# Advancing our Understanding of the Development, Phenotypes, and Progression of Chronic Rejection after Lung Transplantation

> **NIH NIH K23** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $195,826

## Abstract

Project Summary/Abstract
Michael Combs, MD, MS is a Pulmonary and Critical Care physician at the University of Michigan. This K23
proposal outlines the mentored research and training required for Dr. Combs to achieve his long-term goal of
becoming an independent physician-scientist and a leader in understanding the factors which cause and
perpetuate chronic rejection after lung transplantation.
The leading cause of long-term morbidity and mortality after lung transplant is chronic rejection, also called
chronic lung allograft dysfunction (CLAD). Currently, no effective prediction models exist either for 1) the
development of CLAD among healthy lung transplant recipients and 2) survival after CLAD development. This
key research gap limits both clinicians’ ability to personalize care and researchers’ ability to design, power, and
stratify clinical trials. CLAD develops and evolves within a complex interplay of 1) altered lung microbiota, 2)
recipient-derived immune responses, and 3) fibrotic remodeling orchestrated by activated allograft-derived
mesenchymal cells. In previously published studies, Dr. Combs has demonstrated that signals in
bronchoalveolar lavage (BAL) fluid from across these biological domains represent novel risk factors for CLAD
with plausible roles in disease pathogenesis.
In this proposal, Dr. Combs will develop clinical risk prediction models for CLAD development and post-CLAD
survival which integrate patient-specific clinical data and the biological signals in BAL fluid. By completing
these Aims, Dr. Combs will develop new experience and expertise in patient-oriented clinical research,
microbiome-focused computational biology, advanced statistical analysis (including machine learning
approaches), and transplant-focused lung immunology. His training will be supervised by his co-mentors,
Robert Dickson, MD, and Vibha Lama, MD, MS, who have decades of experience and expertise in clinical
research, mentorship of aspiring physician-scientists, and the translational study of lung transplantation, the
lung microbiome (Dr. Dickson), and mesenchymal cell biology (Dr. Lama). His training will further be supported
by an advisory committee with expertise in advanced computational biology and statistical modeling/machine
learning approaches (Susan Murray, ScD) and pulmonary immunology (Bethany Moore, PhD).
Completion of this progressively independent research project will lead to subsequent R03 and R01
applications validating these prediction models of CLAD development and post-CLAD survival in prospective,
multi-center cohorts.

## Key facts

- **NIH application ID:** 10783321
- **Project number:** 1K23HL171904-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Michael Peter Combs
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $195,826
- **Award type:** 1
- **Project period:** 2024-01-01 → 2028-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10783321

## Citation

> US National Institutes of Health, RePORTER application 10783321, Advancing our Understanding of the Development, Phenotypes, and Progression of Chronic Rejection after Lung Transplantation (1K23HL171904-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10783321. Licensed CC0.

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