# The Clinical and Molecular Impacts of Lung Primary Graft Dysfunction

> **NIH NIH U01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $465,366

## Abstract

Lung Transplantation is a vital therapeutic option for select individuals with end-stage lung disease, however
patient outcomes lag those for other solid organ transplants. The major early complication, primary graft
dysfunction (PGD), refers to acute lung injury occurring in the first 3-days posttransplant. Severe PGD has been
associated with chronic lung allograft dysfunction (CLAD) or chronic rejection, the major limitation to long-term
survival among lung transplant recipients (LTRs). However, the epidemiologic and basic mechanisms that link
severe PGD to CLAD represent a significant knowledge gap in the field. This multi-PI proposal seeks to establish
an NIH Lung Transplant Consortium (LTC) Clinical Center (CC) between Pitt, UCSF and JHU to investigate the
epidemiologic and molecular impacts of severe PGD on acute cellular rejection (ACR) and allograft bacterial
infections, which are both risk factors for CLAD, along with one-year pulmonary function. This proposal tests the
hypothesis that PGD initiates a cycle of hypoxia and inflammation that drives ACR, infection, and impaired lung
function. Using bulk RNA sequencing, we will assess the distal airway transcriptome with airway brush samples
obtained at 3 time points during the first-year post transplant, to determine the molecular pathways by which
severe PGD impacts airway inflammation and pulmonary function. Dr. Merlo will direct Aim 1, which will
determine whether severe PGD grade 3 is a risk-factor for reduced peak FEV1, and increased ACR and allograft
bacterial infections in the first-year. Dr. Greenland will direct Aim 2, which will determine whether severe PGD is
associated with an airway hypoxia gene signature that predicts pulmonary function and infections in the first-
year. Dr. McDyer will direct Aim 3, which will determine whether severe PGD is associated with molecular
evidence of Type-1 inflammation and associated ACR. The multi-PIs have a strong history of collaboration
together, with synergistic expertise in clinical phenotyping of LTRs, transplant immunology, RNAseq analyses
and biostatistics/bioinformatics critical for the success of this project. Each CC site has an established research
program with mature lung transplant registries and biorepositories that include airway brushes and experienced
research coordinators, faculty, and personnel to advance the aims of this study and other LTC projects. This
LTC CC proposal is ideally suited to address both the key knowledge gaps identified above and bring state-of-
the-art capabilities to enhance the productivity of the LTC. Success in this project will advance the epidemiologic
and mechanistic insights into how severe PGD drives peak pulmonary function, and hypoxic and Type-1 immune
responses in the airway transcriptome during the first-year posttransplant. Together, this LTC CC project will
delineate novel biomarkers and key targetable pathways that will contribute to the diagnoses, treatment, and
potential future interventi...

## Key facts

- **NIH application ID:** 10430393
- **Project number:** 1U01HL163294-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** JOHN GREENLAND
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $465,366
- **Award type:** 1
- **Project period:** 2022-08-05 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10430393

## Citation

> US National Institutes of Health, RePORTER application 10430393, The Clinical and Molecular Impacts of Lung Primary Graft Dysfunction (1U01HL163294-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10430393. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*