# Single Cell Analysis of Kidney Transplant Antibody Mediated Rejection

> **NIH NIH K08** · WASHINGTON UNIVERSITY · 2020 · $164,258

## Abstract

PROJECT SUMMARY/ABSTRACT
Kidney transplantation offers the greatest survival advantage to patients with end stage kidney disease and is
vastly more cost effective than dialysis. Long-term survival of kidney transplants has not improved in recent
decades. Antibody mediated rejection (AMR) has been identified as a major cause of transplant failure. Currently,
management of patients with AMR is inconsistent among centers and frequently fails. We hypothesize that the
cell types and cell states unique to AMR can be resolved by single cell RNA sequencing (scRNA-seq) of biopsy
samples taken from patients at the time of diagnosis. This approach uses an unsupervised framework for
dissecting transcriptional heterogeneity within complex tissues such as the kidney. This allows for the
interrogation of cell states and subpopulations using an unbiased clustering approach that is independent of
previous knowledge and can provide unprecedented resolution. To test our hypothesis we propose the following
aims: In Aim 1, we will perform scRNA-seq of 40 research biopsy cores (20 AMR and 20 non-AMR). From this
data we will identify genes expressed in endothelial cells and antibody secreting cells that define AMR specific
phenotypes. We have demonstrated feasibility of this approach by generating single cell data from human biopsy
samples as outlined in the research plan. For Aim 2, we will use immunohistochemistry to validate these AMR
specific markers on a set of independent tissue samples. For Aim 3, we will use publicly available Affymetrix
microarray datasets from kidney transplant biopsies with associated outcomes data to determine which cell types
are associated with allograft outcome. This proposal logically builds on the principal investigator’s previous
research experience and clinical training. To date he has been working full time in clinical transplantation and
continuing his research endeavors on an ‘out of hours’ basis. Despite this his research output and experience
continue to grow and he has recently published a report on the first successful application of this technology to
human kidney biopsy tissue (co-first author). This proposal now focuses on expanding his scientific skills by
attaining additional knowledge and practical research experience in single cell methods, bioinformatics and
immunology. The career development goals will be achieved through a multi-faceted approach involving
mentoring by Dr. Benjamin Humphreys and an advisory committee consisting of Drs. Barbara Murphy (transplant
genomics), Phil Payne (biomedical informatics and translational science), Rob Mitra (single cell applications)
and Paul Allen (translational immunology), didactic coursework, scientific investigation, and training in scientific
communication and research ethics. This work will take place in Washington University which has a rich history
of mentoring successful physician-scientists. Successful completion of this career development award will result
in a better ...

## Key facts

- **NIH application ID:** 9908076
- **Project number:** 5K08DK120953-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** ANDREW FRANCIS MALONE
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $164,258
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9908076

## Citation

> US National Institutes of Health, RePORTER application 9908076, Single Cell Analysis of Kidney Transplant Antibody Mediated Rejection (5K08DK120953-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9908076. Licensed CC0.

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