# Impact of tissue resident memory T cells on chronic rejection after lung transplantation

> **NIH NIH K23** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $172,588

## Abstract

Project Summary / Abstract
This application is for a Mentored Patient-Oriented Research Career Development Award entitled, “The impact
of tissue resident memory T cells on chronic rejection after lung transplantation”, submitted by Dr. Mark
Snyder, an Assistant Professor of Medicine and Immunology within the Division of Pulmonary, Allergy, and
Critical Care Medicine at the University of Pittsburgh, and member of the Starzl Transplantation Institute. The
short-term goals outlined in this submission are designed to help the applicant achieve his long-term objective
of becoming an independent investigator and leader in the field of human lung immunology research. These
short-term goals include (1) advancing knowledge base related to both adaptive and innate immunity, (2)
expansion of both technical and analytic tools required to effectively perform translational immunology
research, and (3) development of leadership skills required to run a productive human immunology laboratory.
The central objective of this research proposal is to investigate the impact of allograft tissue resident memory T
cell (TRM) persistence and generation on the risk of developing bronchiolitis obliterans syndrome, the major
phenotypic presentation of chronic lung allograft dysfunction (CLAD). CLAD affects up to 50% of lung
transplant survivors by 5 years after transplantation and is associated with early mortality and substantial
morbidity. The mechanism of CLAD remains undefined but is believed to be a T cell-mediated process.
Antecedent acute cellular rejection (ACR) and infection, both T cell mediated processes, are associated with
the ultimate development of CLAD. The applicant’s prior work, recently published in Science Immunology,
shows that donor TRM persistence and recipient TRM generation within the lung allograft are associated with
both ACR and infections. Furthermore, unpublished preliminary data show a trend towards early development
of CLAD in those patients with rapid allograft population of recipient TRM. With this proposal, the applicant
expands on this prior work with the following specific aims (1) Define the relationship between recipient TRM
generation in the lung allograft and the risk of early CLAD (within 2 years of transplantation), (2) Determine the
alloreactive potential and pathogen specificity of recipient-derived allograft TRM, and (3) Identify the relationship
between T cell receptor (TCR) clonal diversity and gene expression among recipient allograft TRM and CLAD.
The primary hypothesize is that recipient TRM accumulation will be associated with early-onset CLAD and that
recipient TRM will be composed of an expanded population of T cells with high allo-reactive potential. To
accomplish these aims, the applicant will employ his previously published method of isolating donor and
recipient TRM from the bronchoalveolar lavage of lung transplant recipients longitudinally. Cox-proportional
hazard model, adjusting for known confounders will be perfo...

## Key facts

- **NIH application ID:** 9950145
- **Project number:** 1K23HL151759-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Mark Eugene Snyder
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $172,588
- **Award type:** 1
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9950145

## Citation

> US National Institutes of Health, RePORTER application 9950145, Impact of tissue resident memory T cells on chronic rejection after lung transplantation (1K23HL151759-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9950145. Licensed CC0.

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