About

Professor Meghan Rebuli is a faculty member at the University of North Carolina at Chapel Hill within the Curriculum in Toxicology & Environmental Medicine. Her primary research focus is on respiratory immune toxicology, with particular attention to sex differences in this field. She is engaged in clinical and translational research, aiming to bridge laboratory findings with clinical applications. Additionally, Professor Rebuli is involved in the development of airway noninvasive sampling methods, which likely support her research into respiratory health and immune responses. Her work contributes to understanding how environmental factors impact respiratory immune function and how these effects may differ between sexes, advancing knowledge in toxicology and environmental medicine.

Research topics

• Medicine
• Pathology
• Internal medicine
• Immunology
• Biology
• Environmental health
• Political Science
• Pediatrics
• Business
• Cell biology
• Biochemistry
• Psychiatry
• Intensive care medicine
• Family medicine
• Toxicology

Selected publications

• Current Status of Per- and Poly-Fluoroalkyl Substances (PFAS) Exposure on Lung Cell Biology and Pulmonary Outcomes along Human Health Risk Assessment Steps

  Current Allergy and Asthma Reports · 2026-04-25

  articleOpen access

  This review aims to summarize the effects of per- and poly-fluoroalkyl substances (PFAS) exposures on the lung, emphasizing data coverage across steps of human health risk assessments. There is expansive literature characterizing PFAS contamination in water, but recent studies have identified PFAS as a component of air pollution, thus impacts on the lung have been an increasing point of inquiry. Mounting evidence from human clinical/epidemiological, animal, and in vitro investigations supports relationships between PFAS exposures and adverse pulmonary outcomes including asthma, allergies, infections, and cancer. Focusing on toxicology studies using animal and in vitro lung cell models, exposures to PFAS modulated inflammation/immune responses, oxidative stress, mucus production, surfactant properties, and epithelial barrier integrity, representing important mechanisms impacting pulmonary health. There are expanding datasets linking PFAS exposures to adverse pulmonary outcomes; however, these data originated from mostly oral/ingestion exposure and not from volatilized or aerosolized PFAS exposure designs. Furthermore, there is a general lack of data informing dose-response modeling and risk characterization, representing gaps needed to characterize pulmonary health risks.

  PublisherOA PDFDOI

• Prothrombotic Biomarkers Are Not Altered by Wood Smoke: A Pilot Controlled Exposure Study

  UNC Libraries · 2025-07-25

  articleOpen access

  Inhalation of wood smoke (WS) has been associated with increased risk of cardiovascular events, including heart attacks and strokes, both of which are caused in part by the thrombotic occlusion of blood vessels. To characterize the effects of WS on levels of established, circulating prothrombotic biomarkers, healthy human subjects at rest were exposed to WS (500 μg/m3) or filtered air for 2 h. Plasma samples were then used to assess markers of endogenous procoagulant activity: cellular activation (tissue factor-positive extracellular vesicles, TF + EVs), thrombin-antithrombin complexes (TAT), fibrin formation/breakdown (D-dimer), and thrombin generation potential. No significant differences in TF + EVs, TATs, D-dimer, or thrombin generation parameters were detected between WS- or filtered air-exposed individuals. Although females had significantly higher TATs and D-dimers, and slightly but non-significantly shorter thrombin generation lag times than males, there were no significant differences between WS- or air-exposed males or females in any measurements. These data suggest that acute WS exposure does not increase prothrombotic biomarkers in plasma.

  PublisherDOI

• Profiling endogenous airway proteases and antiproteases and modeling proteolytic activation of Influenza HA using in vitro and ex vivo human airway surface liquid samples

  UNC Libraries · 2025-01-29

  articleOpen access

  Imbalance of airway proteases and antiproteases has been implicated in diseases such as COPD and environmental exposures including cigarette smoke and ozone. To initiate infection, endogenous proteases are commandeered by respiratory viruses upon encountering the airway epithelium. The airway proteolytic environment likely contains redundant antiproteases and proteases with diverse catalytic mechanisms, however a proteomic profile of these enzymes and inhibitors in airway samples has not been reported. The objective of this study was to first profile extracellular proteases and antiproteases using human airway epithelial cell cultures and ex vivo nasal epithelial lining fluid (NELF) samples. Secondly, we present an optimized method for probing the proteolytic environment of airway surface liquid samples (in vitro and ex vivo) using fluorogenic peptides modeling the cleavage sites of respiratory viruses. We detected 48 proteases in the apical wash of cultured human nasal epithelial cells (HNECs) (n = 6) and 57 in NELF (n = 13) samples from healthy human subjects using mass-spectrometry based proteomics. Additionally, we detected 29 and 48 antiproteases in the HNEC apical washes and NELF, respectively. We observed large interindividual variability in rate of cleavage of an Influenza H1 peptide in the ex vivo clinical samples. Since protease and antiprotease levels have been found to be altered in the airways of smokers, we compared proteolytic cleavage in ex vivo nasal lavage samples from male/female smokers and non-smokers. There was a statistically significant increase in proteolysis of Influenza H1 in NLF from male smokers compared to female smokers. Furthermore, we measured cleavage of the S1/S2 site of SARS-CoV, SARS-CoV-2, and SARS-CoV-2 Delta peptides in various airway samples, suggesting the method could be used for other viruses of public health relevance. This assay presents a direct and efficient method of evaluating the proteolytic environment of human airway samples in assessment of therapeutic treatment, exposure, or underlying disease.

  PublisherDOI

• Human Sputum Microbiome Composition and Sputum Inflammatory Cell Profiles Are Altered with Controlled Wood Smoke Exposure as a Model for Wildfire Smoke

  American Journal of Respiratory and Critical Care Medicine · 2025-06-13 · 3 citations

  articleOpen accessSenior author

  Abstract Rationale Wood smoke exposure is increasing worldwide because of the increase in wildfire events. Various studies have associated exposure to wildfire-derived smoke with adverse respiratory conditions. However, the mechanism by which this occurs is unknown. Previous studies using wood smoke as a model of wildfire smoke have focused on the respiratory immune response and have reported increased neutrophil percentage and cytokine production in airway samples. The effect of wood smoke on the respiratory microbiome, however, has not been examined. Objectives The objective of this study was to evaluate whether inhaled wood smoke exposure can alter the respiratory microbiome in humans. Methods Healthy volunteers (N = 54) were subjected to controlled wood smoke exposure (500 μg/m3) for 2 hours, and induced sputum samples were collected and processed for microbiome analysis, immune mediators, and cell differentials at baseline and at 6 hours and 24 hours after exposure. A negative binomial mixed model analysis examined associations between microbiome components and inflammatory cells in sputum. Measurements and Main Results After wood smoke exposure, although sputum microbiome diversity remained unchanged, the microbiome composition was altered, particularly the abundance of several low-abundance bacteria, including Fretibacterium and Selenomonas, indicating that this inhalational exposure can alter the composition of the sputum microbiome. In addition, a significant decrease in macrophage cells was observed at 24 hours without a significant change in neutrophils. We further found small but significant associations between different taxa and macrophages (per milligram of sputum), including a negative association with Fretibacterium. Conclusions Together, these findings demonstrate that inhalational wood smoke exposure can modify several low-abundance bacteria within the respiratory microbiome and that these changes are associated with sputum inflammatory cell alterations, providing insights for future studies to focus on respiratory innate immune host–microbiome crosstalk in the context of environmental exposures.

  PublisherOA PDFDOI

• Prothrombotic Biomarkers Are Not Altered by Wood Smoke: A Pilot Controlled Exposure Study

  FASEB BioAdvances · 2025-07-01

  articleOpen access

  ABSTRACT Inhalation of wood smoke (WS) has been associated with increased risk of cardiovascular events, including heart attacks and strokes, both of which are caused in part by the thrombotic occlusion of blood vessels. To characterize the effects of WS on levels of established, circulating prothrombotic biomarkers, healthy human subjects at rest were exposed to WS (500 μg/m 3 ) or filtered air for 2 h. Plasma samples were then used to assess markers of endogenous procoagulant activity: cellular activation (tissue factor‐positive extracellular vesicles, TF + EVs), thrombin‐antithrombin complexes (TAT), fibrin formation/breakdown (D‐dimer), and thrombin generation potential. No significant differences in TF + EVs, TATs, D‐dimer, or thrombin generation parameters were detected between WS‐ or filtered air‐exposed individuals. Although females had significantly higher TATs and D‐dimers, and slightly but non‐significantly shorter thrombin generation lag times than males, there were no significant differences between WS‐ or air‐exposed males or females in any measurements. These data suggest that acute WS exposure does not increase prothrombotic biomarkers in plasma.

  PublisherOA PDFDOI

• IQOS product use in adults who smoke cigarettes daily does not change respiratory inflammatory markers

  medRxiv · 2025-11-19

  preprintOpen accessSenior authorCorresponding

  Introduction: The use and availability of heated tobacco products has increased globally. However, the health effects of IQOS product use remain contradictory, and the impact of IQOS product use on respiratory health and immune biomarkers is lacking. Industry sponsored studies suggest IQOS products reduce exposure to harmful chemicals compared to conventional cigarettes and show attenuated inflammatory responses compared to cigarette smoke, yet independent research studies indicate exposure to IQOS is still associated with negative health outcomes similar to conventional cigarettes. Clinical data is needed to understand the respiratory health impacts of IQOS use in people who currently smoke cigarettes. Methods: Adults located in Los Angeles, California were recruited for the Adult IQOS Respiratory Study (AIRS, N = 32; 21-65 years). Nasal epithelial lining fluid (NELF) and saliva collected from adults who were willing to incorporate IQOS into their daily habits, were analyzed by multiplex enzyme linked immunosorbent assays for 29 different inflammatory markers or cotinine, respectively. Repeated measures ANOVA were used to identify changes in immune markers across the weekly visits. Linear mixed modelling was used to identify changes in participant cigarette or IQOS HeetStick use over the study period. Day was added as a fixed effect. Results: Between-participants variability in IQOS or cigarette usage was identified (p < 0.0001). IQOS and cigarette use did not significantly change across time and remained stable over the course of the 4-week study period. No significant changes were identified in soluble protein mediators across each week. Cotinine concentrations remained consistent, even when disaggregated by sex and visit. Conclusions: All together, these data highlight that dual product use may be more likely in individuals who smoke cigarettes, particularly over the first month of incorporation, rather than completely switching to IQOS products when provided. Furthermore, incorporating IQOS did not significantly change nicotine exposure or nasal inflammatory biomarkers, suggesting, at least with nicotine exposure and nasal inflammation, that addition of heated tobacco products may not substantially reduce harm. What is already known on this topic: Heated tobacco products are marketed as less harmful and smoke-free alternative products compared to conventional cigarettes; however, lack of respiratory data and contradictory reports suggest they may still pose risks and use may contribute to consequential health impacts. Short-term and industry sponsored studies are available, but limited clinical data exists on the respiratory and immunological impacts of IQOS product use. What this study adds: In the follow repeated measures study, our findings provide clinical evidence there are no significant differences in nasal immune biomarkers in individuals that smoke, who incorporate IQOS into their lifestyles. While each participant varied in their IQOS and cigarette product use, no significant trends were observed over the four-week sampling period in overall IQOS or cigarette use. Additionally, when participants were provided with the IQOS option, they were more inclined to dual use both products rather than switch from cigarettes to only IQOS use in the 4 week period studied. How this study might affect research practice or policy: The following clinical study suggests there is an increased likelihood of dual use among individuals who are provided alternative tobacco products. Additional studies should consider evaluating health differences, including immunological markers, between individuals who dual use IQOS and other tobacco products, exclusively use IQOS, people who completely switch their product use and people who quit altogether to establish whether IQOS use reduces harmful exposures resulting in differential inflammatory responses when compared to cigarette use.

  PublisherOA PDFDOI

• Inflammatory Mediator Profiles in the Unchallenged Sinonasal Mucus of Allergic Rhinitis Patients Set to Begin Allergen Immunotherapy

  International Forum of Allergy & Rhinology · 2025-04-04

  articleOpen access

  The authors declare no conflicts of interest Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

  PublisherOA PDFDOI

• Wildfire smoke and respiratory Rx prolonged use in children

  Open MIND · 2025-01-01

  datasetOpen access

  Linked respiratory prescriptions for children, along with information on birth and MSA of birth, and smoke days assigned through pregnancy.

  Publisher

• Respiratory extracellular vesicle isolation optimization through proteomic profiling of equine samples and identification of candidates for cell-of-origin studies

  UNC Libraries · 2025-02-11

  articleOpen access1st authorCorresponding

  Growing evidence supports the importance of extracellular vesicle (EV) as mediators of communication in pathological processes, including those underlying respiratory disease. However, establishing methods for isolating and characterizing EVs remains challenging, particularly for respiratory samples. This study set out to address this challenge by comparing different EV isolation methods and evaluating their impacts on EV yield, markers of purity, and proteomic signatures, utilizing equine/horse bronchoalveolar lavage samples. Horses can serve as effective translational animal models for respiratory studies due to similarities with human immune responses, shared environmental exposures, and naturally occurring respiratory diseases including asthma. Further, horses are long-lived large animals that allow for longitudinal sample collection, and provide large sample volume and cell yield, which are particularly useful since EV research is commonly limited by low sample yields. Here, EVs were isolated from horse bronchoalveolar lavage fluid (BALF) using four different methods (ultracentrifugation, microcentrifugation, and two sizes of size exclusion chromatography columns) and characterized by measuring particle counts, EV purity, total protein yield, and proteomic cargo, with a specific focus on vesicle surface marker expression potentially informing cell type of origin. We found that size exclusion chromatography yielded the highest particle counts, greatest EV purity markers and elevated vesicle surface marker expression. Overall proteomic profiles differed across isolation methods, with size exclusion chromatography clustering separately from centrifugation. Taken together, our results demonstrate that different isolation methods impact characteristics of EVs, notably that size exclusion chromatography, compared to centrifugation methods, resulted in higher EV purity and better characterized proteomic diversity, including information on EV cell-of-origin. This is the first study to characterize proteomic profiles of EVs following different isolation methods using equine BALF. The results of this study will pave the way for future studies using equine and human samples to characterize respiratory tract EVs.

  PublisherDOI

• Noninvasive repeated sampling technique reveals specific respiratory cytokine signatures for electronic-cigarette and dual-product users obtained from a remote cohort of young adults

  medRxiv · 2025-10-24

  preprintOpen accessSenior authorCorresponding

  E-cigarette use has been linked to respiratory mucosal inflammation and other markers of toxicity. Dual use, or the use of e-cigarettes in combination with conventional cigarettes or other inhaled products has increased in prevalence, but there is limited understanding of the health effects associated with dual use. The aim of this study was to establish whether nasal mucosal cytokine profiles among never tobacco users, exclusive electronic cigarette users, and dual tobacco product users change over time and whether dual use significantly differs from exclusive e-cigarette use. This study utilized a repeated sampling study design, collecting nasal epithelial lining fluid from young adult participants (n=64) who were never tobacco users, exclusive electronic cigarette users, and dual tobacco product users, once weekly for four weeks using a remote, non-invasive sampling technique. Nasal mucosal immune mediators and salivary cotinine were then analyzed by ELISA. Differences in mucosal immune mediators were identified between e-cigarette users, dual tobacco product users and never users; however, these markers did not vary across time within group. E-cigarette and dual tobacco product users exhibited increased proinflammatory markers compared to never users. Chemokine profiles were uniquely altered in dual tobacco product users. Sex differences were identified in cytokine and chemokine production across groups. These results suggest that remote, non-invasive nasal sampling is adequate for assessing immune profiles from tobacco product users and cross-sectional sampling is likely representative of consistent respiratory immune profiles across multiple weeks. Dual product use results in distinct respiratory immune profiles, which suggests that long term disease outcomes may differ from exclusive product users. Implications: This study demonstrates that respiratory mucosal immune mediator profiles altered with e-cigarette and other tobacco product use are stable over a period of weeks, suggesting that prior cross-sectional study results likely are representative of effects over longer periods of time. This study also shows that dual use of e-cigarettes with other tobacco products induces a unique elevated chemokine profile compared to sole e-cigarette use, while retaining similar elevated inflammatory cytokine profiles. This suggests that dual product use may induce differential long-term effects that sole product use.

  PublisherOA PDFDOI

Recent grants

• Pre- and Postdoctoral Training in Toxicology

  NIH · $16.6M · 1982–2028

• Impact of sex on respiratory response to wood smoke exposure

  NIH · $457k · 2021–2025

• Woodsmoke-induced disruption of Nasal Microbiome and Cytokine Profiles

  NIH · $422k · 2021–2024

Frequent coauthors

• Ilona Jaspers

  87 shared

• Carole Robinette

  University of North Carolina at Chapel Hill

  21 shared

• Elise Hickman

  University of North Carolina at Chapel Hill

  18 shared

• Stephanie E. Cleland

  16 shared

• Cassandra R. O’Lenick

  15 shared

• Ana G. Rappold

  Environmental Protection Agency

  14 shared

• Mary B. Rice

  11 shared

• Neil E. Alexis

  University of North Carolina at Chapel Hill

  11 shared

Labs

• Curriculum in Toxicology & Environmental MedicinePI

Education

• Ph.D., Toxicology

  University of North Carolina at Chapel Hill

  2007

• M.S., Toxicology

  University of North Carolina at Chapel Hill

  2003

• B.S., Toxicology

  University of North Carolina at Chapel Hill

  2001