# Defining cellular mechanisms of chronic graft failure in transplanted hearts with single cell multi-omics

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2022 · $434,154

## Abstract

Project Summary/Abstract
Heart transplantation is a definitive treatment option for patients with end-stage heart failure. While short-term
survival has made substantial improvements, long-term outcomes are limited by chronic graft failure. Cardiac
allograft hypertrophy (CAH) is a clinical phenomenon referring to the gradual increase of left ventricular mass
and wall thickness of cardiac grafts. CAH onset can occur as early as 2 months after transplantation, which
often lead to progressive changes in cellular environment including cardiomyocytes hypertrophy and fibrosis
and accumulate to graft failure in long term. The complete landscape of cellular system in transplant patients
represents a major gap in knowledge. Single cell RNA sequencing (scRNA-seq) has emerged as powerful tool
to analyze diverse cell types and cell states as well as pseudo-time topologies of single cells in complex
organs, which however lacks the power to infer cell lineages that is important for identify the origins of
pathogenic cells. In this project, we will develop a novel single cell multi-omics sequencing technology and
several computational tools, which will enable simultaneous detection of cell lineage markers (i.e. DNAs) and
cell fate markers (i.e. RNAs) from same cells. We will also distinguish donor and host identities for all cells to
study their distinct roles in CAH that are largely unknown. We hypothesized that CAH is initiated by specific
immune cell subtypes and driven by endothelial to mesenchymal transition that is fueled by enlarged
cardiomyocytes. In aim 1, we will develop novel technology to define a unifying cell lineage and cell fate
roadmap for cardiac cells. Aim 2 will dissect temporal changes of cellular components in transplanted hearts
during CAH early onset. Aim 3 is to trace cell lineages during CAH progression with time-series single cell
multi-omics. Successful completion of this project will lead to the identification of donor and host originated cell
populations as novel therapeutic targets to extend the life of transplant patients.

## Key facts

- **NIH application ID:** 10334266
- **Project number:** 1R01HL160552-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Ruli Gao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $434,154
- **Award type:** 1
- **Project period:** 2022-04-20 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10334266

## Citation

> US National Institutes of Health, RePORTER application 10334266, Defining cellular mechanisms of chronic graft failure in transplanted hearts with single cell multi-omics (1R01HL160552-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10334266. Licensed CC0.

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