndrome in the Genomic Era. Semin Nephrol. 2015 May; 35(3):212-21. View Abstract
  77. Defining nephrotic syndrome from an integrative genomics perspective. Pediatr Nephrol. 2015 Jan; 30(1):51-63; quiz 59. View Abstract
  78. A chiral HPLC-MS/MS method for simultaneous quantification of warfarin enantiomers and its major hydroxylation metabolites of CYP2C9 and CYP3A4 in human plasma. Austin J Anal Pharm Chem. 2014; 1(2). View Abstract
  79. Gene-level integrated metric of negative selection (GIMS) prioritizes candidate genes for nephrotic syndrome. PLoS One. 2013; 8(11):e81062. View Abstract
  80. Design of the Nephrotic Syndrome Study Network (NEPTUNE) to evaluate primary glomerular nephropathy by a multidisciplinary approach. Kidney Int. 2013 Apr; 83(4):749-56. View Abstract
  81. Genes, Exomes, Genomes, Copy Number: What is Their Future in Pediatric Renal Disease. Curr Pediatr Rep. 2013 Mar; 1(1):52-59. View Abstract
  82. Copy-number disorders are a common cause of congenital kidney malformations. Am J Hum Genet. 2012 Dec 07; 91(6):987-97. View Abstract
  83. Evidence for a recurrent microdeletion at chromosome 16p11.2 associated with congenital anomalies of the kidney and urinary tract (CAKUT) and Hirschsprung disease. Am J Med Genet A. 2010 Oct; 152A(10):2618-22. View Abstract
  84. A genomewide scan for loci predisposing to type 2 diabetes in a U.K. population (the Diabetes UK Warren 2 Repository): analysis of 573 pedigrees provides independent replication of a susceptibility locus on chromosome 1q. Am J Hum Genet. 2001 Sep; 69(3):553-69. View Abstract
  85. Appropriate insulin regimes for type 2 diabetes: a multicenter randomized crossover study. Diabetes Care. 2000 Nov; 23(11):1612-8. View Abstract
  86. Assessment of monoethylglycinexylidide as measure of liver function for patients with chronic viral hepatitis. Clin Chem. 1997 Oct; 43(10):1952-7. View Abstract

Contact Matthew Sampson

Phone: 617-919-7689
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