# Pre-Transplant Multiomic Profiling to Quantify The Risk of Rejection Following Heart Transplantation

> **NIH NIH K23** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $185,579

## Abstract

PROJECT SUMMARY______________________________________________________________________
One-third of heart transplant recipients will develop acute rejection of their new heart within the first post-
transplant year. These episodes can cause worsening heart failure, acceleration of chronic rejection, and
decrease post-transplant survival. Although immunosuppression decreases the risk of rejection, its long-term
use is associated with infection, cancer, and worsening kidney disease, all of which may limit the lifespan of a
patient after transplant. The ability to safely minimize immunosuppression without increasing the risk of
rejection would improve heart transplant recipients' outcomes. Calculating the risk of rejection for a given
patient remains a clinical challenge, as age, sex, and immunologic mismatch between the donor and recipient
are incomplete predictors of risk. While several non-invasive tests are available to diagnose rejection after
transplant, there is not currently an assay that can be used before transplant to quantify whether a recipient is
more prone to infection or rejection. If we could identify heart transplant candidates at low risk for rejection, we
could safely minimize immunosuppression and its toxicities without increasing the risk of graft loss. The
objective of the proposed study is to leverage a large, well-phenotyped cohort with existing biospecimens and
multi-omic technologies to identify novel pre-transplant biomarkers associated with clinically significant
rejection within the first post-transplant year. First, we will perform proteomic profiling to validate three
biomarkers (FGF-2, SPRTY-2, IRAK-1) we identified in preliminary studies as associated with rejection. We will
then expand our profiling on the Olink platform to include additional panels of proteins reporting on innate and
adaptive immune activation. We will test whether biomarkers provide incremental predictive utility, beyond a
set of prespecified clinical variables. Next, we propose to perform bulk RNA sequencing on peripheral blood
mononuclear cells prospectively collected before transplant & compare differential gene expression of
transcripts related to the protein biomarkers identified between recipients with and without rejection. We will
also perform whole transcriptomic profiling and pathway analysis to identify relevant biological processes
reporting on rejection risk. Finally, we will leverage novel machine learning approaches to identify an integrated
omics signature of rejection risk. The results of the current study will support the submission of future grants to
prospectively evaluate the use of these pre-transplant biomarkers in the clinical care of heart transplant
recipients.

## Key facts

- **NIH application ID:** 10985915
- **Project number:** 1K23HL171828-01A1
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Lauren Kathryn Truby
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $185,579
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10985915

## Citation

> US National Institutes of Health, RePORTER application 10985915, Pre-Transplant Multiomic Profiling to Quantify The Risk of Rejection Following Heart Transplantation (1K23HL171828-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10985915. Licensed CC0.

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