Penn/CHOP Immune Kidney Disease Collaboratory

Building a spatial single-cell atlas of healthy and diseased human kidneys to redefine immune-mediated kidney disease and identify precision diagnostic and therapeutic targets.
Completed Other B Cell Biology Biological & Mechanistic Biomarker Discovery Collaboration & Innovation Cross-institutional Collaboration Cytokine Signaling Disease Subtyping Experimental Platforms & Models Human Cohorts Single Cell Technologies Spatial Biology Therapeutic Development Translational & Clinical

Funding Year: 2024

Project Overview

Immune-mediated kidney diseases remain poorly understood at the cellular and systems level, limiting diagnostic precision and therapeutic development. In its first year, the Penn/CHOP Immune Kidney Disease Collaboratory established a prospective registry of over 320 biopsy-confirmed IgA nephropathy patients with matched clinical data, blood, and tissue. Using Xenium spatial transcriptomics, the team constructed the first single-cell spatial atlas of healthy and diseased human kidneys — spanning 1.7 million cells, 10 tissue niches, and 13 immune microenvironments. A novel B cell-rich microenvironment was identified that co-localizes with injured loop of Henle epithelium and expands threefold in chronic kidney disease. Multi-omics integration uncovered a 111-protein tubular injury/B cell biomarker panel whose top candidates predict progression to renal replacement therapy with HR > 2.5 in an external cohort of 2,986 individuals.

Impact & Innovation

The first spatial map of immune-mediated kidney disease.

 

By analyzing 1.7 million cells across healthy and diseased kidneys, this project identifies previously unrecognized B cell-rich and tubular injury microenvironments that predict kidney failure — and uncovers therapeutic targets including the BAFF/APRIL and PDGF-TGFβ signaling axes.

  • Discovers a B cell-predominant kidney microenvironment correlating with disease severity and progression risk, and identifies a 111-protein biomarker panel predicting renal replacement therapy in an external cohort of nearly 3,000 patients
  • Generates IP through a patent submission in progress for the Spatial Human Kidney Map, with an open-access registry, analytic tools, and atlas providing a scalable framework for immune-mediated renal disease research
  • Advances the Consortium’s Integrated Data and Discovery Platforms pillar by creating the first spatial single-cell kidney atlas as a shared, open-access resource accelerating discovery and therapeutic target validation across immune-mediated renal diseases
Research Approach

A framework designed for discovery

This project integrates a prospective clinical registry with single-cell spatial transcriptomics, proteogenomics, and multi-omics analysis to build a comprehensive cellular atlas of immune-mediated kidney disease and identify diagnostic biomarkers and therapeutic targets. The work combines large-scale patient cohort assembly with state-of-the-art molecular profiling platforms.

Xenium spatial transcriptomics applied to healthy and diseased kidney tissue from IgAN patients; single-cell analysis of 1.7 million cells spanning 10 tissue niches and 13 immune microenvironments; multi-omics integration to develop a 111-protein tubular injury/B cell biomarker panel; external cohort validation in 2,986 individuals for progression prediction; and BCR/TCR sequencing planned for Year 2.

Prospective registry of 320+ biopsy-confirmed IgAN patients with matched clinical data, blood, and biopsy tissue; single-cell spatial transcriptomic datasets from 1.7 million kidney cells; proteogenomic datasets for biomarker panel development; and external validation cohort of 2,986 individuals for renal replacement therapy progression analysis.

Identification of disease-associated kidney microenvironments, progression-predictive biomarker panels, and therapeutic targets — including the BAFF/APRIL and PDGF-TGFβ signaling axes — with translational goals including precision diagnostics for immune-mediated renal disease and an open-access atlas framework scalable across kidney disease research. A patent submission is in progress and a Nature manuscript is in revision.

Investigators & Institutions

Powering the science

Principal Investigator

Katalin Susztak, MD, PhD, Colton Consortium Member

Professor, Department of Medicine (Renal-Electrolyte and Hypertension), Perelman School of Medicine, University of Pennsylvania

Key Collaborators

Michelle Denburg, MD, MSCE

Attending Physician in the Division of Nephrology and the Cancer Survivorship Program at Children's Hospital of Philadelphia

Lawrence B. Holzman, MD

Professor of Medicine (Renal-Electrolyte and Hypertension), Perelman School of Medicine

Christopher A. Hunter, PhD

Mindy Halikman Heyer Distinguished Professor of Pathobiology, Perelman School of Medicine

Parker C. Wilson, MD, PhD

Assistant Professor of Pathology and Laboratory Medicine, Perelman School of Medicine

Colton Centers & Institutions

Colton Center for Autoimmunity at the University of Pennsylvania

Perelman School of Medicine

Children's Hospital of Philadelphia

Research Outputs

From insight to impact

Publications

Diabetes mellitus—progress and opportunities in the evolving epidemic

Cell
Abel, ED; Gloyn, AL; Evans-Molina, C; Joseph, JJ; Misra, S; Pajvani, UB; Simcox, J; Susztak, K; Drucker, DJ July 2024
Autoimmune EpidemiologyBiological & MechanisticEnvironmental ExposuresGene–Environment InteractionsHuman GeneticsImmunometabolismPopulation & Patient-CenteredTherapeutic DevelopmentTranslational & ClinicalEndocrine DiseasesType 1 DiabetesUniversity of Pennsylvania

Kidney multiome-based genetic scorecard reveals convergent coding and regulatory variants

Science
Liu, H; Abedini, A; Ha, E; Ma, Z; Sheng, X; Dumoulin, B; Qiu, C; Aranyi, T; Li, S; Dittrich, N; Chen, HC; Tao, R; Tarng, DC; Hsieh, FJ; Chen, SA; Yang, SF; Lee, MY; Kwok, PY; Wu, JY; Chen, CH; Khan, A; Limdi, NA; Wei, WQ; Walunas, TL; Karlson, EW; Kenny, EE; Luo, Y; Kottyan, L; Connolly, JJ; Jarvik, GP; Weng, C; Shang, N; Cole, JB; Mercader, JM; Mandla, R; Majarian, TD; Florez, JC; Haas, ME; Lotta, LA; Drivas, TG; Vy, HMT; Nadkarni, GN; Wiley, LK; Wilson, MP; Gignoux, CR; Rasheed, H; Thomas, LF; Åsvold, BO; Brumpton, BM; Hallan, SI; Hveem, K; Zheng, J; Hellwege, JN; Zawistowski, M; Zöllner, S; Franceschini, N; Hu, H; Zhou, J; Kiryluk, K; Ritchie, MD; Palmer, M; Edwards, TL; Voight, BF; Hung, AM; Susztak, K; Regeneron Genetics Center; GHS-RGC DiscovEHR Collaboration; Penn Medicine BioBank February 2025
BioinformaticsBiological & MechanisticData-Driven & QuantitativeDisease SubtypingExperimental Platforms & ModelsHuman CohortsHuman GeneticsMulti-omics IntegrationPrecision MedicineSingle Cell TechnologiesTranslational & ClinicalOtherUniversity of Pennsylvania

Spatial atlas of diabetic kidney disease reveals a B cell-rich subgroup

Nature
Dumoulin, B; Levinsohn, J; Klötzer, KA; Li, C; Mao, L; Ha, E; Mohandes, S; Nguyen, T; Paruzzo, L; Hirohama, D; Fang, V; Bhoj, VG; Parhiz, H; Andrade-Silva, M; Abedini, A; Bergeson, A; Traum, D; May, MJ; Kaestner, K; Ruella, M; McAllister, FE; Hakimi, AA; Li, M; Palmer, M; Wherry, EJ; Hunter, CA; Cancro, MP, TRIDENT Consortium; Susztak, K April 2026
Adaptive ImmunityB Cell BiologyBioinformaticsBiological & MechanisticBiomarker DiscoveryCytokine SignalingData-Driven & QuantitativeDisease SubtypingExperimental Platforms & ModelsHuman CohortsImmune ProfilingInnate ImmunityMulti-omics IntegrationSingle Cell TechnologiesSpatial BiologyTherapeutic DevelopmentTranslational & ClinicalEndocrine DiseasesOtherType 1 DiabetesUniversity of Pennsylvania

Additional Outputs

Publication in revision: Dumoulin B, et al. Spatial Human Kidney Map Highlights B Cell Driven Kidney Disease Subgroup. Nature, 2025.

Patent submission in progress: Spatial Human Kidney Map Highlights B Cell Driven Kidney Disease Subgroup.