Overview

View the complete and current publication list on Google Scholar 

Greenland JR, Shaver CM, Pandya K, et al. Acute lung allograft dysfunction predicts lung allograft failure: Construct validity of the 2026 International Society for Heart and Lung Transplantation spirometric definition. J Heart Lung Transplant. 2026;45:797–806.
Using 86,885 spirometry measurements from 2,877 recipients across eight centers, this study validated acute lung allograft dysfunction (ALAD) as a clinically meaningful state: ALAD was associated with an approximately five-fold higher hazard of graft failure, while episodes that resolved were not associated with increased subsequent risk. The work provides empirical support for the international ALAD definition and establishes a practical framework for identifying and studying potentially reversible graft dysfunction before established CLAD.
 

Mohanty RP, Calabrese DR, Moghbeli K, et al. Airway molecular signatures in antibody-mediated lung transplant rejection. Am J Transplant. 2026;26:1661–1672.
Small-airway transcriptomics from two transplant centers showed that antibody-mediated rejection (AMR) is associated with airway inflammation, complement activation, and NK-cell pathways, with higher AI2 molecular inflammation scores predicting worse retransplant-free survival. Importantly, the airway response in AMR resembled cellular rejection more than a uniquely humoral molecular state, illustrating how molecular phenotyping can expose biology that conventional diagnostic categories may obscure.
 

Greenland JR, Perch M, Halloran K, et al. Considerations for Endpoints in Lung Transplant Clinical Trials: An ISHLT Consensus Statement. J Heart Lung Transplant. 2026;45:e104–e128.
This international ISHLT consensus effort developed standardized approaches for using PGD, CLAD, acute cellular rejection, AMR, immunosuppression complications, patient-reported outcomes, and other measures as endpoints in lung transplant trials. By linking endpoint definitions to clinical benefit and providing guidance on measurement and adjudication, the statement provides common infrastructure for designing and comparing therapeutic trials in a relatively small and heterogeneous patient population.
 

Brunet-Ratnasingham E, Yellamilli S, Guo R, et al. Persistent and progressive acute lung allograft dysfunction is linked to cell compositional and transcriptional changes in small airways. J Heart Lung Transplant. 2025;44:1482–1492.
Single-cell RNA sequencing of small-airway brushings demonstrated that ALAD with subsequent recovery, persistence, or progression is accompanied by distinct changes in airway cell composition and transcriptional state. The findings provide biological evidence that an episode of physiologic graft dysfunction is not a single entity and support molecular endotyping as a way to distinguish patients likely to recover from those at risk for progression.
 

Pickering H, Arakawa-Hoyt J, Llamas M, et al. Cytomegalovirus-associated CD57+ KLRG1+ CD8+ TEMRA T cells are associated with reduced risk of CMV viremia in kidney transplantation and chronic allograft dysfunction in lung transplantation. Hum Immunol. 2025;86:111285.
Longitudinal immune profiling across lung and kidney transplant recipients identified a CMV-associated population of terminally differentiated CD8 TEMRA cells linked to better viral control and, in lung recipients, reduced risk of chronic allograft dysfunction. The study connects antiviral immune adaptation with graft outcomes and suggests that the consequences of CMV after transplantation depend not simply on viral exposure, but also on the character of the recipient immune response.
 

Mohanty RP, Moghbeli K, Singer JP, et al. Small airway brush gene expression predicts chronic lung allograft dysfunction and mortality. J Heart Lung Transplant. 2024;43:1820–1832.
This multicenter study developed and validated the Airway Inflammation 2 (AI2) gene-expression score, which detected molecular inflammation associated with CLAD even before spirometric diagnosis and predicted graft failure and retransplant-free survival. It established minimally invasive small-airway transcriptomics as a potential platform for detecting biologically active allograft injury earlier than conventional physiologic criteria and for developing molecularly defined treatment strategies.
 

Calabrese DR, Ekstrand CA, Yellamilli S, et al. Macrophage and CD8 T cell discordance are associated with acute lung allograft dysfunction progression. J Heart Lung Transplant. 2024;43:1074–1086.
Single-cell profiling of bronchoalveolar lavage identified an anti-inflammatory macrophage population and activated tissue-resident-like CD8 T cells that distinguished progressive from resolving ALAD; discordance between these populations was associated with an approximately five-fold increased risk of severe graft dysfunction or death. The work helped establish ALAD as a molecularly distinct entity, showed that progression reflects a failure of regulatory immune-cell interactions, and identifies specific cellular relationships that could serve as mechanistic biomarkers or therapeutic targets.
 

Greenland JR, Guo R, Lee S, et al. Short airway telomeres are associated with primary graft dysfunction and chronic lung allograft dysfunction. J Heart Lung Transplant. 2023;42:1700–1709.
Severe primary graft dysfunction was associated with shorter airway epithelial telomeres soon after transplantation, while telomere dysfunction was linked to inflammatory and impaired-remodeling programs and subsequent CLAD. These observations provide a potential biological bridge between an acute peri-transplant injury and chronic graft failure, supporting the concept that early injury can leave durable molecular damage within the transplanted epithelium.
 

Venado A, Kukreja J, Greenland JR. Chronic Lung Allograft Dysfunction. Thorac Surg Clin. 2022;32:231–242.
This review synthesizes the evolving understanding of CLAD as a heterogeneous syndrome encompassing obstructive, restrictive, and mixed phenotypes with different trajectories and outcomes. It places acute rejection, antibody-mediated injury, infection, and primary graft dysfunction within a common framework in which repeated or severe allograft injuries can have lasting consequences that culminate in chronic graft failure.
 

Wang P, Leung J, Lam A, et al. Lung transplant recipients with idiopathic pulmonary fibrosis have impaired alloreactive immune responses. J Heart Lung Transplant. 2022;41:641–653.
Recipients transplanted for idiopathic pulmonary fibrosis demonstrated impaired CD8 T-cell proliferation to donor antigens, with the study examining telomere dysfunction and p53-associated proliferative arrest as potential contributors. The findings challenge the assumption that immune competence is uniform across transplant recipients and connect biological aging and telomere biology to the strength of alloimmune responses.
 

Dugger DT, Calabrese DR, Gao Y, et al. Lung Allograft Epithelium DNA Methylation Age Is Associated With Graft Chronologic Age and Primary Graft Dysfunction. Front Immunol. 2021;12:704172.
Epigenetic profiling of airway epithelial cells showed that the transplanted lung retains molecular information about donor age and that severe primary graft dysfunction is associated with altered biological aging of the airway epithelium. The study extended the concept of allograft aging beyond chronological donor age and provided evidence that transplant-associated injury can become embedded in durable epigenetic states.
 

Calabrese DR, Aminian E, Mallavia B, et al. Natural killer cells activated through NKG2D mediate lung ischemia-reperfusion injury. J Clin Invest. 2021;131:e137047.
Using complementary experimental models and human lung transplant samples, this study demonstrated that NK cells actively mediate ischemia-reperfusion injury through recognition of stress-induced NKG2D ligands on injured pulmonary cells. NK-cell depletion or NKG2D blockade reduced experimental lung injury, moving NK cells from an association with graft inflammation to a causal mechanism and identifying the pathway as a potential therapeutic target.
 

Dugger DT, Fung M, Hays SR, et al. Chronic lung allograft dysfunction small airways reveal a lymphocytic inflammation gene signature. Am J Transplant. 2021;21:362–371.
Small-airway brushings from recipients with CLAD contained a lymphocytic inflammation gene signature associated with graft failure, and airway-brush gene-expression classifiers outperformed those derived from transbronchial biopsies. This work helped establish the small airway as both a biologically important site of chronic rejection and an accessible compartment for molecular diagnosis, laying groundwork for subsequent development of the AI2 platform.
 

Dugger DT, Fung M, Zlock L, et al. Cystic Fibrosis Lung Transplant Recipients Have Suppressed Airway Interferon Responses during Pseudomonas Infection. Cell Rep Med. 2020;1:100055.
Airway epithelial cells from cystic fibrosis transplant recipients showed suppressed interferon responses during Pseudomonas infection, accompanied by differences in DNA methylation, bacterial phenotype, and airway microbial diversity. The study demonstrated that airway epithelial cell programming was linked to clinical phenotypes within lung transplant recipients. It provides a mechanistic example of how recipient disease history can influence the biology of a genetically donor-derived airway after transplantation and helps explain why the same pathogen may have different consequences in different recipients.
 

Calabrese DR, Wang P, Chong T, et al. Dectin-1 genetic deficiency predicts chronic lung allograft dysfunction and death. JCI Insight. 2019;4:e133083.
A loss-of-function variant in CLEC7A, encoding the fungal-recognition receptor Dectin-1, was associated with impaired Dectin-1 expression, greater pathogen burden, and increased graft dysfunction and mortality, with survival findings replicated in the multicenter LTOG cohort. This study leverages one of the largest genomic cohorts in lung transplant and links inherited variation in innate pathogen recognition to long-term transplant outcomes.
 

Calabrese DR, Chong T, Wang A, et al. NKG2C Natural Killer Cells in Bronchoalveolar Lavage Are Associated With Cytomegalovirus Viremia and Poor Outcomes in Lung Allograft Recipients. Transplantation. 2019;103:493–501.
NKG2C+ NK cells expanded within the lung allograft in association with CMV, often increasing before detectable viremia, and higher frequencies were associated with substantially worse CLAD-free survival. The study established a link between CMV-driven NK-cell adaptation and subsequent graft injury, helping motivate a broader program investigating how NK-cell receptor–ligand interactions shape outcomes throughout the life of the lung allograft.
 

Greenland JR, Chong T, Wang AS, et al. Suppressed calcineurin-dependent gene expression identifies lung allograft recipients at increased risk of infection. Am J Transplant. 2018;18:2043–2049.
Functional suppression of calcineurin-dependent cytokine gene expression was associated with airway infection but was not captured by tacrolimus trough concentrations and reflected effects of both calcineurin inhibition and corticosteroids. The work demonstrated the limitations of monitoring immunosuppression solely by drug concentration and advanced the idea that molecular measures of immune function could help quantify an individual recipient's effective state of immunosuppression.
 

Greenland JR, Wong CM, Ahuja R, et al. Donor-Reactive Regulatory T Cell Frequency Increases During Acute Cellular Rejection of Lung Allografts. Transplantation. 2016;100:2090–2098.
Prospective functional assays showed that donor-reactive regulatory T cells are readily detectable after lung transplantation and, contrary to a simple model of failed regulation, increase during episodes of acute cellular rejection. The findings highlighted the complexity of human alloimmunity: regulatory responses can expand alongside effector responses, meaning that the presence of Tregs alone does not necessarily indicate immune tolerance.
 

Greenland JR, Jewell NP, Gottschall M, et al. Bronchoalveolar lavage cell immunophenotyping facilitates diagnosis of lung allograft rejection. Am J Transplant. 2014;14:831–840.
Analysis of nearly 3,000 BAL samples showed that airway immune-cell composition could distinguish rejection from infection and that a multivariable BAL score had a 96–98% negative predictive value for clinically significant acute rejection. The study provided early evidence that information contained within the airway immune compartment can complement tissue histopathology and anticipate future rejection and chronic dysfunction—an idea that subsequently evolved from cellular phenotyping to airway molecular diagnostics.
 

Greenland JR, Jones KD, Hays SR, et al. Association of large-airway lymphocytic bronchitis with bronchiolitis obliterans syndrome. Am J Respir Crit Care Med. 2013;187:417–423.
Lymphocytic inflammation in large-airway biopsies was only weakly related to conventional small-airway or perivascular rejection scores, yet independently predicted subsequent bronchiolitis obliterans syndrome (CLAD). This early study helped establish a central theme: clinically important alloimmune injury is present in the airway, is not fully captured by conventional transbronchial histology, and can contain prognostic information about future chronic graft dysfunction.